$Id: README.versions 120 2010-01-31 19:42:09Z wrp $
 $Revision: 210 $

January, 2010

This directory contains the newest version of FASTA, version 36.
FASTA36 is a major update to FASTA35 that provides the ability to
display multiple significant alignments to a query sequence.  Previous
versions of FASTA displayed only the best alignment between the query
and library sequence; if the library sequence was long, with multiple
similar regions, only the best was shown.  This contrasts with BLAST,
which has always displayed multiple "HSPs" when they are present.

FASTA36 provides some additional improvements; like BLAST, it now uses
statistical estimates to set thresholds for band optimization, which
can increase search speed as much as 2-fold, and it provides much more
flexibility in specifying the files that are searched (indirect files
of filenames can include additional indirection).  But the main
improvement is the display of multiple HSPs.

All of the traditional alignment programs: ssearch36, fasta36,
[t]fast[xy]36 and glsearch36 display multiple HSPs.  The peptide and
mixed peptide alignment programs ([t]fasts36, fastf36, fastm36) still
show a single HSP.

Currently, the PVM/MPI parallel versions of the programs still display
a single HSP.

As of late 2007, there is almost no reason to use the fasta2 programs;
the major programs present in fasta2 that were not present in fasta3
(version 34) -- align (global alignments) and lalign (non-overlapping
local alignments) are now available in fasta version 36.

For more information about the programs in the current FASTA v36
package, see the "changes_v36.html" and "readme.v36" files.

There are still a very few programs in the fasta2 package that are not
available in the fasta3 package - programs for global alignments
without end-gap penalties, the "grease" Kyte-Doolittle plot, and
"garnier" and "chofas" for classic (but inaccurate) secondary
structure prediction. You should not use the fasta2 programs for
library searching; the fasta3 programs are more sensitive and have
better statistics.

Precompiled versions of the programs for Windows and MacOS are available in the
executables directory.

Because of interdependencies in the Makefile, sometimes you must
type "make" a second time to get everything built.

June 12, 1996 - fasta30t1

	Fixed bug in reading blast-format DNA sequence files.
	Fixed core-dump for some large libraries on some machines.

June 19, 1996 - fasta30t2

	Fixed a serious bug in the Smith-Waterman alignment routines used
	by both fasta3 (dropnfa.c) and ssearch3 (dropgsw.c) that caused
	the amount of memory required to depend on the library sequence
	size, rather than the query sequence size.

	Fixed some memory-overwrite errors in showalign.c

June 27, 1996 - fasta30t3

	Found and fixed bugs in comp_thr.c and nxgetaa.c that caused core
	dumps when reading DNA libraries with long sequences in fasta
	format.

July 6, 1996  - fasta30t4

	ibm_pthread_subs.c available, Makefile.ibm for multiprocessor
	IBM RS/6000 AIX systems.

	Finally (?) fixed the previous bug that caused core dumps when
	reading DNA libraries in fasta format.

	Corrections to the fastx algorithm.

July 10, 1996

	Fixed reading of compressed GCG DNA format.

>>August 24, 1996

New programs - tfastx3, tfastx3_t, compare a protein sequence to
forward and reverse translations of a DNA sequence database.  An excellent
replacement for tfasta3.

Sun multiprocessing - change in thr_create() to use all CPU's if available.

GCG formats - now can search with simple GCG-format query sequences and
results with GCG format Swissprot and Genpept are more readable.

>>August 26, 1996

Fixed bugs in tfastx3(_t) and fastx3(_t) including an ancient problem
with aatran().  Less redundancy in gcg_ranlib().


>>August 31, 1996

Included support for BLOSUM62 (-s BL62) as per documentation.

Rearranged Makefile's so that they would make everything in one pass.

>>September 6, 1996

Corrected yet another problem with the fastx/tfastx code.

Noticed that searching without optimized scores gave no optimized
scores on the final list of scores - fixed this.

The pvm version now does alignments - not thoroughly tested.

>>September 13, 1996

Fixed display of best scores to stdout.

Fixed problem with alignments when -o flag used.

pvcompfa/pvcompsw have now been tested on DEC Alpha, Solaris X86, and
SGI PVM implementations.  Several bugs were corrected.

>>September 18, 1996

Fixed bug selectbestz() that caused core dumps in pvcomplib.c
(changes to pvcomplib.c, comp_thr.c, complib.c).

>>September 23, 1996

Corrected showalign.c/pvm_showalign.c addressing bug found and fixed
by Erik Wallin. (erikw@biokemi.su.se).

>>October 15, 1996

Corrected bug so alternative scoring matrices are used.

>>October 22, 1996

Remove singularities from regression routine.

-z 0 now means no statistics (same as -z -1).

No longer show alignment for 0 score.

>>October 26, 1996

Fix problem with -b, -d when Z-values disabled.

>>November 1, 1996

Altschul-Gish statistical estimates (-z 3) now work properly.

Fix problem with mean_var==0.0.

>> October 30, 1996

A new program, sc_to_e, can be used to calculate expectation values
from the regression coefficients reported from a search.  The
expectation value is based on similarity score, sequence length, and
database size.

>> November 8, 1996

fasta30t7 differs from fasta30t6 in the amount of information provided
with the -m 10 option.

(1) The query and library sequence identifiers are no longer abbreviated.

(2) New information about the program and program version are provided:

The new information provided is:

	mp_name: program name (actually argv[0])
	mp_ver: main program version (can be different from function version)
	mp_argv: command line arguments (duplicates argv[0])

    Some statistical information is provided as well:
	mp_extrap: XXXX YYY - statistics extrapolated from XXX to YYY
	mp_stats: indicates type of statistics used for E() value
	mp_KS: Kolmogorov-Smirnoff statistic

The "mp_" (main program) information is function independent, while the "pg_"
information is produced by a particular comparison function (ssearch,
fastx, fasta, etc).  "pg_" should probably be called "fn_", and "mp_"
called "pg_", but I remain backwards compatible.

(3) The end of the "parseable" records is denoted with:

	>>><<<

(4) There now an compile-time option -DM10_CONS, that allows you to
display a final alignment summary:

;al_cons:
     .::.:-   .:: ..  :.    .:.---:   :  .--.:. :
..  .---  ..: :: ... :..: .::.:. .  .---.  .   .:
 : .  . . :    ..   .    :..: .--. . : .:. .. :  .
 .:.:::  ..:. :

or, if M10_CONS_L is defined (in addition to M10_CONS), the output is:
;al_cons:
     p==p=-mmmp==mpzmm=pmmmmz=p---=mmm=mmp--p=zm=m
pzmmp---mmzp=m==mzzzm=zp=mz==z=pmzmmz---pmmpmmmp=m
m=mzmmzmpm=mmmmppmmmpmmmm=pp=mp--pmpm=mp=pmzzm=mmp
mp=z===mmpz=zm=

where '=' indicates identical residues, '-' a gap in one or the other
sequence, 'p' indicates a positive pam value, 'm' indicates a negative
pam value, and 'z' indicates a zero pam value.

A typical run now looks like:

>>>gtm1_mouse.aa, 217 aa vs s library
; mp_name: fasta3_t
; mp_ver: version 3.0t7 November, 1996
; mp_argv: fasta3_t -q -m 10 gtm1_mouse.aa s
; pg_name: FASTA
; pg_ver: 3.06 Sept, 1996
; pg_matrix: BL50
; pg_gap-pen: -12 -2
; pg_ktup: 2
; pg_optcut: 24
; pg_cgap: 36
; mp_extrap: 50000 51933
; mp_stats: Expectation fit: rho(ln(x))= 5.8855+/-0.000527; mu= 1.5386+/- 0.029;  mean_var=73.0398+/-15.283
; mp_KS: 0.0133 (N=29) at  42
>>GTM1_MOUSE GLUTATHIONE S-TRANSFERASE GT8.7 (EC 2.5.1.18) (GST 1-1) (CLASS-MU).
; fa_initn: 1490
; fa_init1: 1490
; fa_opt: 1490
; fa_z-score: 1754.6
; fa_expect:      0
; sw_score: 1490
; sw_ident: 1.000
; sw_overlap: 217
>GTM1_MOUSE ..
; sq_len: 217
; sq_type: p
; al_start: 1
; al_stop: 217
; al_display_start: 1
PMILGYWNVRGLTHPIRMLLEYTDSSYDEKRYTMGDAPDFDRSQWLNEKF
KLGLDFPNLPYLIDGSHKITQSNAILRYLARKHHLDGETEEERIRADIVE
NQVMDTRMQLIMLCYNPDFEKQKPEFLKTIPEKMKLYSEFLGKRPWFAGD
KVTYVDFLAYDILDQYRMFEPKCLDAFPNLRDFLARFEGLKKISAYMKSS
RYIATPIFSKMAHWSNK
>GTM1_MOUSE ..
; sq_len: 217
; sq_type: p
; al_start: 1
; al_stop: 217
; al_display_start: 1
PMILGYWNVRGLTHPIRMLLEYTDSSYDEKRYTMGDAPDFDRSQWLNEKF
KLGLDFPNLPYLIDGSHKITQSNAILRYLARKHHLDGETEEERIRADIVE
NQVMDTRMQLIMLCYNPDFEKQKPEFLKTIPEKMKLYSEFLGKRPWFAGD
KVTYVDFLAYDILDQYRMFEPKCLDAFPNLRDFLARFEGLKKISAYMKSS
RYIATPIFSKMAHWSNK
>>GTM1_RAT GLUTATHIONE S-TRANSFERASE YB1 (EC 2.5.1.18) (CHAIN 3) (CLASS-MU).
; fa_initn: 1406
; fa_init1: 1406
; fa_opt: 1406
; fa_z-score: 1656.3
; fa_expect:      0
; sw_score: 1406
; sw_ident: 0.931
; sw_overlap: 217
>GTM1_MOUSE ..
; sq_len: 217
; sq_type: p
; al_start: 1
; al_stop: 217
; al_display_start: 1
PMILGYWNVRGLTHPIRMLLEYTDSSYDEKRYTMGDAPDFDRSQWLNEKF
KLGLDFPNLPYLIDGSHKITQSNAILRYLARKHHLDGETEEERIRADIVE
NQVMDTRMQLIMLCYNPDFEKQKPEFLKTIPEKMKLYSEFLGKRPWFAGD
KVTYVDFLAYDILDQYRMFEPKCLDAFPNLRDFLARFEGLKKISAYMKSS
RYIATPIFSKMAHWSNK
>GTM1_RAT ..
; sq_len: 217
; sq_type: p
; al_start: 1
; al_stop: 217
; al_display_start: 1
PMILGYWNVRGLTHPIRLLLEYTDSSYEEKRYAMGDAPDYDRSQWLNEKF
KLGLDFPNLPYLIDGSRKITQSNAIMRYLARKHHLCGETEEERIRADIVE
NQVMDNRMQLIMLCYNPDFEKQKPEFLKTIPEKMKLYSEFLGKRPWFAGD
KVTYVDFLAYDILDQYHIFEPKCLDAFPNLKDFLARFEGLKKISAYMKSS
RYLSTPIFSKLAQWSNK
;al_cons:
:::::::::::::::::.:::::::::.::::.::::::.::::::::::
::::::::::::::::.::::::::.::::::::: ::::::::::::::
:::::.::::::::::::::::::::::::::::::::::::::::::::
::::::::::::::::..::::::::::::.:::::::::::::::::::
::..::::::.:.::::
>>><<<


217 residues in 1 query   sequences
18531385 residues in 52205 library sequences
 Tcomplib (4 proc)[version 3.0t7 November, 1996]
 start: Fri Nov  8 18:20:26 1996 done: Fri Nov  8 18:20:41 1996
 Scan time: 38.434 Display time:  2.166

Function used was  FASTA

================================================================

>> November 11, 1996

 --> v30t71

Made changes to complib.c, comp_thr.c, nxgetaa.c to allow scoring
matrix to be modified in fastx3, fastx3_t.

================================================================

>> November 15, 1996

 --> v30t72

nxgetaa.c now accepts query sequences from "stdin" by using "-" as the
input file name.  If DNA sequences are read in this mode, the "-n"
option must be used.

> November 23, 1996

Included code in nxgetaa.c and Makefile.sgi to get around a bug in SGI's
sscanf() that prevented compressed GCG databases from being read properly.

>>November 1, 1997

 --> v31t0

version 31t of the fasta program package uses a more modular
structure for comparison functions.  In addition to modular functions
to initialize, calculate and align sequences, v31 provides a modular
function for creating the alignment display.  This was required for
fasty and fastf, which have very different alignment strategies from
the other search programs.

>>February 13, 1998

modified nascii[] so that 0, 1, 2 are no longer end of sequence
characters.

prss3 added.  Unlike prss, prss3 uses -d # to specify the number of
shuffles.

>>March 18, 1998

First public release.  Corrected problems with dropfz.c (which is
used in fasty3, tfasty3).  Makefile is well tested, but other Makefile's
are not.  PVM versions not tested.

>>March 19, 1998

Problem with unthreaded tfastx3, tfasty3 caused by bug in complib.c
fixed. All Makefiles (Makefile.alpha Makefile.sun, Makefile.sgi,
Makefile.linux) have been tested and work properly. Threaded versions
do not work on linux (yet).  Function labeling problems with fasty3,
tfasty3 corrected.

>>March 20, 1998

 --> v31t02

Fixed problem with inconsistent openlib() calls that broke BLAST databases
on some platforms.

>>March 27, 1998

 --> v31t04

Fixed a long standing problem with fastx/tfastx and fasty/tfasty that
caused various memory allocation problems and core dumps.

The PVM version works again, but cannot produce alignments.  The
change in the location of the modular display functions will require
significant changes in the pvm display functions.  For the moment,
showalign() has been commented out.

Code tested on Macintosh without changes.

Added some additional information in the results file.


Please report bugs to wrp@virginia.edu

>>April 3, 1998

Removed some debugging code in faatran.c now that fastx/fasty bugs
seem corrected.

  FASTA --> v3.14

Corrected uninitialized array elements in dropnfa.c.

>>April 10, 1998

Added facility for specifying SRCH_URL (the URL string that will be
used to re-search the database) and REF_RUL (the URL string that
will be used to lookup the sequence) ini url_subs.c.  This allows perl
scripts to provide different databases for re-searching dynamically.

>>April 16, 1998

 --> v31t05

Corrected problem with ignoring ','s in databases (','s are found in
PIR).

>>April 18, 1998

Corrected some problems with sequence names for Entrez lookups and
re-searching databases.

Made minor modifications to nxgetaa.c and compacc.c for compatibility
with Borland 'C' compiler for Win32 systems.  Including makefile.tc
fasta.rsp, prss.rsp, and test.bat for Borland 'C'/win32.

>>April 24, 1998

 --> v31t06

Fixed another bug in fasty3/tfasty3 alignment routines.

Added additional information to the do_url1() (url_subs.c) function.
The re-search URL can now reference the start, stop, and length of the
library sequence to be re-searched with.  For DNA library sequences,
these values are always in nucleotides, even with tfasta/x/y.


>>May 12, 1998

(no version change as v31t06 was not released prior to this)

Correct nxgetaa.c GETLIB to deal correctly with BLAST NR database
sequences with exceptionally long title lines.

Fix bug with long -O results files.

>>May 18, 1998

 --> v31t07

Corrected some bugs in information string lengths (e.g. gstring1,
stat_str), disabling statistics with -z 0, translation of 'X' by
saatran() (faatran.c) that caused problems with FASTX.

A serious bug has been fixed in the FASTX alignment routines.
For some pathological sequences, % identity increases from < 10%
to 40%. The version number of the main program has not changed,
but the version number of the fastx function has changed to 3.2.

>>June 19, 1998

 --> v31t08

Corrected some problems with alignments with -m 10.

Added -Z db_size option to modify apparent database size for
expectation value calculation (used only for protein/protein FASTA and
SSEARCH, FASTX, FASTY, TFASTX, and TFASTY).

>>July 1, 1998

 (no version change)

Corrected size of lbnames[], lb_size[] in structs.h to accomodate MAX_LF
files.

>>July 13, 1998

 --> v31t09

Corrected problem in nxgetaa.c encountered when reading long sequences
(that must be split) in fasta format.

Corrected problem in statistics calculation encountered with a small number
of very long DNA sequences.

>>July 17, 1998

 (no version change, date change for ssearch3)

Corrected default expectation cutoff (it was 10, now it is 2.0) for
DNA with ssearch3.

>>July 22, 1998

 --> v31t10

Corrected problem with histogram when unscaled statistics used (e.g. prss3).

Corrected problems with prss3 shuffled sequence prompt.  Provided option
to enter number of shuffles, window size, for prss3.  Number of shuffles
for prss3 can be entered as an option (-d #) or as the third argument
on the command line (prss3 query lib 1000).

Modified nrand.c, nrand48.c to use time to set random number.

Corrected problems reading GCG formatted files with prss3.

Corrected various problems with pvcomp* programs, but they still do
not produce alignments with version 3.1.

Two new programs, fastf3(_t) and tfastf3(_t) are available.  These
programs compare a set of mixed peptide sequences from an Edman
sequencer to a protein (fastf3) or DNA (tfastf3) database, using
the database sequences to de-convolve the peptide mixture.

See fastf3.1

>>August 11, 1998

(no version change)

Modified initfa.c so that using '-n' on the fastx/fasty command line
would not cause problems.

Changed labeling of query sequence length for fastx/fasty from 'aa' to 'nt'.

>>August 18, 1998

(no version change)

Modified complib.c, comp_thr.c scaleswn.c, to report E()-value for only
one related sequence if -z 3 is used.

>>August 23, 1998

 -->v31t11

Some serious problems with prss3 have been corrected:

(1) use dropnsw.c rather than dropgsw.c for more accurate low scores

(2) modify estimation program; use scaleswe.c rather than scaleswn.c.
    scaleswe.c has some improvements for estimation by moments and can
    use MLE as well as mu/var (-z 3).

(3) add p() estimate.

(4) correct bugs in nrand48, which caused bad sequences for llgetaa.c

(5) -Z number works properly for prss3 and other programs (fixed histogram).

(6) a new program, ssearch3e, is available that uses the same scaling
    routines as prss3 (scaleswe.c). prss3 will save the random
    sequences it generates when the -r file option is given; the
    sequences are in file_rlib.  ssearch3e (or ssearch3 or fasta) can
    then do a search on exactly the same sequences that were used by prss3.

A bug reading GCG format compressed DNA databases was fixed.

Fixed a bug that caused query sequence not to be displayed with -m 10.

Simple optimization in dropnfa.c improves performance 10%.

>>Sept. 1, 1998

(no version change)

Modified nxgetaa.c to recognize "ACGTX" as nucleotides.

>>Sept. 7, 1998

 --> v31t12

Added -z 11 - 15, which use shuffled sequences, rather than real
sequences to calculate statistical estimates.  Because a shuffled
sequence score is calculated for each sequence score, the search
process takes twice as long.  In this first version, codons are not
preserved during shuffles, so tfasta/x/y shuffles may not be as
informative as they should be.

Also fix a problem with prss3 shuffles.

>>Sept. 14, 1998

 (no version change; previous version not released)

Corrected bugs in tfastx3/tfasty3 caused by using the -3 option with
or without -i.  With the bug fixes; "-3" and "-3 -i" work as expected;
"-3" gives the forward three frames, while "-3 -i" gives the reverse
three frames.

In addition, tfasta3/tfasta3_t was upgraded to perform the same way
that tfastx/y3 does - i.e. a search with "-i -3" searches only frames
4,5, and 6, while "-3" searches only frames 1, 2, and 3.

>>Sept. 29, 1998

 --> v31t13

Corrected bugs in dropfx.c that were corrected in fasta30 last May,
but lingered in fasta31.  Also included code to ensure that tfastx/y
alignments against long introns would not overrun the alignment
buffer.  Instead of overrunning the buffer, the message: ***aligment
truncated *** is displayed.

FASTX/Y and FASTA (DNA) are now half as fast, because the programs now
search both the forward and reverse strands by default.

The documentation in fasta3x.me/fasta3x.doc has been substantially
revised.

>>October 9, 1999
 --> v32t08 (no version number change)

Added "-M low-high" option, where low and high are inclusion limits
for library sequences.  If a library sequence is shorter than "low" or
longer than "high", it will not be considered in the search.  Thus,
"-M 200-250" limits the database search to proteins between 200 and
250 residues in length.  This should be particularly useful for fasts3
and fastf3.  This limit applies only to protein sequences.

Modified scaleswn.c to fall back to maximum likelihood estimates of
lambda, K rather than mean/variance estimates. (This allows MLE
estimation to be used instead of proc_hist_n when a limited range of
scores is examined.)

>>October 20, 1999
(no version change)

Modify nxgetaa.c/nmgetaa.c to recognize 'N' as a possible DNA character.

>>October 9, 1999
 --> v32t08 (no version number change)

Added "-M low-high" option, where low and high are inclusion limits
for library sequences.  If a library sequence is shorter than "low" or
longer than "high", it will not be considered in the search.  Thus,
"-M 200-250" limits the database search to proteins between 200 and
250 residues in length.  This should be particularly useful for fasts3
and fastf3.  -M -500 searches library sequences < 500; -M 200 -
searches sequences > 200. This limit applies only to protein
sequences.

Modified scaleswn.c to fall back to maximum likelihood estimates of
lambda, K rather than mean/variance estimates. (This allows MLE
estimation to be used instead of proc_hist_n when a limited range of
scores is examined.)

>>October 2, 1999
 --> v32t08

Many changes:

(1) memory mapped (mmap()ed) database reading - other database reading fixes
(2) BLAST2 databases supported
(3) true maximum likelihood estimates for Lambda, K
(4) Misc. minor fixes

(1) (Sept. 26 - Oct. 2, 1999) Memory mapped database access.
It is now possible to use mmap()ed access to FASTA format databases,
if the "map_db" program has been used to produce an ".xin" file.  If
USE_MMAP is defined at compile time and a ".xin" file is present, the
".xin" will be used to access sequences directly after the file is
mmap()ed.  On my 4-processor Alpha, this can reduce elapsed time by
50%. It is not quite as efficient as BLAST2 format, but it is close.

Currently, memory mapping is supported for type 0 (FASTA), 5
(PIR/GCG ascii), and 6 (GCG binary).  Memory mapping is used if a
".xin" file is present. ".xin" files are created by the new program
"map_db".  The syntax for "map_db" is:

	map_db [-n] "/dir/database.fa"

which creates the file /dir/database.fa.xin.  Library types can be
included in the filename; thus:

	map_db -n "/gcggenbank/gb_om.seq 6"

would be used for a type 6 GCG binary file.

The ".xin" file must be updated each time the database file changes.
map_db writes the size of the database file into the ".xin" file, so
that if the database file changes, making the ".xin" offset
information invalid, the ".xin" file is not used. "list_db" is
provided to print out the offset information in the ".xin" file.

(Oct 2, 1999) The memory mapping routines have been changed to
allow several files to be memory mapped simultaneously. Indeed, once a
database has been memory mapped, it will not be unmap()ed until the
program finishes.  This fixes a problem under Digital Unix, and should
make re-access to mmap()ed files (as when displaying high scores and
alignments) much more efficient.  If no more memory is available for
mmap()ing, the file will be read using conventional fread/fgets.

(Oct 2, 1999) The names of the database reading functions has been
changed to allow both Blast1.4 and Blast2.0 databases to be read.  In
addition, Makefile.common now includes an option to link both
ncbl_lib.o and ncbl2_lib.o, which provides support for both libraries.
However, Blast1.4 support has not been tested.

The Makefile structure has been improved.  Each architecture specific
Makefile (Makefile.alpha, Makefile.linux, etc) now includes
Makefile.common.  Thus, changes to the program structure should be
correct for all platforms.  "map_db" and "list_db" are not made with
"make all".

The database reading functions in nxgetaa.c can now return a database
length of 0, which indicates that no residues were read.  Previously,
0-length sequences returned a length of 1, which were ignored.
Complib.c and comp_thr.c have changed to accommodate this
modification.  This change was made to ensure that each residue,
including the last, of each sequence is read.

Corrected bug in nxgetaa.c with FASTA format files with very long
(>512 char) definition lines.

(2) (September 20, 1999) BLAST2 format databases supported

This release supports NCBI Blast2.0 format databases, using either
conventional file reading or memory mapped files.  The Blast2.0 format
can be read very efficiently, so there is only a modest improvement in
performance with memory mapping.  The decision to use mmap()'ed files
is made at compile time, by defining USE_MMAP.  My thanks to Eamonn
O'Toole of DEC/Compaq, and Daryl Madura of Sun Microsystems, for
providing mmap()'ed modifications to fasta3.  On my machines, Blast2.0
format reduces search time by about 30%.  At the moment, ambiguous DNA
sequences are not decoded properly.

(3) (September 30, 1999) A new statistical estimation option is
available.  -z 2 has been changed from ln()-scaling, which never
should have been used, to scaling using Maximum Likelihood Estimates
(MLEs) of Lambda and K.  The MLE estimation routines were written by
Aaron Mackey, based on a discussion of MLE estimates of Lambda and K
written by Sean Eddy.  The MLE estimation examines the middle 95% of
scores, if there are fewer than 10000 sequences in the database;
otherwise it excludes (censors) the top 250 scores and the bottom 250
scores.  This approach seems to effectively prevent related sequences
from contaminating the estimation process.  As with -z 1, -z 12 causes
the program to generate a shuffled sequence score for each of the
library sequences; in this case, no censoring is done.  If the
estimation process is reliable, Lambda and K should not vary much with
different queries or query lengths.  Lambda appears not to vary much
with the comparison algorithm, although K does.

(4) Minor changes include fixes to some of the alignment display routines,
individual copies of the pstruct structure for each thread, and some
changes to ensure that every last residue in a library is available
for matching (sometime the last residue could be ignored).  This
version has undergone extensive testing with high-throughput sequences
to confirm that long sequences are read properly.  Problems with
fastf3/fasts3 alignment display have also been addressed.

>>August 26, 1999 (no version change - not released)

Corrected problem in "apam.c" that prevented scoring matrices from
being imported for [t]fasts3/[t]fastf3.

>>August 17, 1999
 --> v32t07

Corrected problem with opt_cut initialization that only appeared
with pvcomp* programs.

Improved calculation of FASTA optcut threshold for DNA sequence
comparison for match scores much less than +5 (e.g. +3).  The previous
optcut theshold was too high when the match penalty was < 4 and
ktup=6; it is now scaled more appropriately.

Optcut thresholds have also been raised slightly for
fastx/y3/tfastx/y3.  This should improve performance with minimal
effects on sensitivity.

>>July 29, 1999
(no version change - date change)

Corrected various uninitialized variables and buffer overruns
detected.

>>July 26, 1999 - new distribution
(no version change - v32t06, previous version not released)

Changed the location of "(reverse complement)" label in tfasta/x/y/s/f
programs.

Statistical calculations for tfasta/x/y in unthreaded version
corrected.  Statistical estimates for threaded and unthreaded versions
of the tfasta/x/y/s/f programs should be much more consistent.

Substantial modifications in alignment coordinate calculation/
presentation.  Minor error in fastx/y/tfastx/y end of alignment
corrected.  Major problems with tfasta alignment coordinates
corrected.  tfasta and tfastx/y coordinates should now be consistent.

Corrected problem with -N 5000 in tfasta/x/y3(_t) searches encountered
with long query sequences.

Updated pthr_subs.c/Makefile.linux to increase the pthreads stacksize
to try to avoid "cannot allocate diagonal arrays" error message.
Pthreads stacksize can be changed with RedHat 6.0, but not RedHat 5.2,
so Makefile.linux uses -DLINUX5 for RedHat5.* (no pthreads stack size).
I am still getting this message, so it has not been completely
successful.  Makefile.linux now uses -DALLOCN0 to avoid this problem,
at some cost in speed.

The pvcomp* programs have been updated to work properly with
forward/reverse DNA searches.  See readme.pvm_3.2.

>>July 7, 1999 - not released
 --> v32t06

Corrected bug in complib.c (fasta3, fastx3, etc) that caused core
dumps with "-o" option.

Corrected a subtle bug in fastx/y/tfastx/y alignment display.

>>June 30, 1999 - new distribution
(no version change)

Corrected doinit.c to allow DNA substitution matrices with -s matrix
option.

Changed ".gbl" files to ".h" files.

>>June 2 - 9, 1999 - new distribution
(no version change)

Added additional DNA lambda/K/H to alt_param.h.  Corrected some
other problems with those table. for the case where (inf,inf)
gap penalties were not included.

Fixed complib.c/comp_thr.c error message to properly report filename
when library file is not found.

Included approximate Lambda/K/H for BL80 in alt_parms.h.
BL80 scoring matrix changed from 1/3 bit to 1/2 bit units.

Included some additional perl files for searchfa.cgi, searchnn.cgi
in the distribution (my-cgi.pl, cgi-lib.pl).

>>May 30, 1999, June 2, 1999 - new distribution
(no version number change)

Added Makefile.NetBSD, if !defined(__NetBSD__) for values.h.  Changed
zs_to_E() and z_to_E() in scaleswn.c to correctly calculate E() value
when only one sequence is compared and -z 3 is used.

>>May 27, 1999
(no version number change)

Corrected bug in alignment numbering on the % identity line
	27.4% identity in 234 aa (101-234:110-243)
for reverse complements with offset coordinates (test.aa:101-250)

>>May 23, 1999
(no version number change)

Correction to Makefile.linux (tgetaa.o : failed to -DTFAST).

>>May 19, 1999
(no version number change)

Minor changes to pvm_showalign.c to allow #define FIRSTNODE 1.
Changes to showsum.c to change off-end reporting.  (Neither of these
changes is likely to affect anyone outside my research group.)

>>May 12, 1999
 --> v32t05

Fixed a serious bug in the fastx3/tfastx3 alignment display which
caused t/fastx3 to produce incorrect alignments (and incorrectly low
percent identities).  The scores were correct, but the alignment
percent identities were too low and the alignments were wrong.

Numbering errors were also corrected in fastx3/tfastx3 and
fasty3/tfasty3 and when partial query sequences were used.

>>May 7, 1999

Fixed a subtle bug in dropgsw.c that caused do_work() to calculate
incorrect Smith-Waterman scores after do_walign() had been called.
This affected only pvcompsw searches with the "-m 9" option.

>>May 5, 1999

Modified showalign.c to provide improved alignment information that
includes explicitly the boundaries of the alignment.  Default
alignments now say:

Smith-Waterman score: 175;  24.645% identity in 211 aa overlap (5:207-7:207)

>>May 3, 1999

Modified nxgetaa.c, showsum.c, showbest.c, manshowun.c to allow a
"not" superfamily annotation for the query sequence only.  The
goal is to be able to specify that certain superfamily numbers be
ignored in some of the search summaries.  Thus, a description line
of the form:

>GT8.7 | 40001 ! 90043 | transl. of pa875.con, 19 to 675

says that GT8.7 belongs to superfamily 40001, but any library
sequences with superfamily number 90043 should be ignored in any
listing or summary of best scores.

In addition, it is now possible to make a fasta3r/prcompfa, which is
the converse of fasta3u/pucompfa. fasta3u reports the highest scoring
unrelated sequences in a search using the superfamily annotation.
fasta3r shows only the scores of related sequences.  This might be
used in combination with the -F e_val option to show the scores
obtained by the most distantly related members of a family.

>>April 25, 1999

 -->v32t04 (not distributed)

Modified nxgetaa.c to remove the dependence of tgetaa.o on TFASTA
(necessary for a more rational Makefile structure).  No code changes.

>>April 19, 1999

Fixed a bug in showalign.c that displayed incorrect alignment coordinates.
(no version number change).

>>April 17, 1999

 --> v32t03

A serious bug in DNA alignments when the sequence has been broken into
multiple segments that was introduced in version fasta32 has been
fixed.  In addition, several minor problems with -z 3 statistics on
DNA sequences were fixed.

Added -m 9 option, which unfortunately does different things in
pvcompfa/sw and fasta3/ssearch3.  In both programs, -m 9 provides the
id's of the two sequences, length, E(), %_ident, and start and end of
the alignment in both sequences.  pvcompfa/sw provides this
information with the list of high scoring sequences.  fasta3/ssearch3
provides the information in lieu of an alignment.

>>March 18, 1999

 --> v32t02

Added information on the algorithm/parameter description line to
report the range of the pam matrices.  Useful for matrices like
MD_10, _20, and _40 which require much higher gap penalties.

>>March 13, 1999 (not distributed)

 --> v32t01

 -r results.file  has been changed to -R results.file to accomodate
 DNA match/mismatch penalties of the form: -r "+1/-3".

>>February 10, 1999

Modify functions in scalesw*.c to prevent underflow after exp() on
Alpha Linux machines.  The Alpha/LINUX gcc compiler is buggy and
doesn't behave properly with "denormalized" numbers, so "gcc -g -m
ieee" is recommended.

Add "Display alignments also (y/n)[n] "

pvcomplib.c again provides alignments!!  In addition, there is a
new "-m 9" option, which reports alignments as:

>>>/home/wrp/slib/hlibs/hum0.aa#5>HS5 gi:1280326 T-cell receptor beta chain 30 aa, 30 aa vs /home/wrp/slib/hlibs/hum0.seg library
HS5         	  30	HS5         	  30	1.873e-11	1.000	  30	   1	  30	   1	  30
HS5         	  30	HS2249      	  40	1.061e-07	0.774	  31	   1	  30	   7	  37
HS5         	  30	HS2221      	  38	1.207e-07	0.833	  30	   1	  30	   7	  35
HS5         	  30	HS2283      	  40	1.455e-07	0.774	  31	   1	  30	   7	  37
HS5         	  30	HS2239      	  38	1.939e-07	0.800	  30	   1	  30	   7	  35

where the columns are:

query-name      q-len   lib-name      lib-len   E()             %id    align-len  q-start q-end   l-start l-end

>>February 9, 1999

Corrected bug in showalign.c that offset reverse complement alignments
by one.

>>Febrary 2, 1999

Changed the formatting slightly in showbest.c to have columns line up better.

>>January 11, 1999

Corrected some bugs introduced into fastf3(_t) in the previous version.

>>December 28, 1998

Corrected various problems in dropfz.c affecting alignment scores
and coordinates.

Introduced a new program, fasts3(_t), for searching with peptide
sequences.

>>November 11, 1998

  --> v32t0

Added code to correct problems with coordinate number in long library
sequences with tfastx/tfasty.  With this release, sequences should be
numbered properly, and sequence numbers count down with reverse
complement library sequences.

In addition, with this release, fastx/y and tfastx/y translated
protein alignments are numbered as nucleotides (increasing by 3,
labels every 30 nucleotides) rather than codons.

  $Id: readme.v33t0 342 2010-06-28 19:57:56Z wrp $
  $Revision: $

================ readme.v33t0 ================

This release includes an MPI implementation of the parallel
library-vs-library comparison code.  See readme.mpi_3.3 and
readme.pvm_3.3 for more information.

=====
>>July 9, 2001

Considerable changes to support no-global library functions.

(1) Separate ascii/sequence mapping arrays are used by the
    query-reading (qascii), library-reading (lascii), and sequence
    comparison function (pascii) routines.  As a result, there is no
    longer a need for tgetlib.o/lgetlib.o - lgetlib.o can serve both
    functions.

(2) This also allows us to remove all #ifdef TFAST/FASTX conditionals
    from complib.c/comp_thr.c/p2_complib.c.  We no longer need
    tcomp_thr.o, comp_thrx.o, etc.  We still have a variety of
    p2_complib.o variations to support the different c34.work* files.

(3) Because non-global openlib/getlib functions are available, exactly
    the same open/get functions are available for reading both the
    query and reference libraries in pv34comp* programs.  The
    host-specific openlib/getlib functions in hxgetaa.c are now
    provided by nmgetlib.c, etc. This has two effect:

    (a) it is now possible to compare a query database generated by an
        SQL query to a library database generated by a different SQL
        query.

    (b) pv34comp* has lost (at least in this version) the ability to
        automatically detect the query sequence type. To search with a
        DNA query, you MUST use "-n".

(4) the resetp() function is now responsible for almost all of the
    function sepcific (TFAST/FASTX/etc) initializations.  All of the
    function specific code has been removed from complib.c/comp_thr.c
    and most of it has been moved to initfa.c/resetp().

(5) manageacc.c has been merged into compacc.c (mostly prhist()).

(6) Although it may reflect a subtle bug in my code, it is not
    possible to reliably run threaded/memory mapped versions of the
    fasta34_t code.  I have spent considerable time tracking down the
    problem, and have determined that, in threaded code, something
    happens during the thread initialization to corrupt the
    description offset information used when files are memory mapped.
    This never occurs when the unthreaded versions of the code are
    used.  And it does not occur under MacOSX, Compaq Tru64Unix, Sun
    Solaris/Sparc, or SGI IRIX.

    Thus, I cannot recommend using the threaded code versions (_t)
    under Linux (RH6.2 or 7.1).

=====
>>June 1, 2001

Many changes to accomodate a new - no global variable - strategy for
reading sequence databases.  Every time a file is opened, a struct
lmf_str is allocated which can be used for memory mapped files, ncbl2,
files, and mysql files.

In addition, an open'ed file has a default sequence type: DNA or
protein, or one can open a file in a mode that will allow the sequence
type to be changed.

=====
>>May 18, 2001		CVS: fa33t09d0

A new compile time parameter - -DGAP_OPEN, is available to change the
definition of the "-f gap-open" parameter from the penalty for the
first residue in a gap to a true gap-open penalty, as is used in BLAST
and many other comparison algorithms.  This will probably become the
default for fasta in version 3.4.

Fixes to conflicts between "-S" and "-s matrix".  When a scoring
matrix file was specified, lower-case alignments were not displayed
with -S (although the scores were calculated properly).

More extensive testting of mysql_lib.c (mySQL query-libraries) with
the pv4comp* and mp4comp* programs.

=====
>>April 5, 2001		CVS: fa33t08d4b3

Changes in nmgetlib.c and ncbl2_mlib.c to return long sequence
descriptions for PCOMPLIB (pv4/mp3comp*).  Also fix p2_complib.c to
request DNA library for translated comparisons.

Fix for prss33(_t) to read both sequences from stdin.

=====
>>March 27, 2001	CVS: fa33t08d4
 --> fa33t08d4

Problems in ncbl2_mlib.c found searching NCBI non-redundant nucleotide
database "nt" were fixed.  Testing revealed a minor memory leak, which
was fixed by modifying showbest.c, showalign.c, comp_thr.c, complib.c,
and p2_complib.c to remember the last opened database file more
effectively.

Modifications to allow 64-bit fseek/ftell on machines like Sun,
Linux/Intel, that support -D_FILE_OFFSET_BITS=64, -D_LARGE_FILE_SOURCE
off_t, and fseeko(), ftello() with the option -DUSE_FSEEKO.  Machines
with 64-bit long's do not need this option.  Machines with 32-bit
longs that allow files >2 Gb can do so with 64-bit file access
functions, including fseeko() and ftello(), which work with off_t file
offsets instead of long's.

=====
>>March 3, 2001		CVS: fa33t08d2

Corrected problems in nmgetaa.c and mysql_lib.c with parallel
programs, and one serious problem with alternate DNA scoring matrices
(initfa.c, initsw.c) not being set properly.  A subtle problem with
the merge of scaleswn.c and scaleswg.c is fixed.

>>February 17, 2001

Modified mysql_lib.c to use "#", rather than "%ld", to indicate the
position of the GID.  This change was made because sprintf() cannot be
used reliably to generate an SQL string, as '"' and '%' are used in
such strings.

=====
>>January 17, 2001
(no version change, date change)

Minro fixes to initfa.c, initsw.c to deal with DNA scoring matrices
properly. "-n -s dna.mat" is required for the sequence/matrix to be
recognized as DNA.

>>January 16, 2001
-->v34t00

Merge of the main CVS trunk - fa33t06 with the latest release branch,
fa33t08.

In addition, PCOMPLIB mods have been made to mysql_lib.c.  Because
p2_complib.c gets sequence description information during the first
read of the database, the mysql_query must be changed to return:
result[0]=GID, result[1]=description, result[2]=sequence.  In the
PCOMPLIB case, the other SQL queries (for GID description, sequence)
are not necessary but must still be provided.

=====
>>January 16, 2001
(no version change, previous version not released)

changes to p2_complib.c to correct openlib() incompatibility.

changes to nmgetaa.c, ncbl2_lib.c to incorporate PCOMPLIB.  nxgetaa.c
removed.

=====
>>January 12, 2001
(no version change, previous version not released)

Change to initfa.c to move ktup check from query_parm() to last_init().

=====
>>January 10, 2001
--> v33t08

Fixes to complib.c, comp_thr.c to deal properly with long query
protein sequences when a short library chunk (e.g. -N 5000) was given.
In the case where the chunk size is too short, it will be reset to a
length which allows the search to proceed, by including an amount of
new sequence that is equal to the amount of overlap sequence.

scaleswn.c and scaleswg.c have been merged.

v33t08 includes the initial implementation for mySQL described below
for v33t07x.

======
>>Dec. 20, 2000
--> v33t07x

Initial implementation of a syntax for mySQL database queries.  A new
file, mysql_lib.c has been added, and changes have been made to
nmgetaa.c (which should now replace nxgetaa.c) and altlib.h.  A mySQL
database search needs a file with 4 parts:

(1) description of the database, user, password
(2) a select statement that generates the set of protein sequences
    as: UID, sequence
(3) a select statement that generates a UID, description given a UID
(4) a select statement that generats a single UID, sequence given a UID

Each of the four parts should be separated by ';'.  For example, in
the database that we are using for testing, a file "demo.sql" that
contains:

================
localhost taxonomy username secret;
SELECT proteins.gid, proteins.sequence FROM proteins,swissprot WHERE proteins.gid=swissprot.gid AND swissprot.spid IS NOT NULL;
select proteins.gid, concat(swissprot.spid," ",proteins.description) from proteins,swissprot where proteins.gid=%ld AND swissprot.gid=proteins.gid;
select gid, sequence from proteins where gid=%ld;
================

will find all the proteins in the BLAST "nr" database that also have
SwissProt ID's when given the command line:

	fasta33 -q query.aa "demo.sql 16"

At least for simple queries, there is surprisingly little overhead for the
search.  For more complex queries involving several tables, the overhead
can be significant.

At the moment, libraries that need the functions in mysql_lib.c will
use library type 16.  We may also use file type 17 for SQL queries
that return binary sequences.

This implementation of mysql_lib.c was written to require a minimal
amount of change to the other programs.  Only nmgetaa.c and altlib.h
needed to be changed to incorporate this new capability.  One result
of this limitation is that one cannot mix mySQL databases queries with
other databases in the same search.  Eventually, I would like to make
a mySQL database like any other, so that several mysql database
queries could be searched in the same run, and mysql databases could
be mixed with other (flat file) databases, but this will require some
changes in the function calls throughout the code.  (Right now, the
various programs do not distinguish between an openlib() that is made
before searching a large database, and one before retrieving a single
sequence.  This must be changed for a database query like mySQL to
behave like other databases.

Several mySQL demo files have been provided: mysql_demo*.sql.

(10 January 2001) The mySQL code has been tested on Intel Linux and
Compaq/Alpha/Tru64 Unix.

>>Dec. 9, 2000

Changes to apam.c that to tie different default gap penalties to
alternate scoring matrices.  In addition, changes to apam.c, to deal
with user-specified matrices with or without '*'.

>>Nov. 5, 2000 (date updated)

pst.dnaseq can now have 3 values, -1, or 0-> protein, 1->DNA, and 2->other.
This becomes important for thing like init_karlin_a, which needs a
background frequency of residues.

>>Nov. 1, 2000

Significant bug fixes for the -z 6/-z 16 option.  An ininitialized
variable was fixed in karlin.c, and comp_thr.c did not pass the
correct composition argument type in find_zp().  The -z 6/16 option
has now been tested and works correctly on Alphas, Linux x86, SGI, Sun
and Mac OSX. Another problem was fixed in scaleswn.c (simplex()) that
prevented the code from being reused by the pv4/mp4 complib programs.

>>Oct. 9, 2000

Several changes made to accomodate Mac OSX.  Longer lists of superfamily
numbers now supported in p[su]4comp/m[su]4comp programs.

>>Sept 25, 2000

All global variables have been removed from scaleswn.c. The last to
go, db_struct db, required many edits, because until now, the fasta
programs have kept two versions of the db_struct data (entries,
length). One version was kept by the main program, which updated entry
number and db length as sequences were read; a second copy of this
information was kept by the statistical estimation routines.  Now
there is only one copy, which means that the E() values will be a
function of the complete database, not the database with some high
scoring sequences removed.

>>Sept 23, 2000

Continued removal of global variables from scaleswn.c.  Only one
global is left, db_struct db, which contains the number of entries in
the database and the number of residues.  It will be the next to go
(changing all the zs_to_*() functions) and scaleswn. will be free
of globals.  scaleswg.c is gone - scaleswn.c compiles to scaleswg.c
with -DNORMAL_DIST.

>>Sept 20, 2000

Removal of histogram globals required changes in p2_complib.c as well.
p_complib.c has not been updated.  scaleswg.c has been modified to
reflect the new histogram strategy.

>>Sept 19, 2000

Substantial changes to remove globals for printing histogram.  m_msg
now contains a hist_str, which keeps histogram information.

>>Sept. 19, 2000
(no version change, previous version not released)

Correct bug introduced into scaleswn.c (inithist()) by changing
score2_sums[], score_sums[] from int to double.

Reporting of version numbers is more consistent between fasta33,
fasta33_t, and pv4compfa/mp4compfa.  The programs now report the same
numbers/dates in similar places.

>>Sept. 15, 2000
--> v33t07

Changes to fix problems with statistical estimates when a large
fraction (but not all) of the database is related.  Several users
reported problems when searching with rRNA genes with version 33t06.
In some cases, a 100% identitical match over 1500 nt would not be
statistically significant against a search of the bacterial division
of Genbank.  This problem was not seen with some releases of v33t05.

The cause of the problem was a change between v33t05 and v33t06 to
allow scoring matrices with unusual scaling to be used.  In v33t05,
there was a line that excluded all scores > 300 from the statistical
estimation procedure.  While 300 is a high score with any "normal"
scoring matrix, some investigators were using matrices scaled 10X, so
that a score of 300 was really a score of 30 with a conventional
matrix, and should not be excluded.  Unfortunately, removing the test
to exclude scores > 300 meant that when a rRNA sequence was used to
search the bacterial division, tens of thousands of high scoring
related sequences were treated as if they were unrelated, with the
result that the variance estimates were much too high, and thus high
real scores had low z-scores, and thus were not statistically
significant.  (There appear to be more than 20,000 rRNA sequences in
the bacterial division of Genbank, almost 25% of all sequences).

The solution to the problem is a substantial enhancement in the
strategies used to exclude high-scoring, related sequences, the -z 1,
4, and 5 parameter estimation strategies.  The programs now estimate
the expected high scoring sequence by calculating an ungapped Lambda
and K, and then use a relatively conservative threshold for excluding
scores that are higher than would be expected 0.01 times by chance.
By calculating Lambda and K, we can scale the cutoff thresholds to
allow scoring matrices with unusual scales.  For "normal" searches,
there should be little change, but there should be an improvement for
searches with large numbers of related sequences in the database.

As a result of testing for this change, a bug in the karlin() function
used with -z 6 was found and corrected.

=======
>>Sept. 9, 2000

Changes to manshowbest.c to include correct display coordinates.

Significant changes to structs.h, param.h, p2_complib.c,
p2_workcomp.c, to store and use a reliable a_struct for alignment
coordinates.

Other cosmetic changes.

>>Sept. 7, 2000

Minor changes to complib.c, showrss.c, so that prss33 -q uses 200
shuffles and prss33 provides bit scores, rather than z-scores.
(no version number change).

Modifications to p2_complib.c to include superfamily numbers for
ps4comp* ms4comp*.

>>Aug 22, 2000

Changes to mmgetaa.c, ncbl2_mlib.c, dropfs.c to accomodate AIX.
00README.1st updated to reflect the current version and correct
outdated information on threads.

>>Aug. 3, 2000

Modifications to initpam2() in initsw.c to correct a problem with pam_x
when the -S option is used.

Modifications to compacc.c, scaleswn.c to ensure that residue numbers
are calculated properly when more than 2 Gb of sequence is searched.

>>July 12, 2000

Modifications to dropnfa.c so that DNA matches to 'N' will be included
in the "ungapped %identity".  Thus, a sequence that is 100% identical
for 100 nt on either side of a 100 nt region that has been masked to
'NNNNN' will be reported as: "67% identical (100% ungapped)".  This
has been added to deal with masked BAC-end databases.  It would be
better if masking changed the letters to lowercase, but the mouse
BAC-end sequences at TIGR use 'NNNNN'.  This is currently available
only for the fasta function, not [t]fast[x/y], etc, and only for DNA
sequences.

mk_n_pam() in apam.c modified to ensure that mismatch scores of -1
remain -1.

>>June 25, 2000

Modification to nxgetaa.c, nmgetaa.c, mmgetaa.c to return Genbank Accession
number as part of the descriptive string.

>>June 11, 2000

(no version change - not yet released)

Modifications to calcons(), calc_id(), showbest(), p_workcomp.c to
provide ngap_q (number of alignment gaps in query) , ngap_l (number
of gaps in library) information for -m 9 output.

>>June 6, 2000

(no version change - not yet released)

Modified scaleswn.c to provide better support for unconventional
scoring scoring matrices, in particular, scoring matrices where every
value is 50-times higher.  Previous versions of the MLE estimator (-z
2) started with lambda = 0.2, which is too high for a scoring matrix
going from -500:+1500. The initial estimate for lambda is now
calculated using the formula: lambda = pi/sqrt(6*variance).  For the
default -z 1, a restriction to limit scores to a maximum of 300 for
the statistical analysis was removed.

>>June 3, 2000

Modified aligment output, and -m 9 and -m10, to report an "ungapped"
identity as well as the traditional "gapped" identity.  The
traditional "gapped" identity reports the number of identities divided
by the overall length of the alignment, including gaps.  The
"ungapped" identity does not include gaps in the length of the
alignment.  This new value is included for alignments that include
introns; thus, a tfastx33 search might find the 100% identical genomic
sequence but report the gapped percent identity if a short intron were
included in the alignment (the alignment probably would not span a
long exon) as 66%.  The "ungapped" identity would remain 100%.  The
ungapped identity value is also shown in the "-m 9" output line after
the "gapped" fraction identical.

>>June 1, 2000

Modified -m 9 output to provide fraction identical, alignment boundary
information with the initial list of high scoring sequences, just as
the pv3comp and mp_comp versions do.  The -m 9 option now shows the
same alignment display as -m 0, but the width of the alignment is
increased by 40.  Thus, by default, -m 9 will show the list of best
hits, with percent identity, Smith-Waterman score, and alignment
boundaries initially, and then show alignments standard (-m 0)
alignments with 100 residues/line.

>>May 29, 2000

Correct some problems with reading data files with <CR>'s under unix.

nmgetaa.c/nxgetaa.c/mmgetaa.c have been modified to convert <TAB>
('\t') to <SPC> (' ') in descriptive lines.

=======

>>May 3, 2000

  Corrected problem with very low mean_var in fit_llen() in scaleswn.c.

>>May 2, 2000
  (no version number change - previous version not released)

  Merged fasta33t05d2 with fasta33t06.  Also removed restriction on
"-M size-range" to proteins - the size range now can be applied to DNA
as well.

>>May 1, 2000
 (changes to v33t05d merged into v33t06)

Introduced changes to include '*' as a valid sequence character, which
indicates termination.  Thus, 'TGA', 'TAG', and 'TAA' are now
tranlated to '*' rather than 'X', and the protein PAM matrices have
been modified to provide a match score of approximately 1/2 the max
identity score for a '*:*' match.  Otherise, '*' is the same as 'X'.
This change only affects query sequences that include a '*' to
indicate an end of sequence, the '*' is not there by default.

The inclusion of '*' broke some things in tfasts33, tfastf33, fasty33,
and tfasty33, which were fixed today.

>>March 28, 2000/April 24, 2000
 --> v33t06

(a) -z 6 statistics that factor in composition
(b) -smatrix-offset pam-offset parameter

(a) This release provides a new statistics option, -z 6, which
provides a more sophisticated model that accounts for sequence
composition.  When -z 6 is used (only for fasta33(_t) and
ssearch33(_t)), the program calculates a composition parameter
comp=1/lambda using a modified version of the Karlin-Altschul karlin()
function.  As a result, every sequence in the database has an
associated length (n1) and composition (comp).

The length n1 and composition comp are used in the maximum likelihood
estimation described by Mott (1992) Bull. Math. Biol. 54:59-75.  Four
parameters are estimated, a0, a1, a2, and b1, and the probability of
obtaining a score is then:

p(s >= x) = 1-exp(-exp(-( a0 + a1*comp + a2*comp*log(n0*n1) + x)/(b1*comp)))

The maximum likelihood estimates of a0, a1, a2, and b1 are calculated
using the Nelder-Mead simplex search strategy.

The average Lambda is reported for the search using Lambda =
1/(b1*ave_comp).  Where ave_comp is the geometric mean of the comp values
calculated during the statistical estimates.

The "lambda/comp" calculation can fail for sequences with very biased
amino acid composition.  When this occurs, 'comp' is set to -1.0 (as
is 'H', the information content parameter) and the 'ave_comp' value is
used to calculate statistical significance.  (But obviously 'ave_comp'
is not really appropriate, since if the sequence had an average 'comp'
value, it would have been calculated.)  When -z 6 is used, the
alignment display shows the 'comp' and 'H' values for that library
sequence.

(b) Scoring matrix offsets - The main reason that the "lamdba/comp"
calculation fails is that, for the particular query/library sequence
pair, the expected score is not < 0, instead, Sum {p_ij S_ij} >= 0.0.
This problem is reported to 'stderr' when it occurs.  The simplest
solution to the problem is to provide an offset to the scoring matrix;
for example, to use Blosum62 - 1, which ranges from +10 to -5, rather
than the standard +11 to -4.  This option used to be available with
the -S offset option, but -S is now used to specify a lower-case
seg-ed database.  The offset can now be specified as part of the
scoring matrix name.  Thus, "-s BL62-1" uses Blosum62 reduced by 1 at
each entry.  The '-' character is used to indicate an offset, so
scoring matrix files must not have a '-' in their name.
Alternatively, "-s BL80+1" or "-s BL80--1" would add one to each value.

nxgetaa.c, nmgetaa.c, and mmgetaa.c have been edited to avoid string
run-off problems after strncpy().

Fixed problem where positive gap extension penalties in ssearch33
were not converted to negative values.

>>April 8, 2000

Fixed problem in calculating corrected sequence lengths for
Altschul-Gish probabilities.

>>March 30, 2000
  (no version change, date updated to March 30, 2000)

Corrected problem with -m 9 option.

The '*' character is now available to allow translated alignments to
extend through the termination codon. Thus, if a protein sequence ends
with a '*', and matches in to a translated termination codon, the
score will be increased.  The *:* match score is set to 1/2 the max
positive score for the matrix (see upam.h).  This strategy can also be
used to upweight a match that extends all the way to the end of a
full-length sequence by putting '*' at the end of both the query and
library protein sequences.  Recognition of '*' will probably become a
command line option.

>>March 21, 2000
  (no version change, previous version not distributed)

Changes to map_db.c, list_db.c, and mmgetaa.c to accomodate large
sequence files.  Long (64-bit on some systems) variables are now used
to specify file and memory position for the memory mapped functions.
As a result, there are now two *.xin (memory mapped index) file
formats: MP0, which uses 32-bit longs, and MP1, which uses 64-bit
longs. On 64-bit machines, MP0 32-bit indices are read properly, but
limit the database size to 2 or 4 Gb; MP1 64-bit indices allow very
large databases.  Blast2.0 formatdb databases are still limited to
4Gb.  To compile map_db.c to generate 64-bit index files, include the
compile time option -DBIG_LIB64 in the Makefile.  (Currently this
option has been tested only on the DEC Alpha and SGI platforms, and
will work only with Unix versions that provide 64-bit longs and 64-bit
ftell()'s.)

The -R results file now uses sfn_cmp() to report a matching
superfamily number, if one exists, and '0' otherwise.

>>March 12, 2000
  (no version change, previous version not distributed)

Provide new strategy for specifying library abbreviations.  In
addition to:

	fasta33 query.aa %anr

one can also specify:

	fasta33 query.aa %pir1+sp+nr
or
	fasta33 query.aa +pir1+sp+nr
or
	fasta33 query.aa %+pir1+sp+nr

where the + anywhere in the library name string indicates that
variable length library names, separated by '+', are being used (the
last '+' is optional).  The FASTLIBS file then becomes:

================
PIR1 Annotated Protein Database (rel 56)$0+pir1+/slib2/blast/pir1.lseg
NBRF Protein database (complete)$0+nbrf+@/seqlib/lib/NBRF.nam
NRL_3d structure database$0D/seqlib/lib/nrl_3d.seq 5
NCBI/Blast non-redundant proteins$0+nr+/slib2/blast/nr.lseg
NCBI/Blast Swissprot$0+sp+/slib2/blast/swissprot.lseg
================

The two abbreviation types, single letter and +word+, cannot be
intermixed, and at least initially, +word+ specifiers are
case-sensitive (single letter abbreviations are not) and will not be
available interactively, only on the command line.

Removed 'K' estimate for Expectation_n, Expectation_i fits to the
distribution of unrelated similarity scores.  'K' cannot be calculated
from the data available.  'Lamdba' can be calculated, it is
1.28255/sqrt(mean_var), and is still available.

>>March 3, 2000
 (no version change)

changed Makefile33.common, Makefile.common, to incorporate $(NRAND)
rather than "rand48".  Provide nrandom.c which uses random(), as
replacement for nrand.c, which uses rand48().

>>February 8, 2000
  --> v33t05

Fixes to scaleswn.c (proc_hist_ml) to set num_db_entries properly.
Scaleswn.c also provides Lambda estimates for -z 1/11 (Expectation_n),
and -z 1/14 (Expectation_i) statistical estimates.

Modifications to calc_id() to correct bug in counting identities.
Modified showalign() to use calc_id() with -m 9, for simpler
debugging.

Additional modifications to dropfa*.c files to deal properly with 'n's
and 'x's.

Added new option: -x #, which allows one to override the penalty for a
match against 'x' (or 'N') provided by the scoring matrix.  This
option is particularly useful in fast[x/y] searches, where out of
frame low complexity regions can generate high scores.

The old function of '-x' - to specify an alternate coordinate system,
is now available as '-X # #'.

Updated scaleswn.c to provide window shuffle information for -z 12.

Updated compacc.c, workacc.c, to fix serious bug in wshuffle()
that destroyed aa1[n1]=0.

>>January 25, 2000
  --> v33t04

  A serious bug in all of the fasta related programs has been
corrected.  The new code in fasta33 which ignores certain residues
failed to initialize one of the arrays properly.  As a result, in
pathological situations, a very strong match could be missed.

  Corrected minor bug in initsw.c that cause misplaced "ktup" command
line argument, which should be ingnored by ssearch, to be read as -d
ktup.

  Improved error message for 0 length query sequence.

>>January 17, 2000
  --> no external version number change

Modified mmgetaa.c, map_db.c, and nmgetaa.c to provide memory mapping
of genbank flatfile (format=1) files.  This format could be read much
more efficiently, however.

>>January 12, 2000
  --> no external version number change

Changed the behavior of the options that set the number of high scores
(-b) and alignments (-d) that are displayed.  Previously, fasta33 -E
10.0 -d 10 would show 50 best scores, rather than all the scores with
E() < 10.0.  To get the -E threshold to limit, -E 10.0 -b 10000 -d 10
was required. This is now fixed. Setting "-d 10" does not affect the
number of best scores shown.

Minor change in mw.h to remove unused defines.

fasta3x.me (fasta3x.doc) updated.

>>January 6, 2000
  --> v33t03

Corrected bug in memory mapped reads of gcg_binary format files
that potentially caused the last 63 residues to be read improperly.

Changes to comp_thr.c, pthr_subs.c, uthr_subs.c, ibm_pthr_subs.c to
ensure that each thread has its own work_info structure. This solves
some minor race conditions that sometimes caused some parameters
not to be reported properly.

Changes to most of the drop*.c files to correct some minor problems
with sequence alphabets. Code in mmgetaa.c (memory mapped code for
FASTA, GCG compressed files) reordered to prevent files from being
memory mapped if appropriate index files are not available.

See readme.pvm_3.3 for updates to the pvm programs.

>>December 10, 1999
  (no version change - modifications largely affect ps3comp*)

Modifications to showsum.c to deal with 2 scores/sequence.  Modifications
to mmgetaa.c for superfamily numbers.

>>December 7, 1999
 (no version change, previous version not released)

Corrected problem in mmgetaa.c that caused searches on a memory mapped
single long sequence (e.g. Chr22) to fail.  Corrected bug in map_db.c
that caused it to crash on some architectures if a filename was not
specified.  Corrected off-by-three error in fasty/tfasty.  Corrected
indexing error in dropfz2.c.

>>December 5, 1999
 --> v33t02

corrected some bugs in inifa.c/initsw.c/doinit.c that caused
abbreviated function names to be lost.

modify showbest.c, showalign.c to include information on position in
library sequence (bbp->cont) to distinguish subsegment of very long
sequences.  Currently, the new label is available only with -m 6.

>>November 29, 1999
 [t]fastz33 uses v33t02 of fasty function.

Replace dropfz.c with dropfz2.c.  Dropfz2.c interprets any codons,
that include the nucleotide 'N' as the amino 'X'. Previously, 'N' was
treated as 'A', so 'NNN' ended up 'K'.  This modification, together
with the -S option and lower-case pseg'ed databases, should ensure
that DNA queries with large numbers of 'N's do not match low
complexity regions.

>>November 20, 1999
 (no version change, previous version not released)

Modify initfa.c to disply initn, init1 scores for [t]fast[fs].
Include "-B" option to show previous z-scores.

>>November 17, 1999
 (no version change, previous version not released)

Modify dropfx.c to use saatran(), rather than aatran().  saatran
translates any 'N' containing codon as 'X'.  aatran() treats 'N' as
an 'A'.  Although more steps are required for translation, the program
appears to run just as fast.

>>November 7, 1999
 --> v33t01

Substantial changes to the output format in showbest.c (the list of
high scoring sequences) and showalign.c (the alignments).  The classic
list of best scores:

The best scores are:                             initn init1 opt z-sc E(82014)
gi|121716|sp|P10649|GTM1_MOUSE GLUTATHIO  ( 218) 1497 1497 1497 1761.1 2.3e-91
gi|121717|sp|P04905|GTM1_RAT GLUTATHIONE  ( 218) 1413 1413 1413 1662.9 6.7e-86

has been replaced by:

The best scores are:                                       opt bits E(82138)
gi|121716|sp|P10649|GTM1_MOUSE GLUTATHIONE S-TRAN  ( 218) 1497 354 7.6e-98
gi|121717|sp|P04905|GTM1_RAT GLUTATHIONE S-TRANSF  ( 218) 1413 335 5.3e-92

This display provides more information and removes the outdated initn
and init1 scores, which are no longer used. The "bit" score is
comparable to the blast2 bit score.  It is calculated as: (lambda*S -
ln K)/ln 2, where S is the raw similarity score, lambda and K are
statistical parameters estimated from the distribution of unrelated
sequence similarity scores.  All of the similarity scores, including
init1, initn, and z-scores are reported with the alignment data.
Z-scores are displayed instead of bit scores in the list of high
scores if the command line option "-B" is specified.

In addition, the alignment score line has changed from:

>>gi|2506495|sp|P20136|GTM2_CHICK GLUTATHIONE S-TRANSFER  (220 aa)
 initn: 954 init1: 954 opt: 958 Z-score: 1130.9 expect() 1.1e-56
Smith-Waterman score: 958;  61.927% identity in 218 aa overlap (1-218:1-218)

to:

>>gi|2506495|sp|P20136|GTM2_CHICK GLUTATHIONE S-TRANSFER  (220 aa)
 initn: 954 init1: 954 opt: 958  Z-score: 1130.9  bits: 216.4 E(): 2.8e-56
Smith-Waterman score: 958;  61.927% identity in 218 aa overlap (1-218:1-218)

In addition to the addition of the "bits:" score, the "expect()" label
has changed to "E()" to save some space.

>>November 4,12, 1999
(no version change)

Fixed serious bug in -z 2 lambda/K calculation in scaleswn.c

Fixed bugs in llgetaa.c (openlib()) and definition of superfamily
numbers.

>>October 21, 1999
(no version change)

Begin using CVS for version control. Correct faulty error message in
dropfs.c.  Corrected bad "goto loopl;" in dropfz.c.  Corrected prss3.rsp
for Makefile.tc (Win32 version).

>>October 18, 1999
 --> v33t0

Corrected some serious bugs with the various fasta/x/y programs when
the -DALLOCN0 was used to save memory.  Improvements to fasta3x.me/.doc
documentation.

>>October 12, 1999
 --> v33tx

For this initial release of version 33 of the FASTA programs, the
Makefile's have been modified to make "fasta33(_t)", "fastx33(_t)",
etc, so that you can test fasta33 while retaining fasta3 (from release
v32t08).  The FASTA33 programs are somewhat slower than previous
releases, but I believe the ability to handle low complexity regions
without 'X'ing them out outweighs the slowdown.  By (temporarily)
changing the names of the programs slightly, it will be easier for you
to judge the relative cost and benefit.  To "make" the programs as
"fasta3(_t)", etc, simply replace "Makefile33.common" with
"Makefile.common" in the "Makefile" that you use.

>>September 30, 1999

ssearch3/fasta3/fastx3/fasty3 have been modified to search databases
containing both upper and lower case letters, where lower case letters
indicate low-complexity regions.  With the modified programs, lower
case letters are treated as 'X's' in the initial scan, but are then
treated normally in the final alignment.  In addition, alignments can
contain lower case letters.  Lower case letters are treated as
low-complexity regions during the seach phase of the program, but as
"conventional" residues during the alignment phase, with the "-S"
option.  Currently, lower case letters are mapped to 'X's during the
scan of the entire library.  In the future, alternate weights will be
available. This is a substantial improvement for very large scale
comparison, where one seeks both accurate statistical estimates and
accurate %identities and alignments, and for translated DNA:protein
comparisons, like "fastx3" and "fasty3", where out-of-frame
translations tend to match low complexity regions (see Pearson et
al. (1997) Genomics 46:24-36).

Protein databases (and query sequences) can be generated in the
appropriate format using John Wooton's "pseg" program, available from
ftp://ftp.ncbi.nih.gov/pub/seg/pseg.  Once you have compiled the "pseg"
program, use the command:

	pseg database.fasta -z 1 -q  > database.lc_seg

Once you have database.lc_seg, run the command "map_db" to generate
a ".xin" file that can be used to efficiently memory map the database.

You can then search database.lc_seg with or without the "-S" option.
Without "-S", the database is treated as any other FASTA format file -
all the residues are present.  With "-S", lower case residues will be
treated as 'x's' during the initial scan but as normal residues when
final alignments are displayed.

When the -S option is used, the matrix information line is changed
from: "BL50 matrix (15:-5)" to "BL50 matrix (15:-5)xS".  The "-S"
option is no longer available to provide a scoring matrix offset.

Unfortunately, Blast2.0 format files cannot contain lower case
letters.  We have addressed this problem by providing efficient memory
mapped access to Fasta and GCG/PIR, and GCG/compressed-binary files in
the last release of fasta32t08. The memory mapped file I/O
improvements are provided in fasta33 as well.

================ readme.v32 ================

FASTX/Y and FASTA (DNA) are now half as fast, because the programs now
search both the forward and reverse strands by default.

The documentation in fasta3x.me/fasta3x.doc has been substantially
revised.

>>October 20, 1999
(no version change)

Modify nxgetaa.c/nmgetaa.c to recognize 'N' as a possible DNA character.

>>October 9, 1999
 --> v32t08 (no version number change)

Added "-M low-high" option, where low and high are inclusion limits
for library sequences.  If a library sequence is shorter than "low" or
longer than "high", it will not be considered in the search.  Thus,
"-M 200-250" limits the database search to proteins between 200 and
250 residues in length.  This should be particularly useful for fasts3
and fastf3.  -M -500 searches library sequences < 500; -M 200 -
searches sequences > 200.  This limit applies only to protein
sequences.

Modified scaleswn.c to fall back to maximum likelihood estimates of
lambda, K rather than mean/variance estimates. (This allows MLE
estimation to be used instead of proc_hist_n when a limited range of
scores is examined.)

>>October 2, 1999
 --> v32t08

Many changes:

(1) memory mapped (mmap()ed) database reading - other database reading fixes
(2) BLAST2 databases supported
(3) true maximum likelihood estimates for Lambda, K
(4) Misc. minor fixes

(1) (Sept. 26 - Oct. 2, 1999) Memory mapped database access.
It is now possible to use mmap()ed access to FASTA format databases,
if the "map_db" program has been used to produce an ".xin" file.  If
USE_MMAP is defined at compile time and a ".xin" file is present, the
".xin" will be used to access sequences directly after the file is
mmap()ed.  On my 4-processor Alpha, this can reduce elapsed time by
50%. It is not quite as efficient as BLAST2 format, but it is close.

Currently, memory mapping is supported for type 0 (FASTA), 5
(PIR/GCG ascii), and 6 (GCG binary).  Memory mapping is used if a
".xin" file is present. ".xin" files are created by the new program
"map_db".  The syntax for "map_db" is:

	map_db [-n] "/dir/database.fa"

which creates the file /dir/database.fa.xin.  Library types can be
included in the filename; thus:

	map_db -n "/gcggenbank/gb_om.seq 6"

would be used for a type 6 GCG binary file.

The ".xin" file must be updated each time the database file changes.
map_db writes the size of the database file into the ".xin" file, so
that if the database file changes, making the ".xin" offset
information invalid, the ".xin" file is not used. "list_db" is
provided to print out the offset information in the ".xin" file.

(Oct 2, 1999) The memory mapping routines have been changed to
allow several files to be memory mapped simultaneously. Indeed, once a
database has been memory mapped, it will not be unmap()ed until the
program finishes.  This fixes a problem under Digital Unix, and should
make re-access to mmap()ed files (as when displaying high scores and
alignments) much more efficient.  If no more memory is available for
mmap()ing, the file will be read using conventional fread/fgets.

(Oct 2, 1999) The names of the database reading functions has been
changed to allow both Blast1.4 and Blast2.0 databases to be read.  In
addition, Makefile.common now includes an option to link both
ncbl_lib.o and ncbl2_lib.o, which provides support for both libraries.
However, Blast1.4 support has not been tested.

The Makefile structure has been improved.  Each architecture specific
Makefile (Makefile.alpha, Makefile.linux, etc) now includes
Makefile.common.  Thus, changes to the program structure should be
correct for all platforms.  "map_db" and "list_db" are not made with
"make all".

The database reading functions in nxgetaa.c can now return a database
length of 0, which indicates that no residues were read.  Previously,
0-length sequences returned a length of 1, which were ignored.
Complib.c and comp_thr.c have changed to accommodate this
modification.  This change was made to ensure that each residue,
including the last, of each sequence is read.

Corrected bug in nxgetaa.c with FASTA format files with very long
(>512 char) definition lines.

(2) (September 20, 1999) BLAST2 format databases supported

This release supports NCBI Blast2.0 format databases, using either
conventional file reading or memory mapped files.  The Blast2.0 format
can be read very efficiently, so there is only a modest improvement in
performance with memory mapping.  The decision to use mmap()'ed files
is made at compile time, by defining USE_MMAP.  My thanks to Eamonn
O'Toole of DEC/Compaq, and Daryl Madura of Sun Microsystems, for
providing mmap()'ed modifications to fasta3.  On my machines, Blast2.0
format reduces search time by about 30%.  At the moment, ambiguous DNA
sequences are not decoded properly.

(3) (September 30, 1999) A new statistical estimation option is
available.  -z 2 has been changed from ln()-scaling, which never
should have been used, to scaling using Maximum Likelihood Estimates
(MLEs) of Lambda and K.  The MLE estimation routines were written by
Aaron Mackey, based on a discussion of MLE estimates of Lambda and K
written by Sean Eddy.  The MLE estimation examines the middle 95% of
scores, if there are fewer than 10000 sequences in the database;
otherwise it excludes (censors) the top 250 scores and the bottom 250
scores.  This approach seems to effectively prevent related sequences
from contaminating the estimation process.  As with -z 1, -z 12 causes
the program to generate a shuffled sequence score for each of the
library sequences; in this case, no censoring is done.  If the
estimation process is reliable, Lambda and K should not vary much with
different queries or query lengths.  Lambda appears not to vary much
with the comparison algorithm, although K does.

(4) Minor changes include fixes to some of the alignment display routines,
individual copies of the pstruct structure for each thread, and some
changes to ensure that every last residue in a library is available
for matching (sometime the last residue could be ignored).  This
version has undergone extensive testing with high-throughput sequences
to confirm that long sequences are read properly.  Problems with
fastf3/fasts3 alignment display have also been addressed.

>>August 26, 1999 (no version change - not released)

Corrected problem in "apam.c" that prevented scoring matrices from
being imported for [t]fasts3/[t]fastf3.

>>August 17, 1999
 --> v32t07

Corrected problem with opt_cut initialization that only appeared
with pvcomp* programs.

Improved calculation of FASTA optcut threshold for DNA sequence
comparison for match scores much less than +5 (e.g. +3).  The previous
optcut theshold was too high when the match penalty was < 4 and
ktup=6; it is now scaled more appropriately.

Optcut thresholds have also been raised slightly for
fastx/y3/tfastx/y3.  This should improve performance with minimal
effects on sensitivity.

>>July 29, 1999
(no version change - date change)

Corrected various uninitialized variables and buffer overruns
detected.

>>July 26, 1999 - new distribution
(no version change - v32t06, previous version not released)

Changed the location of "(reverse complement)" label in tfasta/x/y/s/f
programs.

Statistical calculations for tfasta/x/y in unthreaded version
corrected.  Statistical estimates for threaded and unthreaded versions
of the tfasta/x/y/s/f programs should be much more consistent.

Substantial modifications in alignment coordinate calculation/
presentation.  Minor error in fastx/y/tfastx/y end of alignment
corrected.  Major problems with tfasta alignment coordinates
corrected.  tfasta and tfastx/y coordinates should now be consistent.

Corrected problem with -N 5000 in tfasta/x/y3(_t) searches encountered
with long query sequences.

Updated pthr_subs.c/Makefile.linux to increase the pthreads stacksize
to try to avoid "cannot allocate diagonal arrays" error message.
Pthreads stacksize can be changed with RedHat 6.0, but not RedHat 5.2,
so Makefile.linux uses -DLINUX5 for RedHat5.* (no pthreads stack size).
I am still getting this message, so it has not been completely
successful.  Makefile.linux now uses -DALLOCN0 to avoid this problem,
at some cost in speed.

The pvcomp* programs have been updated to work properly with
forward/reverse DNA searches.  See readme.pvm_3.2.

>>July 7, 1999 - not released
 --> v32t06

Corrected bug in complib.c (fasta3, fastx3, etc) that caused core
dumps with "-o" option.

Corrected a subtle bug in fastx/y/tfastx/y alignment display.

>>June 30, 1999 - new distribution
(no version change)

Corrected doinit.c to allow DNA substitution matrices with -s matrix
option.

Changed ".gbl" files to ".h" files.

>>June 2 - 9, 1999 - new distribution
(no version change)

Added additional DNA lambda/K/H to alt_param.h.  Corrected some
other problems with those table. for the case where (inf,inf)
gap penalties were not included.

Fixed complib.c/comp_thr.c error message to properly report filename
when library file is not found.

Included approximate Lambda/K/H for BL80 in alt_parms.h.
BL80 scoring matrix changed from 1/3 bit to 1/2 bit units.

Included some additional perl files for searchfa.cgi, searchnn.cgi
in the distribution (my-cgi.pl, cgi-lib.pl).

>>May 30, 1999, June 2, 1999 - new distribution
(no version number change)

Added Makefile.NetBSD, if !defined(__NetBSD__) for values.h.  Changed
zs_to_E() and z_to_E() in scaleswn.c to correctly calculate E() value
when only one sequence is compared and -z 3 is used.

>>May 27, 1999
(no version number change)

Corrected bug in alignment numbering on the % identity line
	27.4% identity in 234 aa (101-234:110-243)
for reverse complements with offset coordinates (test.aa:101-250)

>>May 23, 1999
(no version number change)

Correction to Makefile.linux (tgetaa.o : failed to -DTFAST).

>>May 19, 1999
(no version number change)

Minor changes to pvm_showalign.c to allow #define FIRSTNODE 1.
Changes to showsum.c to change off-end reporting.  (Neither of these
changes is likely to affect anyone outside my research group.)

>>May 12, 1999
 --> v32t05

Fixed a serious bug in the fastx3/tfastx3 alignment display which
caused t/fastx3 to produce incorrect alignments (and incorrectly low
percent identities).  The scores were correct, but the alignment
percent identities were too low and the alignments were wrong.

Numbering errors were also corrected in fastx3/tfastx3 and
fasty3/tfasty3 and when partial query sequences were used.

>>May 7, 1999

Fixed a subtle bug in dropgsw.c that caused do_work() to calculate
incorrect Smith-Waterman scores after do_walign() had been called.
This affected only pvcompsw searches with the "-m 9" option.

>>May 5, 1999

Modified showalign.c to provide improved alignment information that
includes explicitly the boundaries of the alignment.  Default
alignments now say:

Smith-Waterman score: 175;  24.645% identity in 211 aa overlap (5:207-7:207)

>>May 3, 1999

Modified nxgetaa.c, showsum.c, showbest.c, manshowun.c to allow a
"not" superfamily annotation for the query sequence only.  The
goal is to be able to specify that certain superfamily numbers be
ignored in some of the search summaries.  Thus, a description line
of the form:

>GT8.7 | 40001 ! 90043 | transl. of pa875.con, 19 to 675

says that GT8.7 belongs to superfamily 40001, but any library
sequences with superfamily number 90043 should be ignored in any
listing or summary of best scores.

In addition, it is now possible to make a fasta3r/prcompfa, which is
the converse of fasta3u/pucompfa. fasta3u reports the highest scoring
unrelated sequences in a search using the superfamily annotation.
fasta3r shows only the scores of related sequences.  This might be
used in combination with the -F e_val option to show the scores
obtained by the most distantly related members of a family.

>>April 25, 1999

 -->v32t04 (not distributed)

Modified nxgetaa.c to remove the dependence of tgetaa.o on TFASTA
(necessary for a more rational Makefile structure).  No code changes.

>>April 19, 1999

Fixed a bug in showalign.c that displayed incorrect alignment coordinates.
(no version number change).

>>April 17, 1999

 --> v32t03

A serious bug in DNA alignments when the sequence has been broken into
multiple segments that was introduced in version fasta32 has been
fixed.  In addition, several minor problems with -z 3 statistics on
DNA sequences were fixed.

Added -m 9 option, which unfortunately does different things in
pvcompfa/sw and fasta3/ssearch3.  In both programs, -m 9 provides the
id's of the two sequences, length, E(), %_ident, and start and end of
the alignment in both sequences.  pvcompfa/sw provides this
information with the list of high scoring sequences.  fasta3/ssearch3
provides the information in lieu of an alignment.

>>March 18, 1999

 --> v32t02

Added information on the algorithm/parameter description line to
report the range of the pam matrices.  Useful for matrices like
MD_10, _20, and _40 which require much higher gap penalties.

>>March 13, 1999 (not distributed)

 --> v32t01

 -r results.file  has been changed to -R results.file to accomodate
 DNA match/mismatch penalties of the form: -r "+1/-3".

>>February 10, 1999

Modify functions in scalesw*.c to prevent underflow after exp() on
Alpha Linux machines.  The Alpha/LINUX gcc compiler is buggy and
doesn't behave properly with "denormalized" numbers, so "gcc -g -m
ieee" is recommended.

Add "Display alignments also (y/n)[n] "

pvcomplib.c again provides alignments!!  In addition, there is a
new "-m 9" option, which reports alignments as:

>>>/home/wrp/slib/hlibs/hum0.aa#5>HS5 gi:1280326 T-cell receptor beta chain 30 aa, 30 aa vs /home/wrp/slib/hlibs/hum0.seg library
HS5         	  30	HS5         	  30	1.873e-11	1.000	  30	   1	  30	   1	  30
HS5         	  30	HS2249      	  40	1.061e-07	0.774	  31	   1	  30	   7	  37
HS5         	  30	HS2221      	  38	1.207e-07	0.833	  30	   1	  30	   7	  35
HS5         	  30	HS2283      	  40	1.455e-07	0.774	  31	   1	  30	   7	  37
HS5         	  30	HS2239      	  38	1.939e-07	0.800	  30	   1	  30	   7	  35

where the columns are:

query-name      q-len   lib-name      lib-len   E()             %id    align-len  q-start q-end   l-start l-end

>>February 9, 1999

Corrected bug in showalign.c that offset reverse complement alignments
by one.

>>Febrary 2, 1999

Changed the formatting slightly in showbest.c to have columns line up better.

>>January 11, 1999

Corrected some bugs introduced into fastf3(_t) in the previous version.

>>December 28, 1998

Corrected various problems in dropfz.c affecting alignment scores
and coordinates.

Introduced a new program, fasts3(_t), for searching with peptide
sequences.

>>November 11, 1998

  --> v32t0

Added code to correct problems with coordinate number in long library
sequences with tfastx/tfasty.  With this release, sequences should be
numbered properly, and sequence numbers count down with reverse
complement library sequences.

In addition, with this release, fastx/y and tfastx/y translated
protein alignments are numbered as nucleotides (increasing by 3,
labels every 30 nucleotides) rather than codons.

  $Id: readme.v34t0 348 2010-07-20 21:33:22Z wrp $
  $Revision: $

>>May 28, 2007

Small modification for GCG ASCII (libtype=5) header line.

>>January 12, 2007	fasta-34_26_2

Fix a problem with pssm_asn_subs.c reading strings (sequences) longer
than 1024 bytes.

Remove searchfa.cgi, searchnn.cgi, cgi-lib.pl, my-cgi.pl - this code
was used for an ancient FASTA WWW implementation and has been replaced
by the FASTA_WWW package.

FASTA Version numbers are being modified to make releases easier to
track, thus fa34t26b5 has become fasta-34_26_1.  I would prefer to use
decimal versions, but CVS does not allow '.' in tags.

>>January 4, 2007	fasta-34_26_1

Include scripts for building Mac OS X Universal binaries on a PPC
machine.  Programs are compiled first with Makefile.os_x (gcc-3.3 for
PPC) and then installed into ./ppc/.  Programs are next compiled with
Makefile.os_x86 for i386, and the resulting executables installed into
./i386/.  Finally, the "make_osx_univ.sh" script is run to build the
universal binaries from the two executables using "lipo".

>>December 12, 2006

Fix some problems with p2_workcomp.c: (1) no longer initialize pad
characters for non-existant sequences. (2) deal with small libraries
consistently with the serial versions.

>>November 17, 2006	fa34t26b5

Fixed a problem reading ASN.1 format 2 PSSM's.  It is now possible to
download a PSI-BLAST PSSM RID and search properly.  Next, the query
sequence from the PSSM should be used instead of the provided query
sequence, so that the query sequence is ignored.

>>October 19, 2006	fa34t26b4

Fixed problem with SSE2 code when PSSM's are used.

>>October 6, 2006	fa34t26b3

A new set of WIN32 programs is now available that use the Intel C++
9.1 compiler, rather than the much older Borland Turbo-C compiler. All
of the unthreaded programs that are part of the Unix and MacOSX FASTA
distributions are now available.  Threaded (multiprocessor) versions
of the program as available as well, as are sse2 accelerated versions
of ssearch34 (ssearch34sse2.exe, ssearch34sse2_t.exe).

Th new WIN32 code also uses Microsoft's "nmake" program to build the
programs, which allows much greater consistency between the Unix and
Windows versions.


>>September 18, 2006

Static global alignment variables removed from dropnfa.c, dropfx.c,
dropfz2.c.  dropnfa.c, dropfx.c and dropfz2.c should be thread safe.
Together with the earlier changes, all the FASTA functions should now
be thread safe during the alignment process.

>>August 17, 2006

Begin removal of static variables from Smith-Waterman alignment
functions.  These variables kept the functions from being thread-safe.
Now dropgsw.c and dropnsw.c are thread-safe.

>>August 15, 2006	fa34t26b2

Fixed a problem with pv34compfx/mp34compfx (and fy) producing
improperly labeled alignments and de-allocating memory for the reverse
complement.

>>July 18, 2006

The library file name parsing programs now provide the option for
environment variable substitions.  For example, SLIB2=/slib2 as an
environment variable (e.g. export SLIB2=/slib2 for ksh and bash), then

	fasta34 -q query.aa '${SLIB2}/swissprot.fa'  expands as expected.

While this is not important for command lines, where the Unix shell
would expand things anyway, it is very helpful for various
configuration files, such as files of file names, where:

	<${SLIB2}/blast
	swissprot.fa

now expands properly, and in FASTLIBS files the line:

	NCBI/Blast Swissprot$0S${SLIB2}/blast/swissprot.fa

expands properly.  Currently, Environment variable expansion only
takes place for library file names, and the <directory in a file of
file names.

>>July 14, 2006	  fa34t26b1

Updated Farrar smith_waterman_sse2.c code to address possible bug
(code from Michael Farrar).  Include <sunmedia_intrin.h> for
compilation with Sun compiler with Makefile.sun_x86.

>>July 2, 2006	  fa34t26b0

This release provides an extremely efficient SSE2 implementation of
the Smith-Waterman algorithm for the SSE2 vector instructions written
by Michael Farrar (farrar.michael@gmail.com).  The SSE code speeds up
Smith-Waterman 8 - 10-fold in my tests, making it comparable to Eric
Lindahl's Altivec code for the Apple/IBM G4/G5 architecture.

The Farrar code is largely confined to smith_waterman_sse2.c and
smith_waterman_sse2.h, which are copyright (2006) by Michael Farrar,
and cannot be redistributed without his permission.  Mr. Farrar has
agreed to provide his code under the same policy used by FASTA -
e.g. the code can be used without permission, but not redistributed.

The Farrar code uses GCC version 4.0 SSE2 intrinsic functions to avoid
assembly language code.  Unfortunately, in my hands, "gcc -O3" causes
"out of memory" errors, and other problems, so "gcc -O" is used instead.

>>June 23, 2006   fa34t25d10

Modifications to comp_lib.c, compacc.c, and other files to ensure that
function-specific MAXTOT values are used properly.  MAXTOT is now
available as m_msg.max_tot, which is set in initfa.c (m_msg.max_tot =
MAXTOT) to ensure that functions that need very large MAXTOT values
(e.g. TFASTX) can get them.  tfastx can now search successfully with
titin, a 27,000 residue protein.

Other changes have been made to accomodate long query sequences.

A serious bug was found in fastx34(_t) that caused alignment
coordinates to be calculated improperly when the DNA sequence was much
longer than the protein sequence.

>>May 31, 2006	fa34t25d9

Fixed some problems with fasts/fastf alignments when -m 9 options were
used.  Unlike the other algorithms, the a_res structure does not
capture all the information to re-produce an alignment, so do_walign
now sets bptr->have_ares to indicate whether the a_res structure is
valid.

Various problems with bad library names, and short query titles were
also fixed.

Updated version number/date on all drop*.c functions.

>>May 24, 2006	fa34t25d8

Revised code for NCBI *.pal/*.nal databases has been tested on all
architectures, including Windows.

In addition, support for ASN.1 PSSM:2 files provided by the NCBI
PSI-BLAST WWW site is included.  This code will not work with
iteration 0 PSSM's (which have no PSSM information).  For ASN.1
PSSM's, which provide the matrix name (and in some cases the gap
penalties), the scoring matrix and gap penalties are set appropriately
if they were not specified on the command line. ASN.1 PSSM's are type 2:
	ssearch34 -P "pssm.asn1 2" .....

>>May 18, 2006

Support for NCBI Blast formatdb databases has been expanded.  The
FASTA programs can now read some NCBI *.pal and *.nal files, which are
used to specify subsets of databases.  Specifically, the
swissprot.00.pal and pdbaa.00.pal files are supported.  FASTA supports
files that refer to *.msk files (i.e. swissprot.00.pal refers to
swissprot.00.msk); it does not currently support .pal files that
simply list other .pal or database files (e.g. FASTA does not support
nr.pal or swissprot.pal).

In the process of providing this support, the routines used to read
ASN.1 binary formatdb files were substantially improved.  It is now
possible to see multiple description lines for a single sequence.

IS_BIG_ENDIAN has been removed from all of the Makefiles.  The code
now looks for the definition of __BIG_ENDIAN__ or _BIG_ENDIAN to
decide whether the architecture IS_BIG_ENDIAN.  If, for some reason,
one of these macros is not defined on a BIG_ENDIAN architecture, then
-DIS_BIG_ENDIAN is required.

>>May 12, 2006	CVS fa34t25d7

Corrected serious problem with coordinate display calculation for
fasta34 and ssearch34 - in some cases the coordinates and alignment
symbols were off by the length of the context (typically 30 residues).

Added capability to read ASN.1 binary PSSM information.  This
information is provided (in an encoded form) from the NCBI PSI-BLAST
WWW site.  (What is actually provided from the WWW site is a bzip2-ed
binary file that is converted to ASCII HEX.  The ASCII HEX file must
be converted to binary, and then bunzip'ed. This bunzip-ed file is
binary ASN.1.)  These files can also be generated by

 blastpgp -J T -C pssm.asn1_bin -u 2

I am parsing the ASN.1 binary manually, not using the NCBI toolkit, so
there may be some files that are not parsed properly - if so, let me
know.

(May 12, 2006 - The NCBI changed the format of the psi-blast ASN.1
PSSM - and has not yet provided documentation of the new structure, so
this code does not work. It does work with blastpgp v 2.2.13, but not
with the web site version 2.2.14.  A fix was provided 24-May-2006)

>>April 18, 2006

Small modification in mshowbest.c to provide more consistent display
widths with -m 9i in list of best hits.

>>April 11, 2006 CVS fa34t25d6

Corrected a problem introduced with the new, more efficient method for
displaying alignments.  For the tfast* programs, which must translate
the library sequence, translations were not done when alignments were
re-displayed.

Corrected an older problem with tfastx34 against very long sequence
databases - the code to more efficiently do the display alignment did
not use the correct sequence coordinates.

Modifications to dropfs2.c to ensure that exact peptide matches are
captured more frequently.

>>March 16, 2006 CVS fa34t25d5

Change to initfa.c to allow lower case DNA libraries using the
-DDNALIB_LC compile time option.

Modify p2_complib.c, p2_worklib.c (and doinit.c, msg.h) to allow the
-V annotation option for the parallel programs.  Also modify to allow
specification of the query range (but only for the first query, like
fasta34) for the parallel programs.

Modification of p2_workcomp.c to correct some problems presenting
percent similarity.  Also correct unreleased bugs in the alignment
routines that allow more efficient alignment re-calculation.

>>Nov 20, 2005

Changes to support asymmetric matrices - a scoring matrix read in from
a file can be asymmetric.  Default matrices are all symmetric.

>>Oct 24, 2005

Modifications extended to p2_complib.c/p2_workcomp.c.  Incorporation
of drop_func.h into p2_workcomp.c greatly simplifies things.  No
changes in communication - struct a_res_str is internal to
p2_workcomp.c.

Additional changes to do_walign() so that aln_func_vals() must be
called to set llfact, qlfact, etc in a_struct aln before or after
do_walign is called.  do_walign produces a_res_str a_res, which has
all the information necessary to produce a calcons() or calc_code()
alignment.

>>Oct 19, 2005 CVS fa34t26b0

Modifications to drop*.c and c_dispn.c to separate (and simplify) some
of the alignment coordinate calculations.  Before, the "a_struct" had
the coordinates of the alignment used in the display (seqc0, seqc1)
AND in the original sequences (aa0, aa1), as well as other information
used to calculate alignment coordinates.  In the new version, astruct
coordinates always refer to seqc0,1, while a new structure, a_res_str,
has coordinates for aa0, aa1 as well as the alignment encoding in res[nres].
Eventually, this should make it possible to display multiple local
alignments from the same two sequences.

In addition, the file "drop_func.h" has been added to the project, and
is included by many of the files (all the drop*.c functions,
mshowbest.c, mshowalign.c) to ensure that the various functions are
declared and used consistently.

>>Sept 19, 2005	CVS fa34t25d4

Changes to support Mac OS 10.4 - Tiger (include sys/types.h in more
files).  Documentation update for prss34/prfx34. Modifications to
comp_lib.c to support prss34_t/prfx34_t.  Shuffle numbers for
prss/prfx can now be specified by "-k #".

>>Sept 2, 2005

The prss34 program has been modified to use the same display routines
as the other search programs.  To be more consistent with the other
programs, the old "-w shuffle-window-size" is now "-v window-size".

prss34/prfx34 will also show the optimal alignment for which the
significance is calculated by using the "-A" option.

Since the new program reports results exactly like other
fasta/ssearch/fastxy34 programs, parsing for statistical significance
is considerably different.  The old format program can be make using
"make prss34o".

>>Aug 26, 2005

Modifications to save_best() in comp_lib.c to support prss34_t.  It
did not work before.

>>July 25, 2005

Modify mshowbest.c to suppress gi|12345 in HTML mode.

>>July 18, 2005	CVS fa34t25d3

Modifications to Makefile.tc to support NCBI formatdb formats under
Windows.

>>May 19, 2005  CVS fa34t25d2

Modifications to dropfs2.c to fix an obscure bug that occurred when
correctly ordered peptides aligned one residue apart.

>>May 5, 2005 CVS fa34t25d1

Modification to the -x option, so that both an "X:X" match score and
an "X:not-X" mismatch score can be specified. (This score is also used

give a positive score to a "*:*" match - the end of a reading frame,
while giving a negative score to "*:not-*".

>>March 14, 2005  CVS fa34t25b4

Fixed some problems caused by padding characters required for
Smith-Waterman ALTIVEC in the parallel (p2_complib.c, p2_workcomp.c)
versions.

>>Feb 24, 2005	CVS fa34t25b3

Changes to comp_lib.c (and Makefile.pcom) to support prss34_t.

>>Feb 12, 2005

Modify dropfs.c to dynamically allocate space for alignments, so that
queries with a large number of fragments can still place all the
fragments on the alignment.  Also fix a problem produced by removing
-DBIGMEM from most of the Makefile's, but not fixing defs.h to use
BIGMEM sizes by default.

>>Jan 24, 2005

Include a new program, "print_pssm", which reads a blastpgp binary
checkpoint file and writes out the frequency values as text.  These
values can be used with a new option with ssearch34(_t) and prss34,
which provides the ability to read a text PSSM file.  To specify a
text PSSM, use the option -P "query.ckpt 1" where the "1" indicates a
text, rather than a binary checkpoint file.  "initfa.c" has also been
modified to work with PSSM files with zero's in the in the frequency
table.  Presumably these positions (at the ends) do not provide
information. (Jan 26, 2005) blastpgp actually uses BLOSUM62 values
when zero frequencies are provided, so read_pssm() has been modified
to use scoring matrix values for zero frequencies as well.

>>Jan 13, 2005

Change to initfa.c to have fasts34 do a protein comparison by default,
rather than an unknown sequence type.  Automatic checking for fasts34
does not work reliably, because queries can be very short.  Likewise
for fastm34.  [Jan 26, 2004] Undo this change, which broke DNA
comparison when "-n" was specified.

>>Jan 7, 2005

Changes to tatstats.h, dropfs2.c to allow larger numbers of peptides
to match when fasts is used to show coverage on a proteomics
experiment.  Previously fasts could match no more than 30 peptides,
that has been increased to 50.  In addition, ktup=2 can be used
to increase the likelihood that short exact matchs trump longer
mismatched regions.

>>Nov 11, 2004	   CVS fa34t25

Finished merge of earlier fa34t24 branch with HEAD.  Correct
labeling of TFASTM.

>>Nov 4-8, 2004

Incorporation of Erik Lindahl "anti-diagonal" Altivec code for
Smith-Waterman, only.  Altivec SSEARCH is now faster than FASTA for
query sequences < 250 amino acids.

Small modifications to output score display to ensure that the correct
scores are shown, and that they are correctly labeled.

>>Aug 25,26, 2004  CVS fa34t24b3

Small change in output format for p34comp* programs in
">>>query_file#1 string" line before alignments.  This line is not present
in the non-parallel versions - it would be better for them to be consistent.

Change in last_stats.c to properly label fasts statistics with -z != 1.

Change in dropfs2.c to ensure that tatprobs are not precalculated with -z 4.

Modify -m 9i output option to show in HTML output.

Add "#ifdef NOOVERHANG" to dropfs2.c that causes overlapping
alignments to score a 0, rather than the partial overlap score.
Useful for SAGE alignments, because "fasts" requires global alignments
(except for for overhangs, unless NOOVERHANG is defined).

>>Aug 23, 2004

Fix problem with very long definition lines with formatdb version4
ASN databases.  Fix mshowalign.c to re-enable "-L" option.

>>July 28, 2004

Fix to re-enable -w window shuffle for PRSS.  Modify comp_lib.c
for PRSS to ensure that the unshuffled score and probability
are shown, even for very high probabililty alignments.

>>July 21, 2004

Modifications to support PostgreSQL databases with the same commands
as MySQL databases.  MySQL database libraries are type 16, PostgreSQL
are type 17.  Makefile.linux_sql and Makefile.pvm4_sql support both
database types simultaneously.

>>June 23, 2004 CVS fa34t24b2

Additional fixes to enable -n or -p with fasts34 and
fastm34. Makefile.pcom was fixed for fastm34_t.  A new file,
mgstm1.nts, of DNA fragments from mgstm1.seq, is included for testing
fasts34 and fastm34.

>>May 4, 2004

Fixes to initfa.c to allow DNA:DNA for FASTS, FASTM.  This change
introduced a bug that broke FASTS completely, but was fixed June 18,
2004 (and retagged fa34t24b2).

>>April 23, 2004 CVS fa34t24b1

Fix bug in initfa.c that caused tfasts/tfastf not to examine all six
frames.

>>May 4, 2004

Fixes to initfa.c to allow DNA:DNA for FASTS, FASTM.

>>March 19, 2004 CVS fa34t24b0

Modify all the drop*.c files, plus mshowbest.c and mshowalign.c, to
display percent similarity, rather than percent ungapped.  An
alignment is counted as similar if the score is greater than or equal
to zero (the same criterion used for placing ".". To disable this
change, remove -DSHOWSIM from the appropriate Makefile.*.

>>March 18, 2004 CVS fa34t23b8

Fix bug in initfa.c tables that caused prss to generally compare
proteins.

>>March 15, 2004

Fix bug in calls to revcomp(); make revcomp() guarantee NULL termination.

>>March 2, 2004	CVS fa34t23b7

Fix a very embarrassing and surprising bug that caused insertions
in fasta alignments to appear in the wrong sequence.

>>Feb 7, 2004	CVS fa34t23b6

Change initfa.c to allow "-i" (reverse complement) and "-i -3" with
"fastx34" and "prfx34".  In addition, "prfx34" now examines both query
DNA strands in calculated the shuffled statistical significance.

>>Feb 5, 2004

Reverse assignments for G:U baseparing in initfa.c.

Fix memory allocation error caused by doubling DNA alignment width.

>>Jan 7, 2004	CVS fa34t23b5

Change in do_walign() in dropnfa.c to make final DNA alignments use a
band that is 2X as large as the search band width.

>>Dec 22, 2003	CVS fa34t23b4

Fix typo in p2_complib.c that prevented compilation.  Fix problem
with karlin.c for asymmetrical matrices, such as used with -U.

>>Dec 10, 2003  CVS fa34t23b3

Fix problem in resetp()/initfa.c that disabled banded Smith-Waterman
DNA alignments.

Allow spam() to do extended alignments for DNA if one of the sequences
is < 50 nt.

Cause default ktup to drop for short sequences.  For protein < 50, ktup=1;
for DNA < 20, 50, 100 ktup = 1, 2, 3, respectively.

>>Dec 7, 2003

A new option, "-U" is available for RNA sequence comparison.  "-U"
functions like "-n", indicating that the query is an RNA sequence.  In
addition, to account for "G:U" base pairs, "-U" modifies the scoring
matrices so that a "G:A" match has the same score as "G:G" match,
and "T:C" match has the same score as a "T:T" match. (Corrected
13-July-2010 -- the G:A/T:C scores are score(G:G)-3.) The asymmetric
matrix required changes in dropnfa.c that were similar to the changes
in dropgsw.c required for profiles.  In addition, m_msg.qdnaseq and pst.dnaseq
 can now be SEQT_DNA, SEQT_RNA, SEQT_PROT, SEQT_UNK, or SEQT_OTHER.
m_msg.ldnaseq does not use SEQT_RNA, only SEQT_DNA.  A new member of
struct pstruct: int nt_align, is used to indicate nucleotide
alignments.

>>Nov 19, 2003

Changes to Makefile's to distinguish between tatstats_fs.o and
tatstats_ff.o.

>>Nov 2, 2003

Substantial changes to comp_lib.c, p2_complib.c, mshowbest.c, and
mshowalign.c to support more sophisticated display options.
Previously, one could have only on "-m #" option, even though several
of the options were orthogonal (-m 9c is independent of -m 1 and -m2,
which is independent of -m 6 (HTML)).  The programs now use a bitmask
that allows independent options to be combined.  In particular -m 9c
can be combined with -m 6, which can be very helpful for runs that
need HTML output but can also exploit the encoding provided by -m 9c.

The "-m 9" option now also allows "-m 9i", which shows the standard
best score information, plus percent identity and alignment length.

>>Oct 26, 2003	CVS fa34t23b1

Additional fixes to Makefiles to enable tfastf34(_t).  Changes to
support ossearch34 (a non-Phil Green optimized Smith-Waterman).

>>Oct 8, 2003	CVS fa34t23b0

Fixes to get DNA queries working in both directions, and to fix PCOMPLIB
programs for "-V" option.  Currently, the parallel programs cannot use
the "-V" option.

>>Sept 25, 2003

A new option is available for annotating alignments.  -V '@#?!'
can be used to annotate sites in a sequence, e.g:
	>GTM1_HUMAN ...
	PMILGYWDIRGLAHAIRLLLEYTDS@S?YEEKKYT@MG
	DAPDYDRS@QWLNEKFKLGLDFPNLPYLIDGAHKIT
might mark known and expected (S,T) phosphorylation sites.  These
symbols are then displayed on the query coordinate line:

               10        20    @?  30  @     40  @     50        60
GTM1_H PMILGYWDIRGLAHAIRLLLEYTDSSYEEKKYTMGDAPDYDRSQWLNEKFKLGLDFPNLP
       ::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::
gtm1_h PMILGYWDIRGLAHAIRLLLEYTDSSYEEKKYTMGDAPDYDRSQWLNEKFKLGLDFPNLP
               10        20        30        40        50        60

This annotation is mostly designed to display post-translational
modifications detected by MassSpec with FASTS, but is also available
with FASTA and SSEARCH.

>>Sept 22, 2003	  CVS fa34t22b5

The Altivec Smith-Waterman code has been removed.

>>Sept 17, 2003	  CVS fa34t22b4

A variety of different bugs have been fixed.  (1) All the functions in
the old initsw.c are now in initfa.c; initsw.c will be removed.
Specifically, the Profile/PSSM code is now in initfa.c.  initfa.c is
now fully table driven. (2) various problems with prss34 and prfx34
have been fixed in initfa.c.  (3) An additional ncbl2_mlib.c buffer
overrun has been fixed. (4) fastf34 is now available in this package.
Its performance is very similar to, but not identical to, fastf33.  I
am tracking down the differences.  In general, the raw scores
calculated by both programs are the same, but the statistical analysis
seems to be slightly different.

>>July 30, 2003   CVS fa34t22b3

Fix bug in ncbl2_mlib.c that caused buffer overrun with blast/formatdb
v3 description lines.

>>July 28, 2003

The initfa.c file has been substantially re-structured to use a
table-driven approach to parameter setting, rather than the previous
confusing combinations of #ifdef's.  Two tables of parameters are
used, pgm_def_arr[] and msg_def_arr[], which specify values like the
program name, reference, scoring matrix, default gap penalties, etc.
msg_def_arr[] has the sequence types for the query, library, and
algorithm, as well as other parameters (qframe, nframe, nrelv, etc),
which greatly simplifies the sequence recognition logic.  ppst->pgm_id
can be used to identify the program that is running.  Eventually,
almost all of the program specific #ifdef's will be removed from
initfa.c.  initfa.c now provides initsw.c functionality, so that
initsw.c is no longer needed.

>>July 25, 2003

A new file is included - fasta.defaults - that lists the scoring
matrix, gap penalty, and other defaults for all of the fasta34
programs.  This file will be used soon to simplify parameter setting
for the FASTA programs, and should also be used by Javascript WWW
interfaces to the FASTA programs.

>>July 22, 2003    CVS fa34t22b2

Fixes to dropfs2.c, tatprobs.c to ensure that negative probabilities
cannot occur.  Negative probabilities were never seen with standard
matrices, but did occur with BL50.  Another optimization in dropfs.c
considerably improves fasts34 performance in some cases.

Fix a problem with formatdb v4 ASN.1 format files.

>>July 12, 2003

Fix a bug that prevented "-L" (long sequence descriptions) from
working.

>>July 9, 2003

Fix reverse complement (M:K) error.  Fix off-by-one error for FASTA
DNA alignments that caused the first aligned residue pair to be
missed.

>>July 4 - 8, 2003

Incorporate blast-def-line ASN.1 parsing so that NCBI formatdb version
4 files can be read.

>>June 26, 2003

The strategy for displaying the match/mismatch line (" .:" for -m 0)
has been changed dramatically to acommodate more sophisticated
strategies for indicating conservative replacements, e.g. because of
PSSM's.  In addition to seqc0 and seqc1, which hold the aligned
sequences for display, there is also seqca, which holds the alignment
symbol.  calcons(), do_show(), and discons() have all changed to
include seqca.  calcons() is somewhat more complex; discons() is much
simpler.  (June 29, 2003 - dropgsw.c calcons() now displays profile
similarity accurately - it is very very illuminating.)

>>June 16, 2003	version: fasta34t22

ssearch34 now supports PSI-BLAST PSSM/profiles.  Currently, it only
supports the "checkpoint" file produced by blastall, and only on
certain architectures where byte-reordering is unnecessary.  It has not
been tested extensively with the -S option.

	ssearch34 -P blast.ckpt -f -11 -g -1 -s BL62 query.aa library

Will use the frequency information in the blast.chkpt file to do a
position specific scoring matrix (PSSM) search using the
Smith-Waterman algorithm.  Because ssearch34 calculates scores for
each of the sequences in the database, we anticipate that PSSM
ssearch34 statistics will be more reliable than PSI-Blast statistics.

The Blast checkpoint file is mostly double precision frequency
numbers, which are represented in a machine specific way.  Thus, you
must generate the checkpoint file on the same machine that you run
ssearch34 or prss34 -P query.ckpt.  To generate a checkpoint file,
run:

blastpgp -j 2 -h 1e-6 -i query.fa -d swissprot -C query.ckpt -o /dev/null

(This searches swissprot for 2 iterations ("-j 2" using a E()
threshold 1e-6 saving the resulting position specific frequencies in
query.ckpt.  Note that the original query.fa and query.ckpt must
match.)

>>June 5, 2003

Fix to mshowbest.c to get -m 9 coordinates correct on reverse strand
with pv34comp*.  Some additional fixes for prfx34.

>>May 22, 2003

Changes to llgetaa.c, getseq.c, comp_lib.c to provide a different
library residue lookup table (sascii) for queries and libraries.  This
allows one to make a prfx34 (like prss34, but using the fastx
algorithm).  prfx34 is now available.

>>May 13,14 2003

Fixes to most of the drop*.c files, and mshowbest.c, to ensure that
coordinates displayed with -m 9(c) and the final alignment are
consistent.  They were consistent for fasta34/ssearch34/fasts34, but
not for fastx34/fasty34.  The alignment coordinate system has been
been revised for consistency in allthe drop*.c programs (coordinates
used to be off-by-one for some, but not other functions).

Fixes to -m 9c for fasty34/pv34compfy.  In addition, a problem was
fixed with fastx34/fasty34 that appeared with a protein sequence was
considerably longer than the DNA query, e.g. an EST vs titin (26K
residues).  This problem only appeared on pv34compfx/fy on Xserve's
under OS_X; but it should improve fastx34/fasty34 performance with
very long protein sequences on all platforms.

>>May 7,8 2003

Changes to p2_workcomp.c, compacc.c, and p_mw.h to fix persistent
bugs in the -m 9c display.  Previous pv34comp* programs would not
return the correct coded alignment if more than 100 alignments came
from the same node, or if an encoding was longer than 127 chars.

Also, fixes to p2_complib.c, comp_lib.c, to allow long query sequences
to be segmented.  Previously, only the first 20,000 residues were
used.  The segmented queries are not overlapped; segmented library
sequences are.

>>May 5, 2003

Changes to last_tat.c, scaleswt.c to ensure that all fasts alignments
that are likely to have significant scores are displayed.  In previous
implementations, if the query had more than 10 fragments, only the 100
best scores were shown.  Now, we rescore up to 2500 alignments.  The
new approach allows large mixtures to be used for searches, where some
of the fragments from the mixture match too many proteins
(e.g. actins).  Some differences between the fasts34 and pv34compfs
implementations have been fixed.  The two programs typically will not
give exactly the same results, because of small differences in the
sampling procedures, but the results are essentially equivalent.

>>Apr 11, 2003  CVS fa34t21b3

Fixes for "-E" and "-F" with ssearch34, which was inadvertantly disabled.

A new option, "-t t", is available to specify that all the protein
sequences have implicit termination codons "*" at the end.  Thus, all
protein sequences are one residue longer, and full length matches are
extended one extra residue and get a higher score.  For
fastx34/tfastx34, this helps extend alignments to the very end in
cases where there may be a mismatch at the C-terminal residues.

-m 9c has also been modified to indicate locations of termination
codons ( *1).

>>Mar 17, 2003  CVS fa34t21b2

A new option on scoring matrices "-MS" (e.g. "BL50-MS") can be used to
turn the I/L, K/Q identities on or off.  Thus, to make "fastm34" use
the isobaric identities, use "-s M20-MS".  To turn them off for "fasts34",
use "-s M20".

More fixes for correct alignment coordinates.  There was a conflict between
-m 9 and -m 9c and subsequent alignment displays.

>>Mar 13, 2003

Various fixes to produce correct fastm34 alignments.  Changes to all
functions to correct potential problem with -m 9 alignment coordinates
when both -m 9 and actual alignments are shown.

>>Feb 25,27, 2003

Modifications to re-activate showsum.c, which included corrections to
the showbest() call in p2_complib.c.

>>Feb 13, 2003	CVS fa34t21b1

Modifications to dropfx.c to dramatically improve alignment speed for
cases where the DNA sequence is considerably longer than the protein
sequence.  Previously, a 200 aa vs 5000 nt comparison would do a full
200 x 5000 Smith-Waterman alignment; with this modification, no more
than a 200 x 1200 (2x3x200) alignment is done.  This optimization has
not (yet) been applied to dropfz2.c (fasty/tfasty).

>>Feb 11, 2003

Small modifications to comp_lib.c, p2_complib.c, and nmgetlib.c to
pass openlib() a possibly old lmf_str.  This allows openlib() to
re-use memory mapped files.  closelib() no longer releases memory
mapped file buffers.  Under Linux, memory mapped file buffers were not
really released, so when comparing a set of sequences against nr, the
program could not mmap() the database after several searches.  This
will also speed up memory mapped multiple sequence searches.

>>Jan 28-31, 2003  CVS fa34t21b0

Fix another bug (all of v34t20) involved with overlapping long
sequences.  And another bug that occurred when using sampled
statistics, but appeared only on the SGI platform - thanks to Dmitri
Mikhailov.  Several other issues have been addressed based on more
instrumented runtime testing.

Fix an old (all v34) bug that caused problems with -z 11-16 (shuffled
sequence array was not allocated properly).  Fixed another bug with -z
6/16 when using threaded (_t) searches in fasta34_t.

Restructure statistical analysis functions (scaleswn.c, scaleswt.c) to
return the "final" statistical estimation routine done in pst.zsflag_f.
This allows the program to cope with searches against a single sequence
correctly.

Corrected an error for DNA sequences needing Altschul-Gish statistics.

>>Jan 25, 2003

Add option "-J start:stop" to pv34comp*/mp34comp*.  "-J x" used to
allow one to start at query sequence "x"; now both start and stop can
be specified.

>>Jan 14, 2003

Changes to apam.c to provide an error message on stderr when a scoring
matrix cannot be found.

Changes to dropfs2.c, initsw.c, initfa.c to provide -m9c information
for fasts34 searches.  Modify the alignment algorithm to use
probabilistic scores properly.

>>Dec 22, 2002

Change to compacc.c (sortbeste()) to do a second sort on zscore when
several sequences have E() == 0.

>>Nov 27, 2002

Change FSEEK_T to fseek_t to keep Borland BCC5 happy.

>>Nov 14-22, 2002  CVS fa34t20b6

Include compile-time define (-DPGM_DOC) that causes all the fasta
programs to provide the same command line echo that is provided by the
PVM and MPI parallel programs.  Thus, if you run the program:

    fasta34_t -q -S gtt1_drome.aa /slib/swissprot 12

the first lines of output from FASTA will be:

    # fasta34_t -q gtt1_drome.aa /slib/swissprot
     FASTA searches a protein or DNA sequence data bank
     version 3.4t20 Nov 10, 2002
    Please cite:
     W.R. Pearson & D.J. Lipman PNAS (1988) 85:2444-2448

This has been turned on by default in most FASTA Makefiles.

Fix p2_complib.c so that qstats[] is always allocated before it is used.

Fix serious bug in non-threaded comp_lib.c that caused some high
scoring sequences to be missed by fasts34.  New tests are included in
test.sh to detect this problem in the future.

The shell sort algorithm in sortbeste(), sortbestz(), and sortbesto()
has been modified to use an improved algorithm that will not go
quadratic in pathological cases.

nmgetlib.c and mmgetaa.c have been modified to remove "^A" in libstr
when used with p2_complib.c.

Fix problem with MAXSEG in tatstats.h with IBM/AIX.

Changes to most Makefiles to use -DSAMP_STATS; fixes to p2_complib.c
for SAMP_STATS.

>>Oct 22, Nov 3, Nov 9, 2002   CVS tag fa34t20b5

Fix problem in comp_lib.c that caused the query sequence length to be
counted twice.

Fixed problem with prss34 (updated find_zp in showrss.c).

Correct shuffling function in several places.

Add jitter back to addhistz() - improves appearance with prss34.

Changes to fix problems with aln_code using -m 9c.

Fix to serious bug in scaleswt.c (fasts34, etc) that caused sorts on
the high scores to take much to long.  The program is now 10X faster,
and scales well on PVM/MPI.

Fix to llgetaa.c to work with new getseq() API with automatic alphabet
recognition.

>>Oct 12, 2002 CVS tag fa34t20b4

Several very obscure (and sometimes old) bugs that appeared in certain
MPI environments have been fixed.  This occurred because the pst.sq[]
array did not always have a '\0' at the end.  In addition,
mshowalign.c/p2_workcomp.c sometimes failed to put the '\0' at the end
of seqc0/seqc1.  Correct bug introduced in fa34t20b3 for fasts34(_t).

>>Oct 9, 2002 CVS tag fa34t20b3

Fix to apam.c build_xascii() to not zero-out qascii[0].  Fix
Makefile.pvm4.  Mix problem with -m 9c with compacc.c.

>>Sept 28, 2002

Additional fixes to -m 9c in p2_complib.c/compacc.c/mshowbest.c.
Remove restriction in fasts34(_t) to less than 30 peptides (though no
more than 30 peptides can be aligned currently).

>>Sept 24, 2002

Fix p2_workcomp.c so that e_scores are delivered correctly when
last_calc flag is set, and -m 9c provides alignments when only one
best hit is present.

Fix comp_lib.c to use different maxn and overlap for each different
query sequence.  fasta34 and fasta34_t now have identical results when
a long sequence is searched.

Add '@C:101' support to memory mapped FASTA format files.

Fix mshowalign.c so that coordinates returned by cal_coord() use
loffset+l_off.

>>Sept 14, 2002	CVS tag fa34t20b2

Changes to p2_complib.c, compacc.c to fix statistics problems with
pv34compfs on query sequences with more than 10 fragments.

>>Aug 27, 2002

Modifications to mshowbest.c and drop*.c (and p2_workcomp.c,
compacc.c, doinit.c, etc.) to provide more information about the
alignment with the -m 9 option.  There is now a "-m 9c" option, which
displays an encoded alignment after the -m 9 alignment information.
The encoding is a string of the form: "=#mat+#ins=#mat-#del=#mat".
Thus, an alignment over 218 amino acids with no gaps (not necessarily
100% identical) would be =218.  The alignment:

       10        20        30        40        50          60         70
GT8.7  NVRGLTHPIRMLLEYTDSSYDEKRYTMGDAPDFDRSQWLNEKFKL--GLDFPNLPYL-IDGSHKITQ
       :.::  . :: ::  .   .:::         : .:    ::.:   .: : ..:.. :::  :..:
XURTG  NARGRMECIRWLLAAAGVEFDEK---------FIQSPEDLEKLKKDGNLMFDQVPMVEIDG-MKLAQ
               20        30                 40        50        60

would be encoded: "=23+9=13-2=10-1=3+1=5".  The alignment encoding is
with respect to the beginning of the alignment, not the beginning of
either sequence.  The beginning of the alignment in either sequence is
given by the an0/an1 values. This capability is particularly useful
for [t]fast[xy], where it can be used to indicate frameshift positions
"/#\#" compactly.  If "-m 9c" is used, the "The best scores" title
line includes "aln_code".

>>Aug 14, 2002	CVS tag fa34t20

Changes to nmgetlib.c to allow multiple query searches coming from
STDIN, either through pipes or input redirection.  Thus, the command

       cat prot_test.lseg | fasta34 -q -S @ /seqlib/swissprot

produces 11 searches.  If you use the multiple query functions, the
query subset applies only to the first sequence.

Unfortunately, it is not possible to search against a STDIN library,
because the FASTA programs do not keep the entire library in memory
and need to be able to re-read high-scoring library sequences.  Since
it is not possible to fseek() against STDIN, searching against a STDIN
library is not possible.

>>Aug 5, 2002

fasts34(_t) and fastm34(_t) have been modified to allow searches with
DNA sequences.  This gives a new capability to search for DNA motifs,
or to search for ordered or unordered DNA sequences spaced at
arbitrary distances.

>>Aug 4, 2002

comp_lib.c has been modified to provide comp_mlib.c function.
comp_mlib.c is no longer used.  comp_lib.c with the "mlib" function
can now recognize protein or DNA sequences automatically, and reads
from stdin can now detect DNA/protein sequence types automatically.
Changes to compacc.c, getseq.c, doinit.c initfa.c, initsw.c, and
nmgetlib.c to support automatic sequence type detection.

>>July 28-31, 2002

(1) The various Makefile's have been "normalized".  The fast*34[_t]
    (Makefile.34m.common[_sql]), Makefile.pvm4[_sql], and
    Makefile.mpi4[_sql] make files all use a common set of filenames,
    described in Makefile.fcom.  This greatly simplifies adding
    programs, but requires that all *.o files be deleted when moving
    from fast*34* to pv34comp* to mp34comp*.

(2) showalign.c/p_showalign.c have been merged into mshowalign.c
    showbest.c/manshowbest.c have been merged into mshowbest.c.  Some
    of the related files (showun.c, manshowun.c, have not been merged
    or tested).

(3) Code for ranking scores with valid e_value's incorporated.

(4) Bug fixes in p2_complib.c, so that fasts34/fasts34_t/pvcompfs
    provide identical statistics.

>>July 26, 2002

Makefile.pvm4_sql and Makefile.pvm4 have been substantially simplified
by providing the worker program name from the h_init() function in the
initfa.c/initsw.c files.

>>July 24, 2002

Substantial modifications to param.h, structs.h to ensure that no
sequence specific information is kept in struct pstruct.  This
structure now holds the pam[] matrix, and other scoring parameters,
but nothing that is dependent on aa0.  The aa0 dependent stuff (nm0,
Lambda, K, etc) is now stored in struct mngmsg.  This was mostly done
to support the pv34comp* programs, which have separate mngmsg
structures but the same pstructs.

The fasts34, fasts34_t, and pv34compfs/c34.workfs have all been tested
successfully.

>>July 19, 2002

Fix an old bug in the calculation of E()-values in DNA databases
longer than 2147483647 residues on machines with 32-bit longs.


>>July 28-31, 2002

(1) The various Makefile's have been "normalized".  The fast*34[_t]
    (Makefile.34m.common[_sql]), Makefile.pvm4[_sql], and
    Makefile.mpi4[_sql] make files all use a common set of filenames,
    described in Makefile.fcom.  This greatly simplifies adding
    programs, but requires that all *.o files be deleted when moving
    from fast*34* to pv34comp* to mp34comp*.

(2) showalign.c/p_showalign.c have been merged into mshowalign.c
    showbest.c/manshowbest.c have been merged into mshowbest.c.  Some
    of the related files (showun.c, manshowun.c, have not been merged
    or tested).

(3) Code for ranking scores with valid e_value's incorporated.

(4) Bug fixes in p2_complib.c, so that fasts34/fasts34_t/pvcompfs
    provide identical statistics.

>>July 26, 2002

Makefile.pvm4_sql and Makefile.pvm4 have been substantially simplified
by providing the worker program name from the h_init() function in the
initfa.c/initsw.c files.

>>July 24, 2002

Substantial modifications to param.h, structs.h to ensure that no
sequence specific information is kept in struct pstruct.  This
structure now holds the pam[] matrix, and other scoring parameters,
but nothing that is dependent on aa0.  The aa0 dependent stuff (nm0,
Lambda, K, etc) is now stored in struct mngmsg.  This was mostly done
to support the pv34comp* programs, which have separate mngmsg
structures but the same pstructs.

The fasts34, fasts34_t, and pv34compfs/c34.workfs have all been tested
successfully.

>>July 8, 2002

Modifications to comp_lib.c, initfa.c and new scaleswt.c, tatstats.c
to support FASTS with Tatusov statistics.

last_params() has been introduced to allow aa0 dependent changes in m_msg/pstr.

sortbest() has been moved into initfa.c/initsw.c to make it function specific.

find_z() takes an additional parameter, escore.

The do_work() results structure, beststr, and stat_str all accommodate
escores as well as integer scores (stat_str also saves segn and segl
but doesn't need them).

In scaleswt.c, process_hist() now knows much more about Tatusov statistics.

last_stats() provided to accommodate rank-based statistical corrections.

scale_scores() is the last function to modify the beststr scores
(final calculation of E-value).

Some sortbest*() calls and some bptr[i]->zscore=find_zp() loops have
been moved into scale_scores();

>>July 3,5, 2002

Modifications to allow mySQL comments (--) in "library.sql 16" files.
Thus, a first line of:

	--host seqdb user password;

is read by FASTA as the login information to a mySQL server, but is
ignored by mySQL.  "DO" commands in FASTA mySQL files can also be
rendered invisible to mySQL in this way.  See "do.sql".

Modifications to mysql_lib.c to allow very long SQL statements.  The
buffer is now dynamically reallocated in 4Kb chunks.

The fasta3.1 man page has been updated and re-organized.

>>June 26, 2002

Minor modifications to nmgetaa.c (openlib()) to use the same arguments
for searching and PRSS.  PRSS needs access to all of m_msg, but
searches do not.  Other small fixes to comp_mlib.c, towards the goal
of merging comp_mlib.c and comp_lib.c.

>>June 25, 2002

Modify the statistical estimation strategy to sample all the sequences
in the database, not just the first 60,000.  The histogram is still
based only on the first 60,000 scores and lengths, though all scores
an lengths are shown.  The fit to the data may be better than the
histogram indicates, but it should not be worse.

Currently, this modification is available only if the -DSAMPLE_STATS
option is defined.

>>June 23, 2002	CVS fa34t11d4

Fix a very long-standing bug in fasty/tfasty that caused 'NNN' to be
translated as 'S', rather than 'X'.  fastx/tfastx has done this
correctly for many years, but the fasty/tfasty code that I received
from Zheng Zhang was not implemented correctly (my fault, his code was
fine).

>>June 19, 2002

Added "-C #" option, where 6 <= # <= MAX_UID (20), to specify the
length of the sequence name display on the alignment labels.  Until
now, only 6 characters were ever displayed.  Now, up to MAX_UID
characters are available.

>>May 30, 2002	CVS fa34t11d3

Fixed problem with programs using the default -E cutoff when -b was
provided.  With this implementation, -E can override -b, but -b
overrides the default -E.

Fixed problem with 64-bit file offsets in param.h (change USE_FSEEK0
-> USE_FSEEKO, include -D_LARGEFILE_SOURCE and -D_LARGEFILE64_SOURCE
in Makefile.linux_sql).  Put limits on alignment display length (200
chars).  More checks for null returns from SQL queries.

>>Apr 17, 2002	CVS fa34t11d2

Fixed bug in mm_file.h/ncbl2_mlib.c that caused the SGI version to be
unable to read blast2 format files.

Changed "mp_*" tags to "pg_*" for -m 10 option.

>>Mar 30, 2002

Fix embarrassing bug in revcomp() (getseq.c) that failed to complement
the central nucleotide in a sequence with an odd number of residues.

Small changes to dropfs.c for more segments.

>>Mar 16, 2002

Added create_seq_demo.sql, nt_to_sql.pl to show how to build an SQL
protein sequence database that can be used with with the mySQL
versions of the fasta34 programs.  Once the mySQL seq_demo database
has been installed, it can be searched using the command:

	fasta34 -q mgstm1.aa "seq_demo.sql 16"

mysql_lib.c has been modified to remove the restriction that mySQL
protein sequence unique identifiers be integers.  This allows the
program to be used with the PIRPSD database.  The RANLIB() function
call has been changed to include "libstr", to support SQL text keys.
Due to the size of libstr[], unique ID's must be < MAX_UID (20)
characters.

A "pirpsd.sql" file is available for searching the mySQL distribution
of the PIRPSD database.  PIRPSD is available from
ftp://nbrfa.georgetown.edu/pir_databases/psd/mysql.

>>Mar 6, 2002

Fix showbest.c showbest() to report pst.zdb_size as database size.
Fix dropnfa.c spam() to address off-by-one on end of run, and double
counting on backwards scan.  Fix dropnfa.c do_fasta() to fix another
problem introduced by -S.  Changes to comp_lib.c to ensure that both
the beginning and end of the query and library sequence have '\0'
present.  Changes to initfa.c, initsw.c to ensure that a match to a
lower-case letter with -S gets exactly the same score as a match to an
'X'.  Changes to mmgetlib.c to work with 64-bit longs in *.xin files.

>>Feb 26, 2002

Fixes to doinit.c, initfa.c, initsw.c to allow DNA matrices using the
"-s dna.mat" option.  A new matrix, "d50ry.mat" is available that
scores +5 for a match, -2 for a transition, and -5 for a
transversion. "d50ry.mat" corresponds to DNA PAM50 with transitions
twice as common as transversions.  When "-s dna.mat" is used, "-n"
MUST be used as well.

Query sequence names ("aa", "nt") should be more accurate.

>>Feb 22, 2002

Fix to getseq.c to allow "plain" sequence files.

>>Feb 12, 2002

Minor fix to res_stats.c.

>>Jan 28, 2002

Fixes to resurrect res_stats.c.  res_stats (cc -o res_stats
res_stats.c scaleswn.c -lm) takes the output from a current "-R
file.res" file and calculates statistical significance - this allows
one to take exactly the same set of scores (and lengths) and calculate
statistical estimates using different strategies.

>>Jan 24, 2002

modifications to mmgetlib.c, ncbl2_mlib.c to more robustly read memory
mapped files (*.xin, map_db) on machines lacking "native" 64-bit
longs.  If the machine provides some definition for a 64-bit long
(e.g. "long long", "int64_t"), things should work. 64-bit offsets into
memory mapped files work properly on Alpha, SGI, i386 Linux, and
MacOSX.  The current implementation depends either on 64 bit longs
(Compaq Alpha's pre 4.0G) or the <sys/inttype.h> file.  Makefile,
Makefile.alpha, and Makefile.linux have been modified.

Modifications to nmgetlib.c, mmgetlib.c to provide GI numbers and
Accession versions for Genbank searches.  If the GI:123456 number is
available, it will be used and the description line will be formatted:

	gi|123456|gb|ACC1234.1|LOCUS description

This should help FAST_PAN runs, where the version of a sequence
changes frequently.

>>Jan 10, 2002

Modifications to p2_complib.c, p2_workcomp.c to more reliably allocate
space for library sequence descriptions on the master and workers.

>>Jan 2-3, 2002		CVS fa34t10c/fa34t10d3

Fixes to comp_lib.c to support Macintosh and Windows/Turbo-C
compilation.  New Makefile.tc.  Macintosh version supports both
"Classic" and "Carbon" environments.

"<values.h>" has been replaced with the more modern "<limits.h>"

Fixes to p2_complib.c to support n_libstr (libstr length) in GETLIB().

comp_thr.c, complib.c removed.

>>Dec 16, 2001

Complete integration of comp_mlib.c with both the unthreaded and
threaded programs.  Comp_mlib allows fasta34 and fasta34_t to compare
a database with a second database, just as pv34compfa does.  Using
multiple queries with fasta34_t is not as efficient as pv34compfa (and
it cannot use networks of Unix workstations), but it is much easier to
use and install.

With the comp_mlib.c option, fasta34 cannot automatically recognize
DNA sequences, just as pv34compfa no longer recognizes DNA sequences.
You must use the "-n" option to search with DNA sequences.  The other
programs (fastx34, tfastx34, etc) "know" the type of the query and
database sequences, so "-n" is only required for fasta34(_t).

>>Dec 14, 2001		CVS tag fa34t10b

Fix problems reading DNA databases in blast2 format.

>>Dec 11, 2001

Changes to spam() in dropnfa.c so that, for DNA sequences, the
previous behavior for finding the boundaries of a local alignment
region use the same algorithm as previous versions of fasta.  For
protein sequences, the algorithm will extend the local region beyond
the "ktup" boundaries if a better score can be found.  For DNA
sequences, this raises the noise rather than increasing sensitivity,
so it is turned off and "ktup" boundaries are respected.  The old,
"ktup" boundary algorithm is available with -DNOSPAM_EXT.

This version also includes a working res_stats.c, which can be used to
test various statistical estimates on exactly the same set of scores.

Fixed problems with -m 9 percent identity for fastx/fasty/tfastx/tfasty.
These errors have been present since -m 9 was implemented.

>>Dec 10, 2001

Fix to map_db.c to work correctly with files > 2 Gb when 64-bit longs
are available.  It is not yet designed to work with ftello() and other
offset types.

>>Nov 11,21, 2001	CVS tag fa34t10a, fa34t10d1

Substantial changes to revcomp(), getseq(), and other functions to
correct problems with -S on DNA sequences.  Sequences with lower case
nucleotides were not recognized or reverse complemented properly.

Fix to dropnfa.c (v34t07, Nov 21, 2001) bg_align() to re-initialize
static globals - this fixes a problem encountered with pv34compfa.  A
new main program, comp_mlib.c has been added to the CVS archive,
although it is not referenced in any of the Makefile.  comp_mlib.c
works like p2_complib.c and compares a library against another
library.

>>Nov 4, 2001

Change to dropnfa.c spam () while(1) -> while(lpos <= dmax->stop).
This fixes a problem with ktup=1 on Suns only, so far.

>>Oct 4, 2001		CVS tag fa34t10

Add comp_lib.c file, which merges complib.c (unthreaded) and
comp_thr.c (threaded) code into one file.

Modifications to nmgetlib.c, mmgetaa.c to allow Genbank flatfile
format without DESCRIPTION or ACCESSION lines.

Additional fix for -S with ktup=1.

>>Sept. 24, 2001

Fix to have correct gap-penalties for short scoring matrices with
tfastx/fastx.

>>Sept. 10, 2001	CVS tag fa34t05d6

Fix a bug introduced by -S fix in fa34t05d5.  Also, try to remove
changes in p34compfa compared to pv4compfa output.

>>Sept. 6, 2001		CVS tag fa34t05d5

Fix the -S dropnfa/fx/fz2 bug that was not actually fixed in
fa34t05d4.  Incorporate the correct scaleswn.c refered to in
fa34t05d4.

>>Sept. 5, 2001		CVS tag fa34t05d4

Fix problem with m_msg.quiet that prevented interactive prompts for
ktup, file name, etc with threaded programs.

Fix serious bug in dropnfa.c/dropfx.c/dropfz2.c that caused -S to work
improperly on sequences with effective length of 3 or less.

Change to scaleswn.c to make mle_cen(), mle_cen2() more robust to cases
where the top and bottom scores are the same.

Change p2_complib.c to avoid compiler complaints with (void *)wstage2p=NULL
on some platforms.

>>Aug. 30, 2001		CVS tag fa34t05d3

Fixed problem with uthr_subs.c for Suns, but changed Makefile.sun to
use pthreads rather than Sun Unix threads.  Removed SQL stuff from
Makefile.mpi4/pvm4 and added Makefile.mpi4_sql/pvm4_sql.

fa34t05d2 - fix to map_db.c to provide *sascii.

fa34t05d1 - fixes to ibm_pthr_subs.c and Makefile.ibm from IBM.

>>Aug. 20, 2001		CVS tag fa34t05d0

The pvm/mpi complib programs have been substantially updated with
release 3.4.  See readme.v34t0 for more information.  With version
3.4, the MPI programs are mp34comp*, mu34comp*, etc.

A major effect of this change is to disable automatic sequence type
(protein/DNA) recognition with pv34compfa/mp34compfa.  By default,
protein libraries are assumed.  Thus, pv34compfa/mp34compfa require
the "-n" command line option when running pv34compfa/mp34compfa on DNA
sequence libraries.  This issue does not occur with the other
programs, which will recognize the appropriate sequence type, because
it is determined by the program (e.g. pv34compfx requires
DNA:protein).

Fixed substantial problem with 64-bit file offsets for Linux in
complib.c/comp_thr.c, p2_complib.c.  This problem, solved by Doug
Blair, was preventing the threaded versions from working properly in
memory mapped mode.

In all earlier versions of fasta, when very long sequences were
searched, the sequence length reported was that of the "chunk" that
was actually searched (typically 80,000-query_length) rather than the
actual library sequence length.  The peculiar behavior now changed,
and the full length of the library sequence, not the sequence chunk,
is reported as the library sequence length.  Note that chunks are
still used, however, which can cause the same alignment to be shown
twice.  In addition, the "-m 9" output format has changed to report
the coordinates of the query and library sequence (see below), which
may be different from 1-sequence_length because the the query and
library sequences may have been extracted from larger sequences.  Four
additional fields have been added, "pn0", "px0","pn1", "px1" that are
the positions in for the beginning (pn0/1) and end (px0/1) of they
query/library sequence.  pn0/1 would typically be changed with the
"@C:#" directive, described below.

Changes to doinit.c/initfa.c/initsw.c to provide a new function -
f_lastenv() - that allows function-specific adjustments to parameters
after the command line options have been read but before the first
sequence is read.  This change solved problems with "mp/pv34compfx -S".

fasts34/tfasts34 now recognize that 'I/L' are the same, as are 'Q/K'
(which are apparently indistinguishable by Mass-Spec).  The latter
identity is on by default, but can be turned off with "-h 0".

The MPI/PVM versions of the programs have been tested extensively with
compfa, compfx, and comptfx.  Makefile.mpi4 now works properly.
Changes to p2complib.c to support the PVM option "-T 1-4", which
allows one to run on nodes 1-4 of a (presumably larger) PVM virtual
machine.  This option has no effect on the mp34comp* programs.  The
old "-T 4" to run on 4 nodes, is also available.  If each node has 2
cpu's, as indicated in the "pvmd hostfile", both CPU's will be used
for a total, in this example, of 8 processes. This allows one to
specify a large PVM machine and use separate parts of it
independently.

Changes to nmgetlib.c to fix problems with longer dates in GCG files
(Y2K).  Fixes to faatran.c for extended alphabets and 'X's.  Various
code clean-ups to make "gcc -Wall" a little bit (not much) happier.

This is the first distributed fasta34 version.

================
>>Aug 9, 2001		CVS tag fa34t05

Corrections to initfa.c to allow -S to work with tfastx/y.
Fix to manshowbest.c for query position with -m 9.

>>July 18, 2001		CVS tag fa34t04

Various changes to complib.c, comp_thr.c, p2_complib.c, showbest.c,
showalign.c to deal with overlapping alignments in long sequences that
have been segmented.  When long sequences are segmented (lcont>0), the
eventual total length (n1tot_v) is saved at beststr->n1tot_p.  If
there was no lcont, then beststr->n1tot_p = NULL, and beststr->n1
should be used as the sequence length.  This has the advantage of
requiring space only when long sequences are encountered, and
requiring only one integer for several segments.

m_msg.noshow has been removed.

The -m 9 format has been changed - 5 fields have been added, 4
(pmn0/pmx0/pmn1/pmx1) provide the beginning and end coordinates of the
query and library sequence; the last (fs) reports the number of
frameshifts.  The names of the alignment boundaries have been changed
from min0/max0/min1/max1 to amn0/amx0/amn1/amx1 (Alignment miN/maX).

The SQL format has been extended to provide for statements that do
things but do not generate results, such as creating and selecting into a temporary table, e.g.:
================
    do
    create temporary table seq_pos (
    id int unsigned not null auto_increment primary key,
    prot_id int unsigned not null default 0,
    start int unsigned not null default 0,
    length int unsigned not null default 0,
    )
    ;
    do
    insert into seq_pos (prot_id, start, length)
      select id, 11, len-10
      from protein, annot
      where len > 100
      and annot.protein_id = protein.id
      and annot.pref=1
    ;
    select seq_pos.id,
       substring(protein.seq, start, length),
       concat("@C:", start, " ", descr)
    from protein, seq_pos, annot
    where protein.id = annot.protein_id
      and protein.id = seq_pos.prot_id
      and annot.pref = 1
    ;
    select prot_id,
       concat("@C:", start, " ", descr)
    from seq_pos, annot
    where annot.protein_id = seq_pos.prot_id
      and seq_pos.id = #
      and annot.pref = 1
     ;
================

  In the current implementation, these statements must start with "DO"
as the first two characters on the line, and come immediately after a
line ending with ';'.  The text from "DO" to the next ";", excluding
the "DO", is executed when the database connection is made.

===== >>July 12, 2001

The allocation of the work_info data structure used to send
information to the worker threads has been changed.  The old method
worked, possibly by accident.

A bug in p2_complib.c that caused E()-values to be calculated
improperly for the first query sequence has been fixed.

>>July 11, 2001	--> fa34t02

It is now possible to specify output coordinates in library sequences
by including the string: "@C:number" on the description line, e.g.

   >gtm1_human gi|12345 human glutathione transferase M1 @C:21

would label the first residue in the library sequence "21" rather than
"1".  This capability has been included to provide accurate
coordinates for searches done against subsequences generated by an SQL
query.  For example, one could use a query of the form:

 SELECT protein.id, substring(protein.seq,11,length(protein.seq)-20),
	concat(protein.name," @C:11 ",protein.descr)
 FROM protein;

to generate a sequence set with each sequence starting with residue
11.  Without the "@C:11" option on the description line, the program
would number the alignment positions starting at 1, even though the
first residue of the sequence really started at 11.  "@C:11" allows
one to correct the coordinate system.

Currently, "@C:offset" is available only with library type 1 (fasta
format) and 16 (mySQL).

The SQL-generated database with "@C:offset" can be used with both the
fast*34(_t) programs and with pv34comp*.  However, the SQL syntax is
used differently in the fasta34 and pv34compfa programs.  fast*34(_t)
requires three SQL statements during a search: (1) a statement to
generate a large set of library sequences; (2) a statement to generate
a description of a single sequence, given a unique identifier provided
by (1); and (3) a statement to generate a single sequence given a
unique identifier provided by (1).  For fast*34 searches, the third
(3) SQL statement must provide the "@C:offset" information in the
third results field for the offset to be used.  It is optional in (1)
and (2).

The pv34comp* programs only require one SQL statement, statement (1)
above, which must provide three fields, a unique identifier, the
sequence, and a complete description that must include "@C:offset" if
substrings are used.  If SQL queries (2) and (3) are provided, they
are  ignored.  Thus, the same files can be used by both programs, but
the "@C:offset" is required in different SQL queries by the fast*34
and pv34comp* programs.

Other changes:

Re-incorporation of GAP_OPEN option; fix to Altschul-Gish stats when
GAP_OPEN is used.

Re-incorporation of A. Mackey's spam() improvement in dropnfa.

Fixes to include file ordering to allow fast*34(_t) pv34comp* programs
to compile.

Fix to lascii[] for SQL database queries.

Fix to an old bug in comp_thr.c to send individual worker_info
structures to threads (does not fix LINUX threads problems, however).

=====
>>July 9, 2001

Considerable changes to support no-global library functions.

(1) Separate ascii/sequence mapping arrays are used by the
    query-reading (qascii), library-reading (lascii), and sequence
    comparison function (pascii) routines.  As a result, there is no
    longer a need for tgetlib.o/lgetlib.o - lgetlib.o can serve both
    functions.

(2) This also allows us to remove all #ifdef TFAST/FASTX conditionals
    from complib.c/comp_thr.c/p2_complib.c.  We no longer need
    tcomp_thr.o, comp_thrx.o, etc.  We still have a variety of
    p2_complib.o variations to support the different c34.work* files.

(3) Because non-global openlib/getlib functions are available, exactly
    the same open/get functions are available for reading both the
    query and reference libraries in pv34comp* programs.  The
    host-specific openlib/getlib functions in hxgetaa.c are now
    provided by nmgetlib.c, etc. This has two effect:

    (a) it is now possible to compare a query database generated by an
        SQL query to a library database generated by a different SQL
        query.

    (b) pv34comp* has lost (at least in this version) the ability to
        automatically detect the query sequence type. To search with a
        DNA query, you MUST use "-n".

(4) the resetp() function is now responsible for almost all of the
    function sepcific (TFAST/FASTX/etc) initializations.  All of the
    function specific code has been removed from complib.c/comp_thr.c
    and most of it has been moved to initfa.c/resetp().

(5) manageacc.c has been merged into compacc.c (mostly prhist()).

=====
>>June 1, 2001

Many changes to accommodate a new - no global variable - strategy for
reading sequence databases.  Every time a file is opened, a struct
lmf_str is allocated which can be used for memory mapped files, ncbl2,
files, and mysql files.

In addition, an open'ed file has a default sequence type: DNA or
protein, or one can open a file in a mode that will allow the sequence
type to be changed.

=====
>>May 18, 2001		CVS: fa33t09d0

A new compile time parameter - -DGAP_OPEN, is available to change the
definition of the "-f gap-open" parameter from the penalty for the
first residue in a gap to a true gap-open penalty, as is used in BLAST
and many other comparison algorithms.  This will probably become the
default for fasta in version 3.4.

Fixes to conflicts between "-S" and "-s matrix".  When a scoring
matrix file was specified, lower-case alignments were not displayed
with -S (although the scores were calculated properly).

More extensive testting of mysql_lib.c (mySQL query-libraries) with
the pv4comp* and mp4comp* programs.

=====
>>April 5, 2001		CVS: fa33t08d4b3

Changes in nmgetlib.c and ncbl2_mlib.c to return long sequence
descriptions for PCOMPLIB (pv4/mp3comp*).  Also fix p2_complib.c to
request DNA library for translated comparisons.

Fix for prss33(_t) to read both sequences from stdin.

=====
>>March 27, 2001	CVS: fa33t08d4

Modifications to allow 64-bit fseek/ftell on machines like Sun,
Linux/Intel, that support -D_FILE_OFFSET_BITS=64, -D_LARGE_FILE_SOURCE
off_t, and fseeko(), ftello() with the option -DUSE_FSEEKO.  Machines
with 64-bit long's do not need this option.  Machines with 32-bit
longs that allow files >2 Gb can do so with 64-bit file access
functions, including fseeko() and ftello(), which work with off_t file
offsets instead of long's.

=====
>>March 3, 2001		CVS: fa33t08d2

Corrected problems in nmgetaa.c and mysql_lib.c with parallel
programs, and one serious problem with alternate DNA scoring matrices
(initfa.c, initsw.c) not being set properly.  A subtle problem with
the merge of scaleswn.c and scaleswg.c is fixed.

>>February 17, 2001

Modified mysql_lib.c to use "#", rather than "%ld", to indicate the
position of the GID.  This change was made because sprintf() cannot be
used reliably to generate an SQL string, as '"' and '%' are used in
such strings.

=====
>>January 17, 2001
(no version change, date change)

Minor fixes to initfa.c, initsw.c to deal with DNA scoring matrices
properly. "-n -s dna.mat" is required for the sequence/matrix to be
recognized as DNA.

>>January 16, 2001
-->v34t00

Merge of the main CVS trunk - fa33t06 with the latest release branch,
fa33t08.

In addition, PCOMPLIB mods have been made to mysql_lib.c.  Because
p2_complib.c gets sequence description information during the first
read of the database, the mysql_query must be changed to return:
result[0]=GID, result[1]=description, result[2]=sequence.  In the
PCOMPLIB case, the other SQL queries (for GID description, sequence)
are not necessary but must still be provided.

  $Id: readme.v35 120 2010-01-31 19:42:09Z wrp $
  $Revision: 55 $

>>Sep. 10, 2008

Fix problem in init_ascii() call for p2_complib2.c.

>>Sep. 9, 2008

Fix bug in display of library name when written to an output file
(rather than stdout).

>>Aug. 28, 2008		fa35_04_02	SVN Revision: 45

Fix serious bug in alignment generation that only occurred when large
libraries were used as a query with [t]fast[x/y].  This bug often
resulted in a core dump.

Address some other issues with uninitialized variables with -m 9c.

>>Jul. 15, 2008		fa35_04_01	SVN Revision: 38

Correct problems with Makefiles.  Add information on compiling to README.
Address issue with mp_KS for -m 10 when searching small libraries.

>>Jul. 7, 2008		fa35_04_01	SVN Revision: 35

Fix problems that occurred when statistics are disabled with -z -1,
both for a normal library search, and for searches of a small library.

>>Jul. 3, 2008	  	  	SVN Revision: 33

Continue to fix an issue with 'J' and -S.

>>Jun. 29, 2008     	 	SVN Revision: 29, 31

Fix additional problems with Makefiles, some issues uncovered with
Solars 'C' compiler (Rev. 30).

Discover serious bug when searching long, overlapping sequences, such
as genomes.  The length of the library sequence was not updated to
reflect the length of the new region plus the overlap.

Fix inconsistency in the value of 'J' between uascii.h/aascii[] and
pascii[].  Add code to ensure that lascii[], qascii[], never return a
value outside pam2[][] (all <= pst.nsq) (particularly for 'O' and 'U'
amino-acids).

exit(0) returns for map_db, list_db.

>>Jun. 11, 2008

Correct bug in scaleswn.c that prevented exact matches to queries < 10
residues from being scored and displayed.

>>Jun. 1, 2008

Address various cosmetic issues in FASTA output:

(1) Modify comp_lib2.c so that -O outfile works when multiple queries are
compared in one run.

(2) remove the duplicated query sequence length in the 1>>>query line.

(3) in -m 10 output, the tags "pg_name" and "pg_ver" were duplicated, e.g.

>>>K1HUAG, 109 aa vs a library
; pg_name: fasta35_t
; pg_ver: 35.03
; pg_argv: fasta35_t -q -b 10 -d 5 -m 10 ../seq/prot_test.lseg a
; pg_name: FASTA
; pg_ver: 3.5 Sept 2006

The ; pg_ver and ; pg_name produced by the get_param() functions in
drop*.c have been renamed ; pg_ver_rel and ; pg_ver_alg.

>>>K1HUAG, 109 aa vs a library
; pg_name: fasta35_t
; pg_ver: 35.03
; pg_argv: fasta35_t -q -b 10 -d 5 -m 10 ../seq/prot_test.lseg a
; pg_name_alg: FASTA
; pg_ver_rel: 3.5 Sept 2006

Modify mshowbest.c, mshowalign.c to highlight E() values (<font
color="dark red"></font> in HTML output.

>>Apr. 16, 2008     fa35_03_07

Merge fa35_ann1_br, which allows annotations in library sequences.

The PVM/MPI parallel version now support query sequence annotations
and -m 9c annotation encoding.  It does not yet support library
annotations.  Tested with both PVM and MPI.

>>Apr. 2, 2008	    fa35_03_06

Ensure that code in last_init() to modify ktup never increases ktup value.

Add fasta_versions.html to more explicitly describe programs available.

>>Mar. 4, 2008

Fix parsing of parameters (matrix, gap open, gap ext) in ASN.1 PSSM
files produced by blastpgp.

>>Feb. 18, 2008	  fa35_03_05

Re-implement -M low-high sequence range options.  Sequence range
restriction has probably been missing since the introduction of
ggsearch and glsearch, which use a new approach to limiting the
sequence range.

>>Feb. 7, 2008	  fa35_ann1_br

Add annotations to library sequences (they were already available in
query sequences).  Currently, annotations are only available within
sequences, but they should be available in FASTA format, or any of the
other ascii text formats (EMBL/Swissprot, Genbank, PIR/GCG).  If
annotations are present in a library and the annotation characters
includes '*', then the -V '*' option MUST be used.  However, special
characters other than '*' are ignored, so annotations of '@', '%', or
'@' should be transparent.

In translated sequence comparisons, annotations are only available for
the protein sequence.

The format for encoded annotations has changed to support annotations
in both the query and library sequence.  If the -m 9c flag is provided
and annotations are present, then an annotated position in the
alignment will be encoded as:

 '|'q-pos':'l-pos':'q-symbol'l-symbol':'match-symbol'q-residue'l-residue'

For example:

    |7:7:@@:=YY|14:14:##:=TT

In cases where the query or library sequence does not have an
annotation, then the q-symbol or l-symbol will be 'X' (which is not a
valid annotion symbol).

>>Jan. 25, 2008	   fa35_03_04

Map 'O' (pyrrolysine) to 'K', 'U' (seleno-cysteine) to 'C' in uascii.h
('J' is already recognized and mapped to the average of 'I' and 'L').
Thus, 'J' will appear in alignments, but 'O' and 'U' are transformed
to 'K' and 'C'.

Because "Oo" and "Uo" are not (currently) part of aax[] ("Uu" is in
ntx[]), apam.c/build_xascii() was extended to add characters from
othx[] - "oth" for "other" so that they are not lost.

Double check, and fix, some mappings for 'J/j' and 'Z/z'.

>>Jan. 11, 2008	   fa35_03_03

Clean up some issues with -m 10 output; put "; mp_Algorithm", ";
mp_Parameters" down with other -m 10 ";" lines.  Also provide ";
al_code" and "; al_code_ann" if -m 9c is specified.  Remove duplicate
">>>query" line.

Add "; aln_code" and "; ann_code" to -m 10 -m 9c output.  The
alignment/annotation encoding is only produced once (in showbest(),
and is then saved for -m 10 aligment.

>>Dec. 13, 2007	  fa35_03_02m (merge of fa35_03_02 and fa35_02_08_br)

Add ability to search a subset of a library using a file name and a
list of accession/gi numbers. This version introduces a new filetype,
10, which consists of a first line with a target filename, format, and
accession number format-type, and optionally the accession number
format in the database, followed by a list of accession numbers.  For
example:

	  </slib2/blast/swissprot.lseg 0:2 4|
	  3121763
	  51701705
	  7404340
	  74735515
	  ...

Tells the program that the target database is swissprot.lseg, which is
in FASTA (library type 0) format.

The accession format comes after the ":".  Currently, there are four
accession formats, two that require ordered accessions (:1, :2), and
two that hash the accessions (:3, :4) so they do not need to be
ordered.  The number and character after the accession format
(e.g. "4|") indicate the offset of the beginning of the accession and
the character that terminates the accession.  Thus, in the typical
NCBI Fasta definition line:

 >gi|1170095|sp|P46419|GSTM1_DERPT Glutathione S-transferase (GST class-mu)

The offset is 4 and the termination character is '|'.  For databases
distributed in FASTA format from the European Bioinformatics
Institute, the offset depends on the name of the database, e.g.

 >SW:104K_THEAN Q4U9M9 104 kDa microneme/rhoptry antigen precursor (p104).

and the delimiter is ' ' (space, the default).

Accession formats 1 and 3 expect strings; accession formats 2 and 4
work with integers (e.g. gi numbers).

>>Dec. 12, 2007  fa35_02_08

Correct bug in ssearch35 gapped scores that only occurred in
non-accelerated code.  This bug has been present since fa35_02_06.
Modified the Makefiles so that accelerated (ssearch35(_t)) and
non-accelerated (ssearch35s(_t)) are available. Edited Makefile's to
provide accelerated ssearch35 more specifically.

Modifications to provide information about annotated residues in the
-m9c coded output. Previously, -m 9c output added a field:

    =26+9=15-2=9-1=3+1=74-2=3-3=63

after the standard -m 9 output information.  With the new version, an
annotated query sequence ( -V '*#' ) adds the field:

    |14:16:#<TM|24:26:#>TA|44:37:*>ST|71:66:#=TT

which indicates that residue 14 in the query sequence aligns with
residue 16 in the target (library) with annotation symbol '#', the
alignment score is '<' less than zero, and the residues are 'T'
(query) and 'M' (library). (The '|' is used to separate each
annotation entry.)

>>Nov. 10, 2007

Parts of p2_complib.c and p2_workcomp.c, and the pvm/mpi Makefiles,
have been updated to be consistent with name changes in the param.h
and structs.h directories.

>>Nov. 20, 2007   fa35_02_08

Parts of p2_complib.c and p2_workcomp.c, and the pvm/mpi Makefiles,
have been updated to be consistent with name changes in the param.h
and structs.h directories.

>>Nov. 6, 2007	  fa35_02_07

Correct problems with asymmetric RNA matrices in initfa.c and rna.mat.

>>Oct. 18, 2007

Correct problem parsing ASN1 FastaDefLines when the database is local.

Recovering from a misplaced cvs commit of code that was supposed to be
on a branch, code has been recovered from earlier versions (fa35_02_05
because fa35_02_06 has some branch contamination).

>>Oct. 4, 2007	  fa35_02_06

Correct error in gap penalties in dropnnw.c.  Due to an unfortunate
inconsistency, the gap parameter in FLOCAL_ALIGN (in dropgsw2.c) had a
different meaning than that in almost all the other programs (it was
the sum of gap_open and gap_ext).  The FLOCAL_ALIGN function call was
copied for FGLOBAL_ALIGN, even though the the FGLOBAL_ALIGN function
used the more conventional gap_open, gap_ext parameters.  Thus,
FGLOBAL_ALIGN was wrong and the subsequent do_walign() in dropnnw.c
were wrong.  dropgsw2.c:FLOCAL_ALIGN has been modified to use the
conventional gap_open parameter, and calls to dropnnw.c:
FGLOBAL_ALIGN() and do_walign() have been fixed.

>>Sept. 20, 2007

Modify the logic used when saving a seq_record *seq_p into beststr
*bbp to ensure that if the seq_record is replaced, it is replaced at
all the places where it is referenced.  This involves adding a linked
list into beststr (*bbp->bbp_link).  When making the link (and freeing
it up), be certain that the linked seq_p is the same as the one being
replaced.

>>Sept. 18, 2007   fa35_02_05

A relatively obscure problem was found on the SGI platform when
searching a library smaller than 500 sequences (thus requiring some
shuffles). Two bugs were found and corrected; one involved not
allocating aa1shuff with COMP_THR and not do a m_file_p->ranliba()
before re_getlib().  The second involved destroying a pointer to the
list of seq_records when a sequence was being shuffled.  The bugs were
confirmed with Insure, and have been fixed.

>>Sept. 7, 2007	fa35_02_04

Revamp the offset handling code to provide better uniformity between
query and library offsets and coordinate systems.

Fix a problem with load_mmap() to load 64-bit sequence locations
properly on machines with 32-bit integers.

>>Sept. 4, 2007

Modify ncbl2_mlib.c slightly to check to see whether the amino-acid
mapping in blast databases is identical to the FASTA mapping (it
should be).  If they are identical, do not re-map the blast amino acid
sequences (potentially a small speed up).

>>Aug. 22, 2007

Change ps_lav.c to lav2ps.c, and add lav2svg.c.  It is now possible to
generate a lalign35 HTML output that has both SVG (lav2svg) and PNG
(lav2ps | gs ), graphics.

>>Aug. 10, 2007	CVS fa35_02_03

Fix faatran.c:aacmap() bug.

>>Aug. 6, 2007

Extensive restructuring of pssm_asn_subs.c to parse PSSM:2 ASN.1's
downloaded from NCBI WWW PSI-BLAST more robustly.

>>July 25, 2007	  CVS fa35_02_02

Change default gap penalties for OPTIMA5 matrix to -20/-2 from -24/-4.

>>July 24, 2007

Correct bugs introduced by adding 'J' - 'J' was initially put before
'X' and '*' in the alphabet, which led to problems because the
one-dimensional lower-triangular pam[] matrices (abl50[], abl62[],
etc) had entries for 'X', and '*', but not for 'J'.  By placing 'J'
after the other characters, the problem is resolved.

Modify tatstats.c to accommodate 'J'.

'*' is back in the aascii[] matrix, so that it is present by default
(like fasta34).

>>July 23, 2007

Changes to support sub-sequence ranges for "library" sequences -
necessary for fully functional prss (ssearch35) and lalign35.  For all
programs, it is now possible to specify a subset of both the query and
the library, e.g.

    lalign35 -q mchu.aa:1-74 mchu.aa:75-148

Note, however, that the subset range applied to the library will be
applied to every sequence in the library - not just the first - and
that the same subset range is applied to each sequence.  This probably
makes sense only if the library contains a single sequence (this is
also true for the query file).

Correct bugs in the functions that produce lav output from lalign35 -m
11 to properly report the begin and end coordinates of both sequences.
Previously, coordinates always began with "1".  Correct associated bug
in ps_lav.c that assumed coordinates started with "1".

>>June 29, 2007	CVS fa35_02_01

Merge of HEAD with fasta35 branch.

>>June 29, 2007	CVS fa35_01_06

Add exit(0); to ps_lav.c for 0 return code.

>>June 26, 2007

Add amino-acid 'J' for 'I' or 'L'.

Add Mueller and Vingron (2000) J. Comp. Biol. 7:761-776 VT160 matrix,
"-s VT160", and OPTIMA_5 (Kann et al. (2000) Proteins 41:498-503).

Changes to dropnnw.c documentation functions to remove #ifdef's from
strncpy() - which apparently is a macro in some versions of gcc.

>>June 7, 2007

Modify initfa.c to allow ggssearch35(_t), glsearch35(_t) to use PSSMs.

>>June 5, 2007  CVS fa35_01_05

Modifications to p2_complib.c, p2_workcomp.c to support Intel C
compiler.  Fixed bug in p2_workcomp.c - gstring[2][MAX_STR] required -
[MAX_SSTR] too short.  mp35comp* programs now tested and working (as
are pv35comp*, c35.work* programs).

Fix problem with fasts/fastm/fastf last_tat.c with limited memory.

Correct problem with lalign35.exe Makefile.nm_[fp]com.

Add $(CFLAGS) to map_db to enable large file support.

Address problem with PSSM's when '*' not defined (initfa.c:extend_pssm()).

>>May 30, 2007	CVS fa35_01_04

Complete work on ps_lav, which converts an lalign35 lav (-m 11) file
into a postscript plot, which looks identical to the plots produced by
plalign from fasta2.  (ps_lav has been replaced by lav2ps and lav2svg).

>>May 25,29, 2007

Changes to defs.h, doinit.c mshowalign.c for -m 11, which produces lav
output only for lalign35.

Changes to comp_lib2.c to add m_msg.std_output, which provides all the
standard print lines.  This is turned off for -m 11 (lav) output.
lalign35 -m 11 provides standard lav output, with the addition of
#lalign35 -q ... .

>>May 18, 2007

Add m_msg.zsflag to preserve pst.zsflag when reset by global/global
exclusion of many library sequences.

>>May  9, 2007	CVS fa35_01_03

Tested local database size determination with p2_complib2/p2_workcomp2.

>>May 2, 2007	renamed fasta35, pv35comp, etc

Separate thread buffer structures from param.h.

Problems with incorrect alignments has been fixed by re-initializing the
best_seqs and lib_buf2_list.buf2 structures after each query sequence.

The labels on the alignment scores are much more informative (and more
diverse).   In the past, alignment scores looked like:

>>gi|121716|sp|P10649|GSTM1_MOUSE Glutathione S-transfer  (218 aa)
 s-w opt: 1497  Z-score: 1857.5  bits: 350.8 E(): 8.3e-97
Smith-Waterman score: 1497; 100.0% identity (100.0% similar) in 218 aa overlap (1-218:1-218)
^^^^^^^^^^^^^^

where the highlighted text was either: "Smith-Waterman" or "banded
Smith-Waterman". In fact, scores were calculated in other ways,
including global/local for fasts and fastf.  With the addition of
ggsearch35, glsearch35, and lalign35, there are many more ways to
calculate alignments: "Smith-Waterman" (ssearch and protein fasta),
"banded Smith-Waterman" (DNA fasta), "Waterman-Eggert",
"trans. Smith-Waterman", "global/local", "trans. global/local",
"global/global (N-W)".  The last option is a global global alignment,
but with the affine gap penalties used in the Smith-Waterman
algorithm.

>>April 24, 2007

The new program structure has been migrated to the PVM and MPI
versions.  In addition, the new global algorithms (pv35compgg,
pv35compgl) have been moved, though the the PVM/MPI versions do not
(yet) to the appropriate size filtering.

>>April 19, 2007

Two new programs, ggsearch35(_t) and glsearch35_t are now available.
ggsearch35(_t) calculates an alignment score that is global in the
query and global in the library; glsearch35_t calculates an alignment
that is global in the query and local, while local in the library
sequence.  The latter program is designed for global alignments to domains.

Both programs assume that scores are normally distributed.  This
appears to be an excellent approximation for ggsearch35 scores, but
the distribution is somewhat skewed for global/local (glsearch)
scores.  ggsearch35(_t) only compares the query to library sequences
that are beween 80% and 125% of the length of the query; glsearch
limits comparisons to library sequences that are longer than 80% of
the query.  Initial results suggest that there is relatively little
length dependence of scores over this range (scores go down
dramatically outside these ranges).

A bug was found and fixed in showalign() and showbest() where the
aa1save buffer was not preserved when some sequences needed to be
re-read, while others were stored in the beststr.

>>April 9, 2007

Some of the drop*.c functions have been reconfigured to reduce the
amount of duplicate code.  For example, dropgsw.c, dropnsw.c, and
dropnfa.c all used exactly the same code to produce global alignments
(NW_ALIGN() and nw_align()), this code is now in wm_align.c.
Likewise, those same files, as well as dropgw2.c, use identical code
to produce consensus alignments (calcons(), calcons_a(), calc_id(),
calc_code()).  Rather than working with three or four copies of
identical code, there is now one version.

>>March 29, 2007

At last, the lalign (SIM) algorithm has been moved from FASTA21 to
FASTA35.  Currently, only lalign35 is available.  A plotting version
will be available shortly (or perhaps a more general solution that
produces lav output).

The statistical estimates for lalign35 should be much more accurate
than those from the earlier lalign, because lambda and K are estimated
from shuffles.

Many functions have been modified to reduce the number of times
structures are passed as arguments, rather than pointers.

>>February 23, 2007

The threading strategy has been modified slightly to separate the end
of the search phase (and a complete reading of all results buffers)
from the termination phase.  This will allow future threading of
subsequent phases, including the Smith-Waterman alignments in
showbest() and showalign() (though care will be required to ensure
that the results are presented in the correct order).

>>February 20, 2007	fasta-34_27_0  (released as fasta-35_1)

The FASTA programs have been restructured to reduce the differences
between the threaded and unthreaded versions (and ultimately the
parallel versions) and to make more efficient use of modern large
memory systems.  This is the beginning of a move towards a more robust
shuffling strategy when searching databases with modest numbers of
related sequences.

The major changes:

  comp_lib.c -> comp_lib2.c  - comp_lib.c will be removed
  work_thr.c -> work_thr2.c  - work_thr.c will be removed

  mshowbest.c, mshowalign.c have been modified to remove aa1 as an
    argument. They must allocate that space if they need it.

  The system is set up to allocate a substantial amount of library
  sequence memory, either to a single buffer (unthreaded) or to the
  threaded buffer pool.  For smaller databases, the library sequences
  are read once, and then subsequently read from memory (this could be
  extended for RANLIB(bline) as well).

Soon, these changes will allow the program to re-read the beststr[]
sequences and shuffle them to produce accurate lambda/K estimates.

================================================================

See readme.v34t0 for earlier changes.

================================================================

  $Id: readme.v36 1291 2014-08-28 18:32:58Z wrp $
  $Revision: 55 $

Version 3.6 of the FASTA programs is a significant update over version
3.5.  It uses the same underlying structure as FASTA35 (specifically
the strategies for ensuring accurate statistics), but it allows for
multiple high-scoring alignments to be shown, rather than just one.
This is the main functional difference between FASTA and BLAST -
BLAST could show multiple HSPs, FASTA did not.

>>Jul. 21, 2015 [fasta-36.3.8]
[compacc2e.c, cal_cons2.c, dropfx2.c dropfz3.c, param.h]
Fixed a major bug in the annotation code that had been added to
accomodate overlapping domains.  The original implementation was not
thread-safe, because the array of annotations was modified during the
scoring, but was also shared by threads.  The new version keeps
independent scoring arrays.

>>Jun. 23, 2015 [released as fasta-36.3.7b]
[dropnnw2.c]
Fix problem where glsearch reset (ignored) the -M sequence limit.

>>Jun. 18, 2015
[dropfx.c, dropgsw.c, dropfx.c, dropfx2.c, dropfz3.c]
Fix problem in do_walign.c with comparison to score_thresh during
recursive alignment.

>>May. 21, 2015
[compacc2e.c]
Add additional checks to ensure that annotations are within the
sequence boundaries.

>>Jan. 26, 2015	[ re-released as fasta-36.3.7a]
[compacc2e.c]
Fix problem with domain boundary calculations for subsets of sequences.

>>Jan. 21, 2015	[ released as fasta-36.3.7a]
[calc_cons2.c, dropfx2.c, dropfy3.c]
Fix problems with -m 9c / -m 9C alignment encodings in version
36.3.7. Apparently, the Nov. 25, 2014 fix was not committed properly.
In addition, make certain that the query sequence is ALWAYS the
reference sequence, particularly in translated alignments. As a
result, the insertion/deletion codes are now reversed for fast[xy]36
and tfast[xy]36.

>>Jan. 6, 2014
[data/VTML_*.mat]
Provided scoring matrix files for the VTML_10,20,40,80,120,160,200
matrices available internally.

>>Nov. 25, 2014	[ released as fasta-36.3.7]
[cal_cons.c, dropfx2.c, dropfz3.c]
Fix problem that prevented -m 9c and -m 8CC unless annotations were
present.

Added approved copyright notice and Apache 2.0 license to
appropriate files.

>>Nov. 19, 2014
[mshowbest.c]
Add alignment (CIGAR) string and annotation string to BLAST tabular
(-m 8) aligments with -m 8C[cCdD].  To get alignment and annotation
encoding without BLAST comments, use -m 8X[cCdD].

>>Nov. 10, 2014
[cal_cons2.c, dropfx2.c, dropfz3.c]
Ensure that site annotations are shown when annotations are embedded
in a sequence, not provided by a script.

>>Oct. 27, 2014
[cal_cons2.c]
Fix a bug in the annotation alignment that put annotation symbols off
by one (or more) in the coordinate lines. Add annotations that align
in gaps.

>>Oct. 6, 2014
[most source files]
The copyright notice for fasta-36.3.7 has been updated to include an
open software license, Apache2.0, for redistribution.

>>Sept. 28, 2014
[url_subs.c]
Substitute annot_p->s_annot_arr_p[] for annot_p->domain_arr_p[i] in
display_domains(), encode_json_str().  Remove domain_arr_p from struct
annot_entry.  With domain_arr_p gone, n_domains is less useful, but it
is still available, and used for checking for domain graphics.
encode_json_domains() also now uses annot_p->n_annots, and skips over
non-domains.

>>Sept. 19, 2014
[dropfx2.c, dropfz3.c]
Fixes to produce correct coordinates with forward and reverse
complement [t]fast[x,y].

>>Sept. 17, 2014 [new version, fasta-36.3.7]
[compacc2e.c, cal_cons2.c, dropfx2.c, dropfz3.c]
The annotation domain scoring/plotting strategy has been extended to
allow overlapping domains.  To accommodate overlapping domain
annotations, the annotation file format (e.g. gstm1_human.annot) has
been extended to accept the form:

>sp|P09388|GSTM1_HUMAN
1	-	88	Glutathione_S-Trfase_N :1
7	V	F	Mutagen: Reduces catalytic activity 100- fold.
90	-	208	Glutathione-S-Trfase_C-like :2
108	V	Q	Mutagen: Reduces catalytic activity by half.

where a "-" in the second field indicates that the first and third
fields specify the beginning and end of the domain. In previous
versions, a '[' specified the beginning of a domain, and a ']' on a
later line specified the end of the domain. '[' and ']' on separate
lines required that domains not overlap (so that the '[' and ']' could
be paired).  fasta-36.3.7 will still read this format, but the "start -
stop" format is both simpler and more flexible.

Three new annotation scripts are available that use the new domain
notation: ann_feats2ipr_e.pl, ann_feats_up_www2_e.pl, ann_pfam_e.pl,
and ann_pfam_www_e.pl.  All four scripts will report overlapping
domains.

Overlapping domains also allows domain annotations from different
sources to be combined (e.g. InterPro Pfam, Panther, and Superfamily
domain annotations), as well as domain annotations of different types,
e.g. Uniprot domain and secondary structure annotations.

>>Aug. 28, 2014	[re-released as fasta-36.3.6f]
[ncbl2_mlib.c]
The code used to parse blastfmtdb sequence description lines has not
kept up with NCBI's use of ASN.1 in sequence descriptions.  This code
has been updated, and now works properly with the protein and DNA
sequence databases.

[comp_lib9.c]
Fixed a seg-fault that occurred when an open-file error occurred.

>>Aug. 22, 2014	[released as fasta-36.3.6f]
[mshowbest.c]
Change alignment summary display for lalign to not show identical
alignment score unless '-J' option used.  Add "The best non-identical
alignments" when no "-J"

[ann_pfam_www.pl] Fix bugs.

[ncbl2_mlib.c]
modified to read NCBI ambiguity codes in
blastdbfmt/formatdb nucleotide databases.  Not extensively tested.`

>>Aug. 20, 2014
[compacc2.c, cal_cons.c, dropfx.c, dropfz2.c]
Modify sub-alignment score report to calculate bit-score by dividing
total alignment bit score by sub-alignment raw score divided by total
alignment raw score.  This produces a bit score that is much more
sensible than the previous strategy, which calculated a z-score from
the sub-alignment.

>>Aug. 18, 2014
[compacc2.c, cal_cons.c]
Undo removal of '[]' from aa0a/aa1a (they are required to visualize
domain boundaries in alignment).  cal_cons.c now users PSSMs when they
are available.

>>Aug. 8, 2014
[comp_lib9.c, compacc2.c]
Move the call to get query annotations via scripts out of compacc2.c
and into comp_lib9.c.

>>July 29,2014
[comp_lib9.c, mshowbest.c, mshowalign2.c]
Enable high scoring alignment display (like high scoring sequences)
with lalign36, when -m 9 (-m 9c/d/C/D) option is provided, or with -m
8.  This allows lalign36 to provide a compact, tabular list of
non-overlapping local alignments.

>>June 30, 2014
[pssm_asn_subs.c]
Update the code for parsing ASN.1 binary PSSM files produced by
psiblast+. The new code reads more of the optional fields in
pssm_intermediate_data().  The fields are not used, but broke the
earlier parser.

>>June 11, 2014
[cal_cons.c, initfa.c, dropfx.c, dropfz2.c]
Extend the match/mismatch encoding provided by -m 9c and -m 9C with -m
9d and -m 9D.  The -m 9d/D options provide mismatch locations as well
as insertion/deletion locations.  For -m 9d, the list of codes has
expanded from '=\/*' to '=\/*x'; for -m 9D, 'MDIMX'.  Current
implementation works for all programs except [t]fast[fms].  Updated
version strings to June, 2014.

>>May 28, 2014
[mshowalign2.c, mshowbest.c, initfa.c, structs.h]
Add the command line option -XI.  Changes the calculation of percent
identity to ensure that a single mismatch in a long sequence with >
99.9\% identity is displayed as 99.9% (0.999) identity, rather than
100.0% identity. Without this option, a single mismatch in 10,000
residues displays 100% identity, with the option, 99.9% identity is
displayed (even though the identity is 99.99%).

[cal_consf.c]
Fix the false error message "code begins with 0" in cal_consf.c.

>>Feb. 12, 2014
[compacc2.c]
When providing "sequence length" to annotation scripts, add offsets.
Also modify scripts to allow sequence lengths to increase.

>>Jan. 28, 2014  (re-released as fasta-36.3.6d/Jan 2014)
[dropfs2.c, calconsf.c, tatstats.c]
The coordinate fix for fasts36/fastm36 (Dec 18, 2013) broke some
fasts/fastm alignments. The alignment code has been reverted to the
"classic" code that has been used for more than 10 years.  However,
that code always marked the first aligned residue as 1, even when the
first part of the query did not align.  The initial coordinate offset
has been fixed; the coordinate is now the position in the first
aligned fragment.  This may be confusing, because with fasts, the
first aligned fragment may not be the first fragment in the query
list.  The coordinate provided always provides the offset from the
beginning of the first fragment in the alignment, not the first
fragment in the list.  This fix required changes to the definition of
calc_astruct(), which required changes to build_ares.c, mshowalign.c,
calc_cons.c, dropfx.c, and dropfz2.c.

>>Jan. 24, 2014
[mshowalign2.c]
Add checks to assumption that '>gi|12345' is an NCBI library entry.
[nmgetlib.c]
Fix for nmgetlib.c with -DMYSQL_DB

Some cleanup of old Makefiles.

>>Jan. 1, 2014
[url_subs.c]
Fix off by one in domain coordinates in display_domains().

>>Dec. 18, 2013
[dropfs2.c, cal_consf.c]
Fix problem with alignment display when query sequence is much longer than library sequence.

>>Dec. 11, 2013
[compacc2.c]
Modified save_best2() to correctly exclude sequences outside
-M n1_low-n1_high limits.

>>Nov. 8, 2013   (re-released as fasta-36.3.6d)
[ncbl2_mlib.c]
Fix problem with src_long8_read() where int/uint64_t seems to cause
problems with Linux intel icc. Using int/unsigned int solves the problem.

>>Nov. 1, 2013
[apam.c, ncbl2_mlib.c, map_db.c]
[apam.c ] Fix problem with query sequences and libraries that do not
end in newline ('\n').  [ncbl2_mlib.c, map_db.c] provide grouping for
shifts for byte extraction in src_int4/long8_read() to remove compiler
warnings.  [map_db.c] Fix problem reading sequences for indexing that
caused crash.

>>Oct. 8, 2013	 (released as fasta-36.3.6d)
[comp_lib9.c, initfa.c]
Modify initfa.c/re_ascii() function to avoid qascii[] characters that
had been remapped for annotations.

>>Oct. 4, 2013
[nmgetlib.c, ncbl2_mlib.c]
Modify nmgetlib.c/re_openlib() to re-use memory mapped file arrays.
This had been the intention for some time, but a check for libf != 0
prevented the memory mapped arrays from being reused.  libf is no
longer checked, just mm_flag.

>>Sep. 26, 2013
[ncbl2_mlib.c]
Fix a bug in ncbl2_mlib.c/parse_fastadl_asn() that prevented
accessions longer than 20 characters in description lines from BLAST
formatted libraries.

[compacc2.c]
Fix a bug in compacc2.c/comment_var() that showed the wrong original
sequence in qVariant changes.

>>Sep. 2, 2013
[dropfs2.c]
Fix bug in dropfs2.c/init_work() that prevents correct tatusov
statistics with -z >10.

>>Aug. 21, 2013  (released as fasta-36.3.6c)
[comp_lib9.c]
Fix bug in comp_lib9.c/new_seqr_chain() that prevented memory from
being allocated to the chain if a memory mapped database was followed
by a non-memory mapped database.

>>Aug. 9, 2013
[scaleswn.c]
Ensure shift to MLE_STATS if too many scores are excluded by trimming.

>>July 31, 2013 (released as fasta-36.3.6b)
[url_subs.c]
Make JSON output for -m 6 (html) dependent on $ENV{JSON_HTML}. JSON
output is not currently used.

>>July 26, 2013
[mshowalign2.c, scripts/lavplt_svg.pl]
Correct offsets in -m 11 lav plots, and modify lav2plt.pl/
lavplt_svg.pl/ lavplt_ps.pl to reflect the corrections.

Move all perl scripts out of /src into /scripts.

>>July 19, 2013 (released as fasta-36.3.6a)
[compacc2.c, cal_cons.c, dropfx.c, dropfz2.c, build_ares.c]
Provide dynamic string allocation/dyn_strcat for annotation string
output. This fixes problems with long proteins with many domains or
other annotations, which were too long for the fixed annotation output
storage.

Version date updated to July, 2013.
Compiled and tested on Windows32.

>>July 8, 2013
[cal_cons.c, dropfx.c, dropfz2.c]
Properly terminate annotions with offsets [cal_cons.c], and with
domains beyond alignment [dropfx.c, dropfz2.c]

>>July 5, 2013	 (released as fasta-36.3.6)
[comp_lib9.c, doinit.c, dropfx.c, dropfz2.c]
Fix conflict between -m 9 and -z -1; fix annotation display using
non-script annotations. Stop using calc_last_set in dropfx/fz2.c.

>>June 24, 2013
[scripts/ann_feats_up_www2.pl]
Add script (ann_feats_up_www2.pl) for annotating UniProt sequences using:
"http://www.ebi.ac.uk/Tools/dbfetch/dbfetch/uniprotkb".

>>June 6, 2013
[compacc2.c, cal_cons.c, initfa.c, dropfx.c, dropfz2.c]
Provide the -XNS/-XXS/-XN+/XX+ and -XND/-XXD/-XN-/-XX- options that
specify how N:N and X:X alignments are counted for similarity and
identity.  By default, N:N (DNA) and X:X (protein) alignments are
considered identical, but not similar (because their scores are
typically negative to address statistical issues).
-XNS/-XXS/-XN+/-XX+ cause N:N/X:X alignments to be counted as similar,
even though their alignment are negative.  Likewise,
-XND/-XXD/-XN-/-XX- cause N:N and X:X alignments to be considered
non-identical (and non-similar).

>>May 28, 2013
[url_subs.c]
do_url1() has been modified to: (1) require env($REF_URL, $SRCH_URL,
$SRCH_URL1) for these links to produce printout.  (2) Link text is
surrounded by <!-- LINK_START "lname" --> <!-- LINK_STOP -->.  (3)
do_url1() now produces <!-- JSON --> output automatically, which can
be used to get all the information provided by earlier URL links.

>>May 29, 2013
[mshowalign2.c]
Re-instate code in showalign() to ensure that original bbp->rst is
used for first alignment, rather than that calculated by CHECK_SCORE
(which is used for later sub-HSP's).  The CHECK_SCORE -S alignment
score is based on the non-S alignment, and is then re-scored with the
low-complexity -S matrix. But the best alignment excluding
low-complexity can have a higher score than the best all-complexity
alignment rescored with -S.

>>May 27, 2013
[mshowalign2.c, url_subs.c]
The plot_domain.cgi SVG code has been expanded to allow the domain
structure of the entire query and library sequence, not just the
aligned regions, to be displayed.  Showing domains above the query or
below the library takes an additional 18 px in each direction (36
total); this size needs to be provided in the <object data=""
width="660" height="54"> format string that is provided in
$DOMAIN_PLOT_URL.

Right now, the argument to $DOMAIN_PLOT_URL can get very long with
lots of aligned domain (region), and query and library domain
information.  It would be better to provide this in some separate way.
YAML might also be a more efficient strategy.

>>May 9, 2013
[dropfx.c, dropfz2.c, compacc2.c, url_subs.c]
The web infrastructure for domain plots has been completed --
plot_domain2.cgi which generates SVG for domain plots now understands
reverse-complement cDNA fastx/y alignments, and plots coordinates
accordingly.  Testing with fastx36/fasty36 revealed some memory
errors, which have been fixed.  In addition, dropfz2.c has been
updated to properly treat some region/alignment-boundary conditions;
dropfx.c and dropfz2.c provide equivalent sub-alignment scores.

[../scripts, ../misc]
A new directory, ./scripts, has been created to collect the scripts
used for sequence library expansion and domain/feature annotation.
../scripts/README.scripts provides more information.  Modify code to
allow expansion scripts (-e) to start with '\!', like annotation
scripts.

>>Apr. 15, 2013
(compacc2.c, cal_cons.c, dropfx.c, dropfz2.c, mshowalign2.c)
Modifications to properly deal with sequence and coordinate offsets in
annotation alignments.  compacc2.c/get_annot_list() has been modified
to only print/read an annotation once (the same sequence may appear
twice with fastx/fasty).  mshowalign2.c now includes <!--
ANNOT_START/STOP --> and <!-- ALIGN_START/STOP --> in HTML mode.  This
comments are not on their own line, to save output space, so the
remainder of the line should be captured.

>>Apr. 5, 2013
(doinit.c)
Add the ability to specify HTML output using the -m '0H' option.  This
addresses the problem that -m "F6" does not fully specify the output
format.  In addition, -m 6 should probably explicitly set -m 0 (if it
has not been set), rather than simply 'or'ing it, but right now we do
not know when it is set.

>>Mar. 17, 2013
(compacc2.c, url_subs.c, plot_domain.cgi, ann_feats2l.pl)
Modifications to url_subs.c to support SVG domain maps in HTML output.

A new evironment variable has been defined, DOMAIN_PLOT_URL, which can
be used to plot (using SVG or PNG) a map of the domains on the library
sequence.  The argument to DOMAIN_PLOT_URL is the concatenated list of
annotations provided by the -V options.  All annotations (including
sites) are passed; non-alpha-numeric characters are URL encoded.
plot_domain.cgi is an example of a script that can be passed as
DOMAIN_PLOT_URL.  To use this script:

$ENV{DOMAIN_PLOT_URL}="<object data=\"plot_domain.cgi?n0=%d&query=%s&db=%s&lib=%s&q_start=%ld&q_stop=%ld&l_start=%ld&l_stop=%ld&n1=%d&o_pgm=%s&doms=%s\" width=\"660\" height=\"72\"></object>\n";

ann_feats2l.pl has been extended to allow the --neg
(or --neg-dom) option, which puts domain a NODOM domain annotation
between the domain annotations provided by the database.

>>Mar. 7, 2013
(cal_cons.c)
Modify update code to properly begin global alignments that start with
insertions or deletions.

>>Feb. 20, 2013
(compacc2.c)
Annotation scripts (-V \!ann_feats.pl) were being inactivated if no
annotations were returned, fixed.

>>Feb. 2, 2013
(comp_lib9.c)
Prevent premature termination of query title in -m 9 mode (guarantees
the full >accession text to first space is preserved).
(compacc2.c)
Provide domain information (;C=PF00016) in -m9 domain scoring.

>>Jan 7-9, 2013
(initfa.c, pssm_asn_subs.c)
Modify pssm_asn_subs.c to properly parse binary PssmWithParameters
produced by NCBI asntool from psiblast (blast+) text ASN.1 output.
The text ASN.1 uses a binary encoded query sequence; get_lambda() in
initfa.c was modified to work with a binary encoded query sequence
(the query is used to find the p_i from rrcounts[query[i]]).

Modify pssm_asn_subs.c to set query=NULL when PSSM does not include
query sequence.  Modify read_asn_pssm() to set query=aa0 if query==NULL;

>>Dec. 14, 2012
(cal_cons.c, dropfx.c, dropfz2.c)
Enable percent identity calculation on domains.  Merge
cal_cons.c/calc_code() strategies into dropfx.c, dropfz2.c

>>Dec. 6, 2012
(comp_lib8.c, comp_lib9.c, nmgetlib.c)
Fix code in close_lib_list() that did not properly re-initialize files
for re-reading (not seen when library is in memory, or for single
sequence search).

>>Dec 2, 2012
(wm_align.c, Makefiles)
CHECK_SCORE() in wm_align.c must return different scores for local and
global (#define GGSEARCH in wm_align.c).  Requires modified Makefiles.

>>Sep 24, 2012
(doinit.c, compacc2.c, cal_cons.c)
Fix bugs introduced with next_annot_entry() strategy for reallocating
annot_arr[]; find a bug in cal_cons.c where i1_annot was indexing
annot0_arr_p[]; ensure that m_msg.ann_arr_def[] is appropriately initialized.

>>Sep 17, 2012
(lav2plt.pl, lavplt_ps.pl, lavplt_svg.pl, lav_defs.pl, l_feat_dom.pl)
Convert the lav*.c programs to perl.  This simplifies adding the
ability to script domain annotation.  The format for domain
annotations for the lav2plt.pl programs differs slightly from the
current up_feats_dom.pl program, because it requires a beginning and
end for each domain, e.g.:

>sp|Q14247.2|SRC8_HUMAN
80	[]	116	Cortactin 1.
117	[]	153	Cortactin 2.
154	[]	190	Cortactin 3.
191	[]	227	Cortactin 4.
228	[]	264	Cortactin 5.
265	[]	301	Cortactin 6.
302	[]	324	Cort. 7; trunc.
492	[]	550	SH3.

and takes a single accession from the command line, e.g.:
"l_annot_dom.pl sp|P09488" rather than reading a file.

>>Sep 4, 2012
(doinit.c, compacc2.c, fasta_guide.tex)
Annotations can now be provided within a sequence (-V '%#!'), by a
script (-V '\!up_feats.pl'), or from a file (-V '<annot.file
q<annot.file').  Annotation files make particular sense for query
annotations, where the user may know much more about the query than
the database does.

(doinit.c, compacc2.c, comp_lib9.c, structs.h)
Ensure that calc_code() is called if any -m 'F9c file' requires it.

>>Aug 31, 2012
(cal_cons.c, compacc2.c, dropfx.c, dropfz2.c)
The region score calculations have been corrected to include regions
that overlap alignment boundaries, and regions that start in gaps.

>>Aug 10, 2012
(cal_cons.c, compacc2.c, dropfx.c, dropfz2.c)

Introduce a second kind of annotation feature, the "Region" (denoted
by '[' and ']'), that specifies a region that should be scored
separately.  These regions cannot be nested, each residue can belong
to only one region.  However, the scores in these regions can be
calculated (perhaps percent identity and length later), and are
displayed:

>>sp|P09488|gstm1_human GLUTATHIONE S-TRANSFERASE MU 1 (  (218 aa)
 Site:* : 23Y=23Y : MOD_RES: Phosphotyrosine (By similarity).
 Site:* : 33Y=33Y : MOD_RES: Phosphotyrosine (By similarity).
 Site:* : 34T=34T : MOD_RES: Phosphothreonine (By similarity).
 Region : 3-82 : score=547; bits=146.4 :  GST_N
 Site:^ : 116Y=116Y : BINDING: Substrate.
 Region : 104-171 : score=465; bits=125.8 :  GST_C

All information about the region should be provided with the '['
(start) symbol.

>>Aug 1, 2012
(dropfx.c, dropfz2.c, c_dispn.c)
Fix some very old bugs that caused errors in coordinate displays of
reverse-complement fastx/fasty alignments.  Fix BLAST alignment
display coordinates.  Enable variant calculations for FASTY
(dropfz2.c), and simplify calculations for dropfx.c

>>Jul 29,2012
(doinit.c, compacc2.c, comp_lib9.c)
Allow annotation descriptions to be delivered by annotation script,
denoted by '=' in first line, e.g.:
=*:phosphorylation
=^:binding site
=@:active site
>gi|121735|sp|P09488.3|GSTM1_HUMAN
7	V	F	Mutagen: Reduces catalytic activity 100- fold.
23	*	-	MOD_RES: Phosphotyrosine (By similarity).
33	*	-	MOD_RES: Phosphotyrosine (By similarity).
34	*	-	MOD_RES: Phosphothreonine (By similarity).

remove requirement for leading space before annotation script: e.g.:
-V '\!up_feats_c.pl'

>>Jul 27, 2012
(compacc2.c, cal_cons.c, dropfx.c)

(1) Allow comments/descriptions on features other than type 'V' (variant)
to be displayed with alignment.  If a '@' SITE feature has a comment
provided by the annotation script, the comment will be displayed in
the alignment description , e.g.:

>>sp|P28161.2|GSTM2_HUMAN Glutathione S-transf            (218 aa)
 ^ :116Y=116Y: BINDING: Substrate (By similarity).
 @ :210S+210T: SITE: Important for substrate specificity.
 initn: 632 init1: 632 opt: 632  Z-score: 1414.3  bits: 268.8 E(450603): 2.6e-71
Smith-Waterman score: 945; 75.2% identity (93.6% similar) in 218 aa overlap (1-218:1-218)

If no comment is provided, the annotation will only appear in the
coordinate line. This provides a way to show annotation locations in
BLAST output.

(2) Also add code to ensure that symbols returned by annotation scripts
are displayed on the coordinate line.

(3) Add environment variable substitution to =${TMP_D}/annot.defs and
\!${TMP_D}/up_feats_c.pl parsing.

>>Jul 24, 2012
(uascii.h, map_db.c)
Modify NANN, a value one more than the largest amino-acid encoding
value, increasing it from 50 (too small for NCBIStdaa_ext_n) to 60;
ESS changed to 59.

>>Jul 20, 2012
(mshowalign2.c, mshowbest.c, compacc2.c, comp_lib8.c)
(transferred from fasta-36.3.5)
(a) Fix bug in mshowalign2.c that occurred because of re-use of the
"tmp_len" variable when adding '\n' to -L long descriptions.  This
typically occurred with -m 10.  (b) Modify logic used to capture if an
alignment had been calculated, reducing dramatically the number of
re-alignments with multiple -m "F" output files.

>>Jun 30, 2012
(mshowbest.c)
Ensure that opt score and E()-value are based on initial scan score,
not later alignment score.  score_delta is used to increment initial
scan score.  However, currently the E()-value of the alignment score
is displayed in the alignment list, so the -m 9 and showalign()
E()-values can be inconsistent.

>>Jun 29, 2012 (from fasta-36.3.5c)
(pssm_asn_subs.c)
Add chk_asn_buf() before getting RPSPARAMS_MATRIX.

>>Jun. 27, 2012 (from fasta-36.3.5c))
(nmgetlib.c, compacc2.c)
Fix bug that allocated unnecessary space for re-loading sequences in
pre_load_best() (compacc2.c).  Ensure that closed/NULL memory mapped
file descriptors are not returned.

>>Jun. 18, 2012
(compacc2.c)
Modify pre_load_best() to allocate memory for sequences to be aligned
only if the sequences are not already in memory.  (Searches against
hg18 with repetitive queries caused very large amounts of memory to be
allocated in duplicate.)

>>Jun. 12, 2012
(compacc2.c, doinit.c, dropfx.c, cal_consf.c)
Implement variant scoring for fastx36.  Also address problems with
annotation location when -m markx is not set.  Check function
definitions for other drop functions where variant scoring is not yet
implemented.

>>Jun. 9, 2012
(defs.h, doinit.c, c_dispn.c)
Add 'M' and 'B' options to -m 0,1 to specify annotation location. For
example, -m 0M (-m1) causes the annotation to be inserted in the
"middle" alignment line, rather than in the coordinate line (making
the sequence with the annotated feature ambiguous).  -m 0B, -m1B
puts the annotation in both the middle (alignment) line and the
coordinate line.

>>Jun. 8, 2012
(doinit.c, compacc2.c, build_ares.c, mshowbest.c, mshowalign2.c,
structs.h and others)

Implement a script-driven strategy for feature annotation in
alignments.  In addition to: fasta36 -V '*%^@', which extracts the
annotation characters from the library sequences, we can also do:
fasta36 -V '*%^@ \!feature_script.pl' which expects the same
annotation characters ('*%^@'), but expects them from the script
'feature_script.pl'.  This script gets the sequence description line,
e.g: "gi|121746|sp|P09211|GSTP1_HUMAN Glutathione S-transferase P (GST
class-pi) (GSTP1-1)", and is expected to return a tab-delimited file:
====
pos label value
23	*
33	*
34	*
116	^
173	V	N
210	V	T
====

Currently, the "value" is ignored unless the label is "V", for
variant. If 'V' annotations are present, then the alternative
amino-acid residue values are tested in alignments; if the variant
residue improves the score, the score is updated and the variant
sequence is displayed, and a 'V' indicates the variant in the
coordinate line.  Currently, variant annotations can only affect
library sequences.

By default, annotation symbols are shown in the coordinate line for -m
0 (default) and -m 1 (difference) alignments, sometimes overwriting
the coordinate. Annotation symbols (from either sequence) can be shown
in the middle alignment line by specifying -m 0M or -m 1M, or in both
the middle alignment line and the coordinate line with -m 0B, -m 1B.

>>May 5, 2012
(dropnnw2.c)
Enable rev-comp for ggsearch/glsearch.

>>Mar. 13, 2012
(defs.h)
Increase default file name length to 256 from 120 to accommodate long
file names at the EBI.  Also allow much longer command line arguments
argv_line[MAX_LSTR=4096] to be reported.

>>Jan. 30, 2012
(nmgetlib.c, altlib.h)
Read .fastq sequence libraries (ignoring quality information) as library type '7';

>>Dec. 21, 2011 (released as fasta-36.3.5c)
(nmgetlib.c)
Fixed a problem reading multiple library files that produced
segmentation faults because a data buffer was free()ed and then
re-used.

>>Nov. 17, 2011
(initfa.c, mshowalign.c)  (from fasta-36.3.5b)
Fix problem with ppst->e_cut_r for LALIGN DNA sequences (set
improperly to 0.001).  Add ':' to s_bits: in -m 10 output.  Also
remove "score" from "lsw_s-w opt" score description (not present in
non-LALIGN -m 10).

>>Nov. 9, 2011 (from fasta-36.3.5b)
(lavplt_svn.c, lavplt_ps.c, ncbl2_mlib.c)
Fix buffer overrun for lav legend.  Fix old problem re-opening NCBI
blastdbfmt indirect OID files.

>>Oct. 30, 2011
(comp_lib9.c)
Correct re-initialization bug that prevented the second query sequence
from seeing the entire library.

[from fasta-36.3.5a_svn]
(comp_lib9.c, comp_lib8.c, ncbl2_mlib.c, nmgetlib.c)
Address out-of-memory problems when searching memory mapped, and fix
problem using fopen()/fread() rather mmap for NCBI DNA databases.  On
32-bit machines, NCBI database files cannot be left open, and are now
more agressively closed.  However, searches that produce very large
numbers of alignments may still run out of memory on low-memory 32-bit
machines.

(compacc2.c, comp_lib8.c, comp_lib9.c, htime.c)
Correct problems that produce negative scan times.

>>Oct. 21, 2011
(pcomp_subs2.c, work_thr2.c, mshowalign2.c, make/Makefile.mp_com2, Makefile.fcom)
Fixes to re-enable MPI compilation and execution.

>>Oct. 18, 2011
(compacc2.c, mshowbest.c, comp_lib8.c, comp_lib9.c, initfa.c)
Fix the logic for specifying the number of alignments displayed with
the -b 123, -b '>123', -b '=123', -b '$' options, particularly when
statistics are not used.

>>September 21, 2011
(initfa.c, apam.c, scaleswn.c compacc2.c)
Two major problems have been addressed (which also affect fasta-36.3.5
and earlier versions): (a) specifying a -s dna.mat DNA matrix did not
work properly; (b) too few shuffles, particularly with DNA sequences,
were produced with pairwise comparisons.  The problem with scoring
matrix files was exacerbated by the use of fixed library alphabets.
initfa.c has been modified to recognize that when a DNA scoring matrix
is specified, the "-n" option is set.  The shuffling problem appeared
when, for pairwise DNA comparisons, fewer than 50 shuffles were
reported. This occurred because the buffers used to communicate with
threads no longer have a fixed amount of sequence buffer associated
with them.

>>August 23, 2011
(tatstats.c, upam.h, apam.c)
The remapping of the amino-acid encoding to NCBIstdaa broke some
assumptions in tatstats.c, and elsewhere.  In addition to the simple
mapping problem, which changed the counts[] assignment in
tatstats.c/calc_priors(), the fact that NCBIstdaa does not have
contiguous real amino acids (e.g. B is at position 2), broke the
generate_tatprobs() function because of a very old bug where priorptr
was not always incremented.

Some of the drop*.c functions have been updated to ensure that the
space allocated for rapid pam[][] score lookup includes space for
lower-case characters, which can be present in pseg'ed "map_db -b"
libraries.  In addition, binary format (currently all mmap'ed)
libraries cannot include annotations, because common annotation values
('*', '&') overlap the range of the NCBIstdaa_l (lowercase) mapping.

>>August 1, 2011
(map_db.c)
map_db.c has been modified to provide a more efficient memory mapping
for FASTA format files. map_db -b works like map_db, but, in addition
to writing the .xin index file of descriptions and sequences in the
FASTA library, it also produces a new protein_library.bsq file and
protein_library.xin_b that contains binary encodings of the databases
and an index for this file.  The binary encoding can be memory mapped,
so that database searches can proceed directly from memory.  map_db -b
.bsq files are very similar to the blastfmtdb files, except that they
accomodate lower-case letters (masked) in the sequences.  The
implementation of blastfmtdb lower-case masking prevents it from being
used in directly memory mapped files.

map_db.c introduces a new memory mapped format encoding, MP2.  I
expect this format to be extended to allow not only directly memory
mapped files, but also directly memory mapped lookup tables.  A
database can be hashed, and the hash and link files written to a
library file, which can then be used for searches without the need to
re-calculate the hash/link tables.

(comp_lib9.c, mmgetaa.c, ncbl2_mlib.c, initfa.c, dropfz.c)
Modifications to allow memory mapped files to be read and processed
directly.  Databases with lower-case characters can be memory mapped,
which means that lower-case characters are coming into the alignment
programs even when -S is not specified.  As a result, all the protein
scoring matrices must be built-out to allow lower-case
characters. Likewise, the dropfz2.c matrices built by init_weights()
must always be set for lower-case characters.

>>July 20, 2011
(mshowbest.c, mshowalign2.c)
gi|12345 numbers are no longer shown in the list of best hits unless
-m 8 or -m 9 are used.  They are never shown in the alignments.
(dropfz2.c)
Modify MAX_UC, MAX_LC to be consistent with NCBIstdaa alphabet. Modify
<= nsq for init_weights().

>>July 16, 2011	 fasta-36.3.6
(comp_lib9.c, drop*.c, cal_cons*.c)
The internal encoding of amino-acids has changed to NCBIstdaa
throughout the programs.  This allows the programs to use memory
mapped NCBI blastdbfmt libraries directly, without re-encoding, but
lower-case low-complexity mapping is not recognized.  This allows
substantial speedup in single query searching.  However, to allow
low-complexity searches, a new memory mapped format/encoding will be
required.

>>July 5, 2011	 fasta-36.3.6
(compacc2.c)
Modify save_best2() logic for identifying scores to be used for
statistics.  An is_valid_stat is set for multi-frame results that
specify which scores can be used for the stats[] and qstats[] arrays.
Modifications to buf_do_work(), buf_shuf_work(), and buf_qshuf_work()
to cause the calculation to be done in the thread, rather than the
main program.  Fix some bugs in the qshuffle code to ensure that all
valid shuffles up to maxshuff are saved.

(complib5e.c, complib7e.c, complib8.c)
Fix -m 9c/C core dump with -z -1.

(cal_cons.c, cal_consf.c)
Reverse 'I', 'D' with CIGAR string.

>>June 26, 2011
(comp_lib8.c, compacc2.c)

Added the ability to search a library produced/specified by a script.
Like the "-e expand_script.sh", searching against a library that
begins with a '!', e.g. '!library_script.sh', causes the
library_script.sh to be executed, producing a temporary file from
stdout, which is then scanned as the database.  As with expansion
files, all the standard library syntax can be included.  Thus, if
cat_db.sh contains the command 'echo /seqdb/swissprot.lseg', the
command:

  fasta36 query.aa '\!@cat_db.sh'

will cause cat_db.sh to produce a temporary file with the line
"swissprot.lseg"; the temporary file will be interpreted as an
indirect file of filenames; and swissprot.lseg will be searched.  Note
that in Unix systems, the '!' must be preceeded by a '\' as shown
above, so that it is not interpreted by the shell.

>>June 23,24 2011
(compacc2.c, comp_lib8.c, mysql_lib.c)
A new save_best2() function in compacc2.c has been designed to
simplify the logic involved in saving best scores, with the goal of
moving some of the save_best() calculations into individual threads.

mysql_lib.c has a new command, close_tables, that allows a script to
remove a table after it has been used. (It might make more sense to
add this to the extension script option.)

>>June 14, 2011 (released as fasta-36.3.5a June, 2011)
(comp_lib7e.c, comp_lib8.c, compacc2.c)
Fix a serious bug in next_sequence_p() that caused a portion of the library to
be missed when long sequences filled the sequence buffer before the
slots were filled.

Make certain that thread buffers are cleared when running an expansion
script.

Return an extra '\n' before the final summary for consistency with
earlier versions.

>>June 2, 2011	 (released as fasta-36.3.5 June, 2011)
(comp_lib8.c, comp_lib5e.c, comp_lib7e.c)
Fix a bug that indicated that linked expanded sequences were
pre-loaded for alignment when they were not.

>>May 24, 2011 (released as fasta-36.3.5)
(comp_lib8.c, comp_lib7e.c, comp_lib5e.c, mshowalign2.c, compacc2.c,
initfa.c, param.h, scaleswn.c)

The in-memory versions of the program are allocating much more memory
than they actually use, causing the memory limits to cut in too soon.
Fix this by using a smaller MAXLIB_P (36000) for searches against
protein libraries, and expanding/contracting the aa1b_size more
sensibly.  Also add lost_memK value to track lost memory.  For protein
searches, lost memory is now around 15% of allocated memory (down from
40%).

Numerous fixes to improve formatting of HTML output.  Full statistics
parameters are now available with the fdata output.

Add fset_vars() to comp_lib8.c to set m_msg.max_memK properly.
Parameters have been modified to ensure less memory waste (all buffers
have 1000 sequences); Drop default 64-bit library memory limit to 8GB
(-XM8G, LIB_MEMK=8G).

>>May 25, 2011
(comp_lib8.c, comp_lib7e.c, comp_lib5e.c, mshowbest.c)

Add the '-b >1' option, guarantees that at least 1 result is shown,
but otherwise limits by E()-value.  '-b =10' guarantees to show
exactly 10 results (never more or less if the library is large
enough), '-b 10' will show no more than 10 results, limited by -E
e_cut, and '-b >1' will show at least 1 result, but is otherwise
limited by -E e_cut.

>>May 19, 2011
(comp_lib8.c, compacc2.c, param.h)
comp_lib8.c is a version of comp_lib7e.c that keeps sequences in
memory over multiple searches, but returns seqr_chains of buffers of
sequences as they are read, rather than waiting for everything to be
read. comp_lib8.c will automatically allocate up to 2 GB (32-bit
machines) or 8 GB (64-bit machines) to hold the sequence database in
a multiple query search.  This number can be increased or decreased
using the -XM# (megabytes) or -XM#G (gigabytes) option, or by setting
the LIB_MEMK environment variable.  -XM4G (LIB_MEMK=4G) makes 4GB
available for sequence libraries; -XM-1 makes all machine memory
available.

>>May 5 2011
(mshowbest.c)
Fix problems that prevented "-b align_number" properly limit output
with "-z -1".  "-z -1" also broke multiple HSPs (since no threshold
could be calculated); fixed.
(dropnfa.c)
Fix some offset arithmetic that prevented FASTA alignments from
extending to full length in do_walign().

>>May 4, 2011
(scaleswn.c)
Provide additional checks for division by low numbers in fit_llen2()
and fit_llens().  The similarities between fit_llen(), fit_llens(),
and fit_llen2() have been highlighted, and their differences
documented.  scaleswn.c now provides pstat_info, which writes all the
values required to re-calculate zscores or E()-values from raw scores.

>>May 2, 2011
(dropnfa.c)
Fix a problem with the traditional cgap(join)/optcut(opt) thresholds
(no longer used by default) caused by allowing ktup=3 for proteins.
The ktup=3 modification increased the cgap/opt thresholds by 6.

(comp_lib5e.c, comp_lib7e.c, comp_lib8.c)
Confirm identity of -m # and -m "F3 file.out".  Small differences fixed.

(mshowbest.c, mshowalign2.c)
Remove gi|12345 information from -m B, -m BB blast-like output.  NCBI
Blast does not display gi numbers.

>>Apr. 22, 2011
(doinit.c, initfa.c)
Several of the less common options have been changed to expanded
options, changing the meaning of -X (which now specifies expanded
options), as well as -o, -1, -B, -x, and -y.  -o now provides the
offset coordinates previously specified with -X; -B is now -XB, -o
-Xo, -x -Xx1,-1, and -y -Xy, e.g. -Xy32.

>>Apr. 19, 2011
(comp_lib7e.c, comp_lib5e.c, doinit.c, mshowbest.c)
Test lastest version with -I interactive mode.  Modificiations
required to ensure that aligments goto outfd, not stdout, when
filename is entered.  In addition, in interactive mode there can be
more scores shown than e_cut, so bbp->repeat_thresh must be set in
showbest() not main() program.

>>Apr. 17, 2011
(comp_lib7e.c, doinit.c, compacc.c)

The FASTA programs now support multiple output files with different -m
out_fmt types using the -m "F# out_file" or -m "F#,#,# out_file"
option.  Normally, the -m out_fmt option applies to the default output
file, which is either stdout, or specified with -O out_file (or within
the program in interactive mode). With -m F, an output format can be
associated with a separate output file, which will contain a complete
FASTA program output.  Thus,

  ssearch36 -m 9c -m "FBB blast.out_file" -m "F10 m10.out_file" query library

Will sent the -m 9c output to stdout, but will also send -m BB output
to blast.out_file, and -m 10 output to m10.out_file.  Consistent -m
out_fmt comands can be set to the same file by separating them with
','; e.g.:

  ssearch36 -m 9c -m "F9c,10 m9c_10.out_file" query library.

Producing alternative format alignments in different files has little
additional computational cost.

One of the shortcomings of this approach is that it affects only the
output format, not the other options that modify the amount of output.
Thus, if you specify -E 0.001; that expect threshold will be used for
all the output files.  When a -m option can modify the output (e.g. -m
8 sets -d 0), that modification persists only for that file.

>>Apr. 14, 2011
(initfa.c)
Fix bugs in e_cut_r calculation that made it much too low for
lalign36, and used the >1.0 divisor improperly for all programs
(change from e_cut_r = e_cut_r/divisor to e_cut_r = e_cut/divisor).

>>Apr. 11, 2011
(comp_lib5e.c, comp_lib7e.c, compacc.c)

The non-preload version of FASTA (comp_lib5.c) has been extended to
allow script expansion (comp_lib5e.c). To do this, the central score
calculation loops have been moved to getlib_buf_work(), just as
seqr_chain_work() was created for comp_lib7e.c.  Moreover, the
function used to build the link_file names is build_link_data() is now
in compacc.c.  Differences between comp_lib5e.c and comp_lib7e.c have
been reduced.

>>Apr. 5, 2011
(comp_lib7e.c)
Fix issue with closing unopened link_lib_list_p when no results are
found. Remove no-sequence error message for link library file.

>>Apr. 1, 2011
(comp_lib7e.c)
The -e script.sh has been generalized to have all the capabilities of
a library file, in particular '@' specifies an indirect file, and
"script.sh #" allows a library type to be specified.  Thus, the
script.sh invoked by "@script.sh" should not produce a fasta file; it
should produce a file that contains the name of a fasta file (or
possibly some other format).  If '@' is used, the link_lib file
written to stdout will be prepended with '@', and treated as an
indirect file of file names.

(comp_lib5.c, comp_lib7.c, comp_lib7e.c)
Fix problem with null refstr (no Please cite:).

>>Mar. 31, 2011
(comp_lib7.c, comp_lib7e.c)
close_lib() was being called after each query.  This is incorrect for
versions (like comp_lib7) that keep the entire database in memory; the
files must be kept open to allow ranlib() to get long descriptions
(alternatively, a long description could be read initially).

(comp_lib5.c, comp_lib7.c, comp_lib7e.c)
Fix query offset coordinates for long queries that are broken up.
Allow query library to have zero-length sequences without stopping
(queries now stop when end-of-file is reached).

(upam.h)
Fix gap penalties for BLOSUM80 matrix (change from -14, -2 to -10, -2).

>>Mar. 29, 2011
(comp_lib7e.c, doinit.c)

Add the ability to search an expanded set of sequences based on the
accessions from the initial search using "-e expand.sh" option.
If "-e expand_script.sh" is specified, the command:

    expand.sh link_acc_file > link_lib_file

is run by the program (fasta36, ssearch36, fastx36, etc), where
link_acc_file and link_lib_file are temporary file names produced by
the program. (The location of the temporary files can be specified
with the $TMP_DIR environment variable.)  link_acc_file contains a
list of accession strings for the statistically significant hits - the
information in the description line to the first space, e.g.

gi|121719|sp|P08010|GSTM2_RAT
gi|121746|sp|P09211|GSTP1_HUMAN

from a search against my pir1.lseg library.

"expand.sh" then reads that file, extracts the accession information,
expands the accessions to a new set of accessions, extracts the
expanded set of accessions from a database and writes them to
standard output (which is saved in the temporary link_lib_file
name). The sequences in expanded link_lib_file are then added to the
initial search, and included in the list of best scores (and
alignments) if their scores are statistically significant. The
additional sequences do not change the initial library size.

To test the expansion capability, use an expand.sh script that simply
cat's a file of homologs to stdout (which will go to link_lib_file and
be read), e.g. expand.sh contains "cat ../seq/gst.lib".

Building a program that can take an arbitrary list of accessions and
produce a library of homologs is more complicated (and slower), but
will allow a smaller database to be searched yet produce results
similar to those found from a larger database.

>>Mar. 24, 2011		(released as fasta-36.3.4)
(comp_lib7.c, dropfx.c, dropfz2.c, doinit.c)
Fix a bug in the new help display; identify and correct various memory
leaks and references to uninitialized data.

>>Mar. 15, 2011
(doc/fasta3x.me, fasta3x.tex)
The ancient, rarely updated, fasta3x.me has been replaced with
fasta3x.tex, with the goal of producing a more up-to-date, accurate,
and comprehensive document describing the capabilities of the FASTA
programs.  In addition, fasta36.1 has been updated/corrected.

(make/Makefile.os_x86_64)
Mac OS X clang 2.0, distributed with Xcode4.0, does not properly
optimize the smith_waterman_sse2_word() in smith_waterman_sse2.c when
clang -O is used to compile.

>>Mar. 4, 2011
(doinit.c)
Histograms are now turned off by default.  -H shows histograms for all
programs, not just the *_mpi (PCOMPLIB) programs.

>>Feb. 27, 2011
(make/Makefile36m.common, Makefile.pcom_t, Makefile.pcom_s)

The threaded programs are now the default, and the *_t versions of
programs have been removed from the Unix and unix-like (MacOX)
distributions.  Windows versions can have either threaded or
non-threaded versions, since the threaded windows programs require an
additional library. Serial versions of the programs can still be built
by editing the make/Makefile36m.common file, and using
include Makefile.pcom_s instead of include Makefile.pcom_t.

The documentation has been edited to reflect these changes.

>>Feb. 24, 2011 (comp_lib5.c, comp_lib7.c, doinit.c, initfa.c,
structs.h) The FASTA programs have a much more informative help
system.  If the -DSHOW_HELP option is included in the Makefile, the
following changes occur: (1) the program is no longer interactive by
default. To get interaction, use the -I option (-I previously meant
showing the identity alignment in lalign; that option is now available
with -J). (2) fasta36 and fasta36 -h present a short help message. (3)
fasta36 -help provides a complete list of options with a more complete
set of options.  The getopt() option strings are now built
dynamically.

>>Feb. 18-21, 2011
(doinit.c)
Fix missing -m 9i percent identity/alignment length.  Fix issues with
short sequence description in -m 6 (html) mode.

>>Feb. 17, 2011
(comp_lib5.c, comp_lib7.c, doinit.c)
Implementation of -m BB which provides completely BLAST-like output
(not just alignments).

Modification of the -b ### option.  Previously, -b 100 guaranteed 100
alignments; now -b 100 limits to 100 alignments if more than 100
alignments have E()-values less than the -E threshold. An '=' symbol
before the number reverts to the previous behavior; e.g. -m =100
guarantees 100 alignments, regardless of E()-value (-m =100 is
equivalent to -m 100 -E 100000.0, and disables other setting of the
E()-value threshold).

>>Feb. 10, 2011
(doinit.c, mshowalign2.c, c_dispn.c)
The FASTA programs have a new alignment option, "-m B", which shows
alignments in BLAST format (no context, coordinates on the same line,
BLAST symbols for matches and mismatches.)  This version does not
change the descriptions of the alignments, which are still FASTA like,
but the alignments themselves should look just like BLAST alignments.
Option -m BB makes output even more blast-like, showing not only the
alignments, but the initial set of high scoring sequences, and other
initial information, like BLAST+.

>>Feb. 9, 2011 	released as fasta-36.3.3
(dropfs2.c, initfa.c, comp_lib*.c)
Modify fasts36/fastm36 to allow up to ktup=3 for proteins; ktup=6 for
DNA (previously the max was ktup=2 for both).

Modify version string to match release version number.

>>Feb. 6, 2011
(initfa.c)
Fix bug that prevented fastm36 from working properly with DNA queries.

>>Jan. 31, 2011
(pcomp_subs2.c, work_thr2.c)
Fixes to fasty36_mpi/tfastx36_mpi problem.  Only fasty needs pascii[]
for alignments, but it wasn't being sent to workers. Fixed.  The MPI
versions of the programs have now been tested much more thoroughly.

>>Jan. 29, 2011
(comp_lib5.c, comp_lib6.c, comp_lib7.c, work_thr2.c, initfa.c,
param.h, dropfs2.c, scaleswt.c, dropfx.c)

Translated DNA shuffles (tfastx36, tfasty36) now shuffle DNA as
codons.  (1) Modify param.h pstruct to include shuffle_dna3,
initialized in resetp() [initfa.c] (2) modify buf_shuf_work() to use
ppst-zs_win and ppst->shuffle_dna3. (3) Add ppst->zs_off=0 to
scaleswt.c/process_hist(). (4) Fix some memory leaks in dropfx.c.
(5) Fix some other memory leads in dropfs2.c.

>>Jan. 28, 2011
(initfa.c, scaleswn.c, mshowalign2.c)
Address crashes that occurred when novel scoring matrices and gap
penalties were specified, particularly for DNA.  Fix memory problem
with long (-L) sequence descriptions.

>>Jan. 23, 2011
(comp_lib7.c)
comp_lib7.c uses a more efficient strategy for reading chunks of
sequences that ensures that sequence data is contiguous for *_mpi
programs.  comp_lib7.c replaces comp_lib6.c, which will be removed.

>>Jan. 22, 2011
(many files)
Replace "mw.h" with "best_stats.h", a much more informative name.

(drop*.c, p_mw.h, w_mw.h)
Remove p_mw.h, w_mw.h from code base and update_params() from
drop*.c. These files are left over from the old p2_complib.c parallel
programs.

>>Jan. 21, 2011	released as fasta-36.3.2
(comp_lib5.c, comp_lib6.c, pcomp_subs2.c)
Fixes for MPI version of programs.  Earlier versions did not handle
DNA/translated DNA comparisons properly, because duplicated sequences
(forward/reverse strand) were not handled properly. The current code
produces the correct scores and alignments, but probably is much less
efficient than it should be.

>>Jan. 11, 2011
(initfa.c, scaleswn.c)
Re-enable DNALIB_LC (read lower-case DNA sequences as lower case).

Reset ktup to default after change for short query in multi-query
searches.

Address multiple issues associated with variable scoring matrices,
i.e. -s '?BP62'.  Introduce pst->pam_name for the actual scoring
matrix, to distinguish it from pst->pam_file, which can correspond to
the std_pam->abbrev, for values like BP62 (which encodes both a matrix
and a specific set of gap penalties).  Ensure that the new scoring
matrix is initialized and extended correctly.  Fix some issues with
scoring matrix names in scaleswn.c

>>Jan. 5, 2010
(dropnnw2.c, dropgsw2.h, global_sse2.c,h, glocal_sse2.c,h)
Include SSE2 optimization for global/global and global/local alignments
provided by Michael Farrar.  Global and glocal alignments are now 20X
faster.

>>Jan. 5, 2011	re-released as fasta-36.3.1
(initfa.c, last_tat.c)
Fix bug resetting pst.e_cut_r for DNA sequences.  Modify last_tat.c
code to use pre-loaded sequence if available. Remove last_tat.c
PCOMPLIB code.

>>Jan. 3, 2011	 released as fasta-36.3.1
(comp_lib5.c, comp_lib6.c)
Add >>><<<, >>>/// to -m 9,10 output for separating multiple query
searches.  Also clean up extra >>>query line before alignments when no
alignments are shown.

>>Dec. 16, 2010
(dropgsw2.c, dropnnw2.c, dropnsw.c, comp_lib5.c, comp_lib6.c)
Fix bug that caused ssearch to not invert coordinates for
reverse-complement DNA alignments (I never imagined using ssearch for
DNA) in dropgsw2.c, dropnnw2.c, and dropnsw.c.  Add SEQ_PAD to aa0[1]
(rev-comp copy) in comp_lib5.c, comp_lib6.c.

>>Dec. 14, 2010
Modify CIGAR strings for frameshifts, including 1F and 1R for forward
and reverse frameshifts.  Extensive documentation updates.
doc/fasta36.1 is the most comprehensive and accurate description of
FASTA options.

>>Dec. 1, 2010
(drop*.c, comp_lib5.c, comp_lib6.c)
Correct problems with copying for recursive sub-alignments.  Correct
bug in adler32_crc calculation that suggested a problem with continued
library sequences that did not exist.

(initfa.c, defs.h)
Use MAXLIB, rather than MAXLIB+MAXTST for comp_lib6.c, which
pre-allocates the sequence database.  Increase MAXLIB.

>>Nov. 24, 2010
(drop*.c, drop_func.h)
Modify drop*.c functions that do recursive sub-alignments to avoid
modifying the aa1[] sequence array, which conceivably could be in use
by other threads. do_walign() now has const *aa0 AND const *aa1.  To
prevent modification of aa1, sub-regions of aa1 are now copied into
newly allocated arrays.

>>Nov. 20, 2010
(cal_cons.c, mshowbest.c, mshowalign2.c, doinit.c)
The -m 9C option displays an alignment code in CIGAR format. (-m 9c
shows the older alignment encoding.)

>>Nov. 16, 2010		(beginning of fasta-36.3.*, verstr 36.07)
(initfa.c, apam.c, upam.h, param.h)

Provide the ability to adjust the scoring matrix based on the length
of the query sequence for alignments using a protein alphabet (this
could certainly be extended to DNA as well).  By including a '?'
before the scoring matrix, e.g. -s '?BP62', a shallower matrix will be
chosen if the entropy of the selected matrix (i.e. bit score per
aligned position) times the length of the protein query is
<=DEF_MIN_BITS (defs.h), currently 40 -- this value should be set
based on the library size).  The FASTA programs include BLOSUM50 (0.49
bits/pos) and BLOSUM62 (0.58 bits/pos) but can range to MD10 (3.44
bits/position). The variable scoring matrix option searches down the
list of scoring matrices to find one with information content high
enough to produce a 40 bit alignment score.  This option is included
primarily for metagenomics scans, which can include relatively short
DNA reads, and correspondingly short protein translations.

Also correct the short-query modification to ktup, so that it works
properly with translated FASTX/FASTY searches (ktup is set to 1 when
the query_length/3 <= 20).

(dropnfa.c, dropfx.c, dropfz2.c)
Shuffled sequence alignment scores are calculated identically to
library alignment scores. Previously, optimized scores were calculated
for all shuffled sequences for FASTA type alignments, even though
typically 20 - 40% of library sequences were optimized.  Now the two
sampling strategies are consistent, though this may cause problems
when only a small fraction of sequences are optimized.

Small changes to provide consistent dropnfa.c, dropfx.c, dropfz2.c
parameter display, and fix display with -m 10.

>>Nov. 15, 2010
(initfa.c)
Enable statistical thresholds by default (previously, they were
enabled with -c -1 or -c 0.01 or anything < 1.0).  The "classical"
join/opt threshold behavior can be restored with -c O (upper case
letter O), or by providing an optimization threshold >
1.0. Statistical thresholds dramatically speed up searches (typically
2-fold), and provide more accurate statistical estimates.  The old
join/optimization thresholds where optimized for BLOSUM50, and other
1/3-bit scaled scoring matrices, and did not work well with BLOSUM62.
Statistical thresholds have been tested extensively, particularly with
-z 21, and produce much more reliable statistical estimates.

>>Oct. 14, 2010
(Makefile.fcom, cal_cons.c)
Edits to re-enable compilation and successful execution of
tfasta36(_t). tfasta36 has been superceeded by tfastx36(_t), which is
faster, and treats frameshifts as a different type of gap.

>>Oct. 13, 2010
(mshowbest.c)
Make it more difficult to request more description/scores than are
available.

>>Sep. 30, 2010	 (released as fasta-36.2.7)
(comp_lib5.c, comp_lib6.c, dropnfa.c, dropfx.c, dropfz2.c)
Fix bugs in DEBUG versions with adler32_crc calculations on
overlapping sequences.  Add more informative error messages when
debugging.  Fix a problem with hist2.hist_a != NULL with some
compilers. Fix formats for some debugging error messages in dropnfa.c,
dropfx.c, and dropfz2.c.

Also fix repeat_threshold calculation for very short sequences, to
guarantee that all matches as good as the best match with the sequence
are found.  Fix some problems that prevented FASTA from finding short
repeats with short queries.

This version of the FASTA36 package offers an alternate main program
file, comp_lib6.c, which reads the entire database into memory before
doing the search.  Using comp_lib6.c can dramatically speed up
searches with multiple queries (there is no advantage with single
query sequences) on large multi-core computers, as each search is done
without re-reading the database.  On a 48-core processor, we see
speedups greater than 40X with ssearch36_t and fastx36_t.  To enable
comp_lib6.c, edit the make/Makefile36m.common file to comment out
lines refering to comp_lib5.c and un-comment lines referring to
comp_lib6.c.

>>Sep. 29, 2010
(comp_lib5.c, comp_lib6.c, mshowbest.c)
Added -m 8C option, which mimics BLAST+ tabular with comment lines
format.

>>Sep. 17, 2010
(dropfx.c)

Fix a bug in dropfx.c/do_walign() that modified library sequences.
(This only caused a problem with comp_lib6.c, which reads the entire
database into memory and re-uses sequence buffers.  Check sequence
consistency with adler32 CRC calculation.

>>Sep. 15, 2010
(mshowbest.c, mshowalign2.c)
Change the output format slightly.  E2() expect values (-z 21+) no
longer contain the library size (which is always the same as the
E(library_size) value), and the -m 9 +- line no longer contains the
frame information, since it is redundant. (The redundant rev-comp
remains on the >-- HSP lines.)

>>Sep. 14, 2010
(comp_lib5.c, mshowbest.c, drop*.c, cal_cons[f].c, etc.)
Implement BLAST -m 8 tabular output.

>>Sep. 9, 2010

(compacc.c) Fix a bug in pre_load_best() that disabled
-L long sequence descriptions.

(doinit.c) Fix a bug that prevented non-overlapping alignments from
being displayed when the -E threshold was changed.  Before -E 0.001
would disable additional alignments.  Now, -E "0.001 0" is required to
disable the additional alignments.

(drop*.c) The display of search parameters has changed to ensure that
gap penalties are displayed on the same line as the scoring
matrix. Previously, the FASTA "Parameters:" section looked like:

Parameters: BL50 matrix (15:-5)xS ktup: 2
 join: 42 (0.0944), opt: 30 (0.601), open/ext: -10/-2, width:  16
 Scan time:  0.450

With fasta-36.2.7 (and later), the Parameters: section is:

Parameters: BL50 matrix (15:-5), open/ext: -10/-2
 ktup: 2, join: 42 (0.102), opt: 30 (0.574), width:  16

The [T]FAST[X/Y] Parameters: section includes the frameshift/substitution penalties (tfasty36):

Parameters: BL50 matrix (15:-5) open/ext: -12/ -2 shift: -20, subs: -24
 ktup: 2, E-join: 0.5 (0.224), E-opt: 0.1 (0.0536),  width:  16

>>Aug. 3, 2010	(released as fasta-36.2.6)
(scaleswn.c)

Modifications to calc_thresh(), proc_hist_ml(), to better accommodate
search strategies (fast?? with statistical thresholds) that provide
complete scores only for a high-scoring fraction of sequences.  For
some query sequences, the E()-values from the database were sometimes
much "worse" than E2()-values, an observation that is
counter-intuitive (if parameters are estimated against shuffled
related sequences, the E()-values should get worse, not better).  For
some queries, the result was very dramatic (E() < 1E-80, E2() <
1E-150).  This error appears to occur because the z-trim or mle_cen
thresholds are including many related sequences.  -z 2 was modified to
censor more sequences when only a subset are scored, and -z 1 was
modified to adjust z-trim more carefully.  As a result, z-trim was
reduced, excluding more sequences.  If too many sequence are excluded,
then regression statistics do not work, and the program fails over to
Altschul-Gish statistics.

-z 21+ modified so that MLE statistics are used for shuffle E2()
values if Altschul-Gish statistics are used for the library
E()-values.

>>July 30, 2010
(comp_lib5.c, pcomp_subs2.c)

Fix bug in buf_align_seq() that allowed buffer over-runs with long DNA
sequences with MPI.  Checks on buffer over-runs are now included in
pcomp_subs2.c/put_rbuf(),get_wbuf().  Aug. 1, 2010, fixed similar bug
in buf_shuf_seq().  -z 21 now works with long DNA sequences.

>>July 28, 2010
(mshowalign2.c)
Fix lalign36/showalign() to show best sub-optimal E()-value, not
bptr[0] E()-value (often identical).

>>July 19, 2010	(released as fasta-36.2.5)
(wm_align.c, dropfx.c,dropfz2.c)
Fix some off-by-one boundary calculations to ensure that every query
that can fit into a library is aligned correctly.

>>May 18, 2010
Implement comp_lib5.c, which simplifies the structure of
comp_lib4.c by moving some calculations into functions.

>>May 10, 2010
Fix problem setting nshow with small library in interactive mode.

>>May 5, 2010  fasta-36.2.3
Fix bug that prevented shuffled scores to be used properly for small
databases (prss capability was lost).

>>May 2, 2010  fasta-36.2.2
Fix problem with tat_score values from fasts and fastm.  fasta35 did
not re-calculate the z-score after last_stats().  fasta36 does, so it
must ensure that the e-value (sometimes p-value) is used correctly.

>>Apr. 29, 2010
More extensive testing of the MPI-PCOMPLIB programs revealed some
problems sending sequences when (or more) frames for the same sequence
was used.  This problem has been addressed, and large scale testing of
fastx36_mpi (with 100K sequence queries in a run) works.

>>Apr. 16,19, 2010
(pcomp_subs2.c, comp_lib4.c, work_thr2.c)
The MPI-PCOMPLIB parallel version of the FASTA36 programs is
working. This PCOMPLIB version takes a very different approach from
the older PVM/MPI parallel programs (p2_complib2.c/p2_workcomp2.c) -
it works virtually identically to the threaded programs (sharing the
same work_thr2.c code and get_rbuf/put_rbuf() (manager) and
get_wbuf/put_wbuf() (worker/thread) functions.  As a result, in this
initial version, the database is NOT distributed to the nodes.  During
multiple searches, the library is re-read each time.  However, load is
distributed to workers exactly the way it would be for the threaded
system, so the workload should scale.

To distinguish them from the earlier mp35compsw, mp35compfa, etc, the
new versions are search36_mpi, fasta36_mpi, etc.

The programs work with multiple queries, and producing multiple
sub-alignments, and work with -m 9c encodings.

>>Apr. 7, 2010
(various Makefiles, comp_lib4.c, pcomp_subs2.c, thr_bufs2.h,
thr_buf_structs.h)

The MPI version of the threaded programs, sseach36_mp, now compiles.
pcomp_subs2.c replaces pthr_subs2.c, and thr_bufs.h ->
thr_buf_structs.h, thr.h -> thr_bufs2.h, and pcomp_bufs2.h has been
added as the equivalent of thr_bufs2.h for PCOMPLIB.

>>Apr. 2, 2010
(comp_lib4.c, work_thr2.c, compacc.c)
Implement init_aa0(), which isolates code that calls init_work and
sets up aa0s, aa1s, f_str[1] (reverse complement) and qf_str so that
the same code is used by the serial, threaded, and (future) PCOMP
versions.

(work_thr2.c)
work_thr2.c now contains code for either threaded or PCOMPLIB
processes. Threaded processes get stuff from work_info; PCOMPLIB
processes get the same information via messages sent from init_thr()
called by main().

>>Mar. 30, 2010
(comp_lib4.c, work_thr2.c, thr_bufs.c +pcomp_subs2.c

The the data buffers used to communicate between workers and threads
have been restructured to separate the old buf2_str, which contained
sequence, score results, and alignment results, into three buffers,
buf2_data_s, buf2_res_s, and buf2_ares_s, separating sequence data
from scores and alignments.  This was done to simplify communication
in the MPI/PVM environment. Workers should be able to return results
directly into the appropriate buffer.

>>Mar. 25, 2010		fasta-36.2.1

(dropfx.c, dropfz2.c)
Found/removed two "static" declarations in small_global that caused problems
with [t]fastx/y with threaded alignments.

>>Mar. 24, 2010  (now version 36.06 with threaded alignments)
(dropnfa.c)
The DNA band aligner in dropnfa.c was not thread safe.  This has been
fixed.

>>Mar. 23, 2010
Code for pre-loading/threaded-aligning sequences has been
significantly cleaned up.  Checks are made before RANLIB() and
re_getlib() in showbest() and showalign() that should be consistent
with annotations AND functions that cannot encode alignments.

Add mshowalign2.c (which does not do PCOMPLIB) to provide threaded
alignments.  build_ares_code() and buf_do_align() modified to ignore
MX_M9SUMM so that alignments are produced whenever demanded (still
does not do alignment if a_res is available).

>>Mar. 22, 2010
(comp_lib4.c, work_thr2.c, thr_bufs.h)

comp_lib4.c has been modified to thread the alignment encoding
(build_ares) for -m 9c. If m_msg.quiet and alignments are required for
showbest(), then the program identifies the number of alignments
required, reads the sequences (and annotations) into a buffer, and
sends them to the threads to be encoded.  Then, when showbest() is
called, bbp->have_ares has been set, and the alignments are not
re-calculated.  This should be extended to thread actual alignment
production, and additional work is required to clean-up the sequence
and bline(description) buffers before a second search.

>>Mar. 17, 2010
(comp_lib4.c, dropnfa,fx,fz2.c)
Modifications to provide more sensible E2() statistical estimates with
threshold-heuristic comparison functions and -z 21.  Also fixed bug
that caused the wrong zs_off to be used with -z 21. dropnfa,fx,fz2.c
now optimize all scores when shuff_flg is set.

>>Mar. 16, 2010
(comp_lib4.c, scaleswn.c, drop*.c)

A new, relatively consistent, statistical estimation strategy has been
introduced for the heuristic programs that optimize only a fraction of
scores (fasta36, [t]fast[xy]36).  Statistics-based heuristic
thresholds can increase search speed 2 - 4-fold by doing band
optimization on only a small fraction of library sequences (with the
-c -1 option, about 10% of alignments are band-optimized, compared
with more than 50% with the classic thresholds).  However, optimizing
only a small part of the library produces two classes of scores,
optimized (10% or less) and non-optimized, with different statistical
properties.  fasta36 addresses this problem by calculating statistical
estimates only for the optimized scores, and then correcting the
significance of the score by accounting for the frequency of
optimization.  For example, sampling only 5% of scores increases the
z-value (std. deviation above the mean) by -logE(0.05)*sqrt(6)/Pi =
2.34 which offsets the z-score by 23.4.  This effect is only seen when
the -c option is used to specify statistical thresholds, and is most
apparent when looking at the histogram, which will be offset by the
appropriate z-score.

This strategy appears to produce more accurate statistics in general,
but can produce less accurate statistics for the heuristic programs when
the -z 21 option is used.

>>Mar. 3, 2010

(comp_lib4.c)
Fix the new stats[] sampling strategy to sample >60K sequences more
more uniformly.  The old code massively over-sampled later sequences,
because of several bugs. The new code works as expected.  The first
60K sequences are represented about 30% more than the rest, but after
60K, sequences are sampled moderately uniformly.  The older
SAMP_STATS_MORE is uniform across all the scores.

(build_ares.c)
Move code to produce chains of alignments (a_res) produced by
do_walign, followed by subsequent calls to calc_id, calc_code, into a
new function, build_ares_code(), which is shared by the
serial/threaded and parallel (p2_workcomp.c) programs.  This is a
first step towards having the parallel programs produce multiple HSP
alignments.

>>Feb. 27, 2010

(lib_sel.c)
Fix problem with new chained library access that prevented more than
two files from being searched.  Also, library name string has been
lengthened to allow a list of libraries to be displayed.

>>Feb. 26, 2010

Parallel programs have been tested in both PVM and MPI versions, and
some additional bugs have been fixed.  Currently, the PVM/MPI versions
are fully functional, but only with FASTA35 capabilities.  The new
multiple HSP alignments and best-shuffle E2() scores are not yet
available.

>>Feb. 24, 2010

Fix some leaks, largely do to more complex alignment data structures
for multiple alignments.  Currently, all the major leaks are in data
structures allocated in main(), and which I don't bother to
de-allocate (mostly library buffer memory).

Change zsflag > 10 to zsflag >= 10 && zsflag < 20 in three places.
Too many shuffles were being done with zsflag==21.

>>Feb. 22, 2010

Begin conversion of p2_complib2.c/p2_workcomp.c.  Very old code to
allocate aln_d_base removed from v35 and v36. No code for best list
shuffle, or multiple high-scoring alignments.  However, the code now
works properly with statistical thresholds. (Changes made to
p2_complib2.c, p2_workcomp.c to update pst struct after last_param.()).

>>Feb. 19, 2010 fasta-36x6

Fix issues with -z 26 statistics.  Add description of E2() statistics.

Added option to specify statistics routine for best-shuffled
statistics independently of library statistics by specifying a second
-z option.  Thus, -z "21 2" uses regression scaled statistics for the
library estimate, and MLE statistics for the best-shuffled estimates.

>>Feb. 17, 2010	fasta-36x5

Some of the simplifications dealing with threads in comp_lib4.c failed
on some compilers and architectures. The code for terminating threads
has been modified to allow sequence buffers with zero entries, to
simplify the empty_buffer logic.  There is now an explicit option to
terminate threads by setting lib_bhead_p->stop_thread.  However, this
flag is never set, as rbuf_done() stops the threads instead.

Also fix problem with stats_idx being associated with wrong buf2_p in
two frame searches.

>>Feb. 15, 2010	fasta-36x4

fasta36 can now display both "search" (E()) and "shuffled" (E2())
E()-value calculation and display in the best scores and
alignments. If the -z option is greater than 20, then two evalues are
calculated, one from the search (e.g. -z 1 uses regression scaled
scores) and a second derived from shuffling the high scoring
sequences.  The high-scoring sequence shuffled scores are
approximately equivalent to doing a PRSS (pairwise shuffle), but more
efficient.  High-scoring shuffled E()-values (labled E2()) are
typically 2 - 5-fold more conservative for average composition
proteins, and 10 - 20X more conservative for biased composition
proteins.

Fix another bug in -S alignment scores vs opt scores in ssearch36 (see
Feb. 8).

>>February 12, 2010
(prev. version 142)

Create comp_lib4.c (from comp_lib3.c), which simplifies some of the
processes for handling buffers of results (no more empty_reader_bufs)
and enables shuffles of high-scoring sequences to evaluate significance.

>>February 8, 2010

Fix a problem with scores and E()-values for SSEARCH sub-alignments
when the -S option is used.  When the -S option was used to ignore
lower-case residues in query or library for the initial score, the
final alignments include the lower-case masked residues.  The
SSEARCH36 was using the non-masked alignment score, rather than the
orginal score (FASTA36, and [T]FAST[XY]36 used the masked score).
This was incorrect, as the statistics are calculated for masked
sequences.  The corrected version calculates both a non-masked and a
masked score, where the masked score (for subalignments) uses the
non-masked alignment.

[T]FAST[XY]36 had a related problem, which is that when multiple
sequences are in the query with the same pam2p[0] (no -S) score, then
the wrong alignment could be shown with the initial scores.  Fixing
this requires that the alignment routine only work on the region
specified from the initial band (fixed in dropnfa.c, dropfx.c, and
dropfz2.c).

>>February 4, 2010

The more efficient statistical thresholds in fasta36 have been
disabled by default.  They can be turned on with -c -1, or by setting
thesholds (-c "0.05 0.2" would set E_band_opt to 0.05 - target 5% of
sequences - and E_join at 20% target).

My initial implementation produced very inaccurate statistics,
presumably because only a small fraction of unrelated sequences were
being band-optimized (fasta35 typically optimized about 60% of library
sequences, fasta36 with statistical thresholds optimizes about 2%,
which causes a 2 - 3X speed increase). The sampling strategy for
fasta36, and [t]fast[xy]36 scores has been adjusted to provide
relatively accurate scores for searches that optimize only a small
fraction of sequences.  On the cases I have tested, statistical
accuracy is comparable to, or better than, the version 35 programs,
but probably not as robust as ssearch estimates.

>>January 29, 2010

The logic to predetermine where scores went for shuffling breaks when
some scores are not calculated (e.g. -M 200 - 300).  Fix by using
nstats as the index for nstats < MAX_STATS, and then use stats_idx
afterwards.

Provide more efficient score sampling logic.  The old method (left
over from fasta34 or earlier) generated a random number for every
sequence after MAX_STATS; if it was less than MAX_STATS, the sample
was used. This logic is still available with -DSAMP_STATS_MORE.  The
new logic samples every other sequence between MAX_STATS and
2*MAX_STATS, every third between 2*MAX_STATS and 3*MAXSTATS, etc, and
randomly replaces one of the stats scores.  For 430K SwissProt, this
reduces the number of samples from 178K to about 145K, and reduces the
number of calls to the random number generator from 430K to 85K.

>>January 28, 2010

(comp_lib3.c, mrandom.c) Tests of ssearch36 statistical accuracy
suggests that the default statistical estimates (-z 1) are not as
accurate as they should be with BLOSUM62, -11/-1.  Both -z 11 and -z 2
work better.  In FASTA35, -z 11 - 15 caused a 2X-slowdown (actually
more) because EVERY library sequence was shuffled, even though only a
fraction of the sequences (for libraries > 60,000 would be used for
the statistical calculation.  comp_lib3.c uses a more sophisticated
strategy for sampling scores after 60,000 so that sequences are only
shuffled and aligned if they will be used in the statistical
calculation.  Doing this on SwissProt, with 430,000 sequences, means
that ~180,000 additional shuffle alignments are done, not 430,000
additional.

However, using -z 11 with the threaded program was much more than
2X-slower -- random() is not re-entrant, and is designed to provide a
consistent set of random numbers over threads, so threads were waiting
on the random number generator, with a big performance penalty.  Using
code from WikiPedia, I implemented a random number generator
(mrandom.c) that saves a local copy of state, so threaded -z 11 has
the correct performance penalty.

>>January 25, 2010 (initfa.c 36.04 January 2010)

(dropfz2.c, aln_struct.h) At long last, tfasty36 correctly produces
multiple alignments on the reverse strand. (Jan. 26, 2010) Fixed
introduced bug in fasty36 that used wrong offset in recursion.

>>January 17, 2010

Extensive changes have been made to all the drop_* functions, so that
multiple alignment results are properly sorted from highest to lowest
sw_score. dropnfa.c, dropgsw2.c, dropfx.c and dropfz2.c now all use
similar strategies to calculate non-overlapping alternative alignments.
score_thresh thresholds are applied to rst.score[ppst->score_ix]
appropriately for all recursive functions.

>>August 24, 2009

Statistical thresholds have been adjusted to produce more
approximately the correct number of joins/band optimizations.  The
approximate fraction of joins/band optimizations is now shown in the
results.

>>August 21, 2009

fasta/fastx/fasty/tfastx/tfasty now use statistically based thresholds
for joining short segments and deciding to do a band optimization --
similar to the threshold strategy used by BLAST.

The statistical thresholds used are set with the
-c option, which used to be used to set optcut.  The -c option now has three ranges:

-c < 0       -- use the old FASTA thresholds, calculated in the same way
0 < -c < 1.0 --	use the statistical thresholds and set E_opt_cut.
c >= 1.0     -- use the old FASTA threshold, and specify it.

For 0 < -c < 1.0, a second argument can be supplied (-c "0.02 0.1")
for the joining E()-threshold.  If this value is < 1.0, it is used as
E_join; if it is > 1.0, E_opt_cut is multiplied by the value to get
E_join.

>>August 19, 2009

Implement Lambda/K/H based c_gap, opt_cut in dropnfa.c, dropfx.c
(fastx), and dropfz2.c (fasty).  Add ELK_to_s() to scaleswn.c.

>>August 11, 2009

Fix bug in dropfx.c that used the wrong variables for calculating
offsets into a long DNA sequence for subset alignments.

Stop putting sw_score in score[0] when no score[0] was calculated.
Use 0 instead.

>>July 31, 2009

(dropgsw2.c) Fix problems with dropgsw2.c that allowed poor
sub-alignments to be shown.  Consolidate merge_ares_acc() for all the
functions.  Add pst.do_rep to disable multiple alignments.

>>July 6, 2009

(initfa.c, apam.c, complib2.c, p2_complib.c) move changes for
validate_novel_aa() from fasta35.

(initfa.c) Enable checks for unusual characters ('Uu' in proteins) for
many more programs with the -p option.

>>June 16, 2009

Modify statistical sampling strategy to greatly simplify the
calculation.

>>May 15, 2009

Fix bug in lav2ps.c, lav2svg.c that occured when displaying very long
sequence alignments (e.g. genome alignments).  The maximum coordinate
is set properly now.

>>May 5, 2009

(initfa.c) Fix bug (int e_cut in pgm_def_arr[]) that prevented e_cut
to be set properly for lalign for DNA.

>>May 4, 2009

The functions that return multiple sub-alignments (HSPs) after the
best alignment have been modified to ensure that alignments are
returned sorted by score, by merging the list of alignments found to
the left and right of the best alignment.

>>April 28, 2009

(p2_complib2.c, p2_workcomp2.c, mshowbest.c, mshowalign.c) modified to
support new coordinate system, preliminary work on multiple HSPs in
parallel environment.

>>April 14, 2009

(comp_lib2.c, nmgetaa.c) Comprehensive restructuring of library file
list from a fixed length array to a variable length linked list.  The
link lists allows library files to insert additional files into the
list, so that, for example, a file of accession numbers can refer to a
list of files for the accessions.

Eventually, this should allow FASTA to support .pal/.nal files from
the NCBI, and to support files of file names most places file names
are allowed.

>>April 2, 2009		(from fasta35)

(structs.h, comp_lib2.c, doinit.c, mshowbest.c, mshowalign.c) The code
that selects the number of high scores to display has been reorganized
to support the -F e_low option (which was not implemented properly if
-b and -d were specified).  The code is simplified; m_msg.nshow is
used to specify the number of best scores listed, and min(m_msg.nshow,
m_msg.ashow) is used to specify the number of alignments shown.

>>March 26, 2009	(from fasta35 - fa35_04_07)

(initfa.c) Fix problems with 'U' recognition in DNA pam matrix,
correct implementation of -r +mat/-mis.  Previous versions of fasta35
may not have used the correct DNA matrix when the -r +mat/-mis option
was specified.

>>March 23, 2009	(initfa.c verstr -> 36.02)

(mshowbest.c, aln_structs.h) Add loop for displaying multiple aligned
regions with -m 9, -m 9i, and -m 9c in mshowbest.c.

>>March 22, 2009

(dropgsw2.c, dropnnw2.c, wm_align.c) Rearrange code in dropgsw2.c,
dropnnw2.c (which replaces dropnnw.c) so that a single function,
wm_align.c:nsw_malign() is responsible for recursive algnments for
both dropgsw2.c (sw_walign) and dropnnw2.c (nw_walign).  The strategy
for tnese (Smith-Waterman, Global-Local) alignments is
identical. nsw_malign() uses a function pointer that calculates S-W or
N-W that it gets from dropgsw2.c or dropnnw2.c

It might make sense to use a similar strategy for the recursive
translated alignments.

>>March 19, 2009

(map_db.c, mm_file.h) Fix another bug in map_db.c that appears for
sequence files larger than 2Gb.  MM_OFF is now consistently used in
more of the places where an int64_t might is required.

>>March 17, 2009

(list_db.c) Fix a bug in list_db that caused it to misread the maximum
sequence length, and then be off by 4-bytes for all the offsets.
Include list_db with map_db in the list of auxiliary programs.

>>Mar. 8, 2009		fa35_04_06

(comp_lib2.c, pthr_subs2.c, pthr_subs.h, doinit.c, dec_pthr_subs.c)
Dynamically allocate pthread_t *fa_threads, rather than limit it to
MAX_WORKERS.  MAX_WORKERS is no longer used in the Unix environment;
it gets its value from sysconf(_SC_NPROCESSORS_CONF).  If sysconf() is
not available, MAX_WORKERS is used.  The threaded programs should now
automatically adjust the number of threads to the number of
processors.  Moreover, the number of threads can be set to more than
the number of processors with -T #threads.  Also, max_workers was
renamed fa_max_workers, and pthread_t *threads is now *fa_threads.

>>Mar. 6, 2009

copied comp_lib2.c from v35 (fix for query offset coordinates)

>>Oct. 22, 2008

The programs that allow multiple alignments to be found include:

    ssearch36(_t)
    fasta36(_t)
    fastx36(_t)
    fasty36(_t)

fasts and fastf will probably not be updated in this way, because of
the difficulty in reconstructing alignments, but fastm may be.

Right now, the pvm/mpi versions of the programs do not support
multiple sub-alignments.

>>Sep. 25, 2008

Modify the syntax for the -E option to allow the repeat E()-value
cutoff to be specified in either of two ways.

       -E "e_cut e_rep"

If the value of e_rep is less than one, it is taken as the absolute
E()-value threshold for additional local domains, for example:

       -E "1.0 0.05" says use 1.0 for the main E()-value threshold,
        and 0.05 as the threshold for additional local alignments.

Alternatively, if e_rep >= 1.0, it is taken as a divisor for the
E()-value threshold, thus:

	-E "1.0 10.0"

Sets the E()-value threshold for additional local alignments to
1.0/10.0 = 0.1.

Finally, if e_rep <= 0.0, no multiple alignments are done (equivalent
to previous versions of FASTA).