1 /*  $Id: blast_stat.h 495576 2016-03-18 14:26:46Z rackerst $
2  * ===========================================================================
3  *
4  *                            PUBLIC DOMAIN NOTICE
5  *               National Center for Biotechnology Information
6  *
7  *  This software/database is a "United States Government Work" under the
8  *  terms of the United States Copyright Act.  It was written as part of
9  *  the author's official duties as a United States Government employee and
10  *  thus cannot be copyrighted.  This software/database is freely available
11  *  to the public for use. The National Library of Medicine and the U.S.
12  *  Government have not placed any restriction on its use or reproduction.
13  *
14  *  Although all reasonable efforts have been taken to ensure the accuracy
15  *  and reliability of the software and data, the NLM and the U.S.
16  *  Government do not and cannot warrant the performance or results that
17  *  may be obtained by using this software or data. The NLM and the U.S.
18  *  Government disclaim all warranties, express or implied, including
19  *  warranties of performance, merchantability or fitness for any particular
20  *  purpose.
21  *
22  *  Please cite the author in any work or product based on this material.
23  *
24  * ===========================================================================
25  *
26  * Author:  Tom Madden
27  *
28  */
29 
30 /** @file blast_stat.h
31  * Definitions and prototypes used by blast_stat.c to calculate BLAST
32  * statistics. @todo FIXME: needs doxygen comments
33  */
34 
35 #ifndef ALGO_BLAST_CORE__BLAST_STAT__H
36 #define ALGO_BLAST_CORE__BLAST_STAT__H
37 
38 #include <algo/blast/core/ncbi_std.h>
39 #include <algo/blast/core/blast_export.h>
40 #include <algo/blast/core/blast_program.h>
41 #include <algo/blast/core/blast_query_info.h>
42 #include <algo/blast/core/blast_message.h>
43 #include <util/tables/raw_scoremat.h>
44 
45 #ifdef __cplusplus
46 extern "C" {
47 #endif
48 
49 /**
50  * Defines for the matrix 'preferences' (as specified by S. Altschul).
51  * Used in arrays such as blosum45_prefs in blast_stat.c
52  */
53 #define BLAST_MATRIX_NOMINAL 0   /**< acceptable values, not recommended. */
54 #define BLAST_MATRIX_PREFERRED 1 /**< These value are preferred over others. */
55 #define BLAST_MATRIX_BEST 2      /**< This is the best value, only one per matrix. */
56 
57 
58 #define BLASTMAT_DIR "/usr/ncbi/blast/matrix" /**< Default location for blast databases. */
59 
60 /** callback to resolve the path to blast score matrices */
61 typedef char* (*GET_MATRIX_PATH) (const char*, Boolean);
62 
63 /**
64   Structure to hold the Karlin-Altschul parameters.
65 */
66 typedef struct Blast_KarlinBlk {
67       double   Lambda; /**< Lambda value used in statistics */
68       double   K; /**< K value used in statistics */
69       double   logK; /**< natural log of K value used in statistics */
70       double   H; /**< H value used in statistics */
71       double   paramC;  /**< for use in seed. */
72    } Blast_KarlinBlk;
73 
74 
75 /**
76   Tabulated results for faster erfc(x) lookup.
77   erfc(x) = 1/2 + 1/sqrt(2*pi) * \int_0^x { exp(-y^2/2)} dy
78   erfc(-\inf) = 0.0
79   erfc(+\inf) = 1.0
80   The erfc(x) is tabulated in p with step h, starting from a to b
81 */
82 typedef struct erfc_table {
83       double eps;
84       double a;
85       double b;
86       Int4   N;
87       double h;
88       double *p;
89    } erfc_table;
90 
91 /**
92   Structure to hold the Gumbel parameters (for FSC).
93 */
94 typedef struct Blast_GumbelBlk {
95       double  Lambda;    /**< the unscaled Lambda value */
96       double  C;
97       double  G;         /**< G is the total penalty for extension */
98       double  a;         /**< avg(L) = a     y + b    */
99       double  Alpha;     /**< var(L) = alpha y + beta */
100       double  Sigma;     /**< cov(L) = sigma y + tau  */
101       double  a_un;      /**< Ungapped a */
102       double  Alpha_un;  /**< Ungapped alpha */
103 
104       double  b;         /**< 2*G*(a_un - a) */
105       double  Beta;      /**< 2*G*(alpha_un - alpha) */
106       double  Tau;       /**< 2*G*(alpha_un - Sigma) */
107 
108       Int8 db_length;    /**< total length of database */
109 
110       Boolean filled;    /**< flag indicate the values of gbp are prepared */
111 
112    } Blast_GumbelBlk;
113 
114 
115 /********************************************************************
116 
117    Structures relating to scoring or the BlastScoreBlk
118 
119 ********************************************************************/
120 
121 #define BLAST_SCORE_MIN INT2_MIN   /**< minimum allowed score (for one letter comparison). */
122 #define BLAST_SCORE_MAX INT2_MAX   /**< maximum allowed score (for one letter comparison). */
123 
124 
125 /** Holds score frequencies used in calculation
126 of Karlin-Altschul parameters for an ungapped search.
127 */
128 typedef struct Blast_ScoreFreq {
129     Int4         score_min; /**< lowest allowed scores */
130     Int4         score_max; /**< highest allowed scores */
131     Int4         obs_min;   /**< lowest observed (actual) scores */
132     Int4         obs_max;   /**< highest observed (actual) scores */
133     double       score_avg; /**< average score, must be negative for local alignment. */
134     double*      sprob0;    /**< arrays for frequency of given score */
135     double*      sprob;     /**< arrays for frequency of given score, shifted down by score_min. */
136 } Blast_ScoreFreq;
137 
138 /** Scoring matrix used in BLAST */
139 typedef struct SBlastScoreMatrix {
140     int** data;         /**< actual scoring matrix data, stored in row-major
141                           form */
142     size_t ncols;       /**< number of columns */
143     size_t nrows;       /**< number of rows */
144     double* freqs;      /**< array of assumed matrix background frequencies -RMH-*/
145     double lambda;      /**< derived value of the matrix lambda -RMH- */
146 } SBlastScoreMatrix;
147 
148 /** Scoring matrix data used in PSI-BLAST */
149 typedef struct SPsiBlastScoreMatrix {
150     SBlastScoreMatrix* pssm;    /**< position-specific score matrix */
151     double** freq_ratios;       /**< PSSM's frequency ratios, dimensions are
152                                   specified in pssm data above */
153     Blast_KarlinBlk* kbp;       /**< Karlin-Altschul block associated with this
154                                   PSSM */
155 } SPsiBlastScoreMatrix;
156 
157 /** Allocates a new SPsiBlastScoreMatrix structure of dimensions ncols by
158  * BLASTAA_SIZE.
159  * @param ncols number of columns (i.e.: query length) [in]
160  * @return NULL in case of memory allocation failure, else new
161  * SPsiBlastScoreMatrix structure
162  */
163 NCBI_XBLAST_EXPORT
164 SPsiBlastScoreMatrix*
165 SPsiBlastScoreMatrixNew(size_t ncols);
166 
167 /** Deallocates a SPsiBlastScoreMatrix structure.
168  * @param matrix structure to deallocate [in]
169  * @return NULL
170  */
171 NCBI_XBLAST_EXPORT
172 SPsiBlastScoreMatrix*
173 SPsiBlastScoreMatrixFree(SPsiBlastScoreMatrix* matrix);
174 
175 /** Structure used for scoring calculations.
176 */
177 typedef struct BlastScoreBlk {
178    Boolean     protein_alphabet; /**< TRUE if alphabet_code is for a
179 protein alphabet (e.g., ncbistdaa etc.), FALSE for nt. alphabets. */
180    Uint1    alphabet_code; /**< NCBI alphabet code. */
181    Int2     alphabet_size;  /**< size of alphabet. */
182    Int2     alphabet_start;  /**< numerical value of 1st letter. */
183    char*    name;           /**< name of scoring matrix. */
184    ListNode*   comments;    /**< Comments about scoring matrix. */
185    SBlastScoreMatrix* matrix;   /**< scoring matrix data */
186    SPsiBlastScoreMatrix* psi_matrix;    /**< PSSM and associated data. If this
187                                          is not NULL, then the BLAST search is
188                                          position specific (i.e.: PSI-BLAST) */
189    Boolean  matrix_only_scoring;  /**< Score ungapped/gapped alignment only
190                                        using the matrix parameters and
191                                        with raw scores. Ignore
192                                        penalty/reward and do not report
193                                        Karlin-Altschul stats.  This is used
194                                        by the rmblastn program. -RMH- */
195    Boolean complexity_adjusted_scoring; /**< Use cross_match-like complexity
196                                            adjustment on raw scores. -RMH- */
197    Int4  loscore;   /**< Min.  substitution scores */
198    Int4  hiscore;   /**< Max. substitution scores */
199    Int4  penalty;   /**< penalty for mismatch in blastn. */
200    Int4  reward;    /**< reward for match in blastn. */
201         double  scale_factor; /**< multiplier for all cutoff and dropoff scores */
202    Boolean     read_in_matrix; /**< If TRUE, matrix is read in, otherwise
203                produce one from penalty and reward above. @todo should this be
204                 an allowed way of specifying the matrix to use? */
205    Blast_ScoreFreq** sfp;  /**< score frequencies for scoring matrix. */
206    /* kbp & kbp_gap are ptrs that should be set to kbp_std, kbp_psi, etc. */
207    Blast_KarlinBlk** kbp;  /**< Karlin-Altschul parameters. Actually just a placeholder. */
208    Blast_KarlinBlk** kbp_gap; /**< K-A parameters for gapped alignments.  Actually just a placeholder. */
209    Blast_GumbelBlk* gbp;  /**< Gumbel parameters for FSC. */
210    /* Below are the Karlin-Altschul parameters for non-position based ('std')
211    and position based ('psi') searches. */
212    Blast_KarlinBlk **kbp_std,  /**< K-A parameters for ungapped alignments */
213                     **kbp_psi,       /**< K-A parameters for position-based alignments. */
214                     **kbp_gap_std,  /**< K-A parameters for std (not position-based) alignments */
215                     **kbp_gap_psi;  /**< K-A parameters for psi alignments. */
216    Blast_KarlinBlk*  kbp_ideal;  /**< Ideal values (for query with average database composition). */
217    Int4 number_of_contexts;   /**< Used by sfp and kbp, how large are these*/
218    Uint1*   ambiguous_res; /**< Array of ambiguous res. (e.g, 'X', 'N')*/
219    Int2     ambig_size, /**< size of array above. FIXME: not needed here? */
220          ambig_occupy;  /**< How many occupied? */
221    Boolean  round_down; /**< Score must be rounded down to nearest even score if odd. */
222 } BlastScoreBlk;
223 
224 /** Scoring matrix data used for compressed protein alphabets */
225 typedef struct SCompressedAlphabet {
226     Int4  compressed_alphabet_size;  /**< letters in the compressed alphabet */
227     SBlastScoreMatrix* matrix;    /**< score matrix */
228     Uint1* compress_table;  /**< translation table (AA->compressed)*/
229 } SCompressedAlphabet;
230 
231 /** Deallocates SBlastScoreMatrix structure
232  * @param matrix structure to deallocate [in]
233  * @return NULL
234  */
235 NCBI_XBLAST_EXPORT
236 SBlastScoreMatrix*
237 SBlastScoreMatrixFree(SBlastScoreMatrix* matrix);
238 
239 /** Allocates a new SBlastScoreMatrix structure of the specified dimensions.
240  * @param ncols number of columns [in]
241  * @param nrows number of rows [in]
242  * @return NULL in case of memory allocation failure, else new
243  * SBlastScoreMatrix structure
244  */
245 NCBI_XBLAST_EXPORT
246 SBlastScoreMatrix*
247 SBlastScoreMatrixNew(size_t ncols, size_t nrows);
248 
249 /** Allocate a new compressed alphabet and score matrix
250  * @param sbp Current score matrix information [in]
251  * @param compressed_alphabet_size Desired size of compressed
252  *                  alphabet (current choices are limited to 10 or 15) [in]
253  * @param scale_factor Score matrix entries are scaled by this value [in]
254  * @return the new alphabet, or NULL on failure
255  */
256 NCBI_XBLAST_EXPORT
257 SCompressedAlphabet*
258 SCompressedAlphabetNew(BlastScoreBlk *sbp,
259                        Int4 compressed_alphabet_size,
260                        double scale_factor);
261 
262 /** Free a compressed alphabet and score matrix
263  * @param alphabet The compressed alphabet structure
264  * @return Always NULL
265  */
266 NCBI_XBLAST_EXPORT
267 SCompressedAlphabet*
268 SCompressedAlphabetFree(SCompressedAlphabet *alphabet);
269 
270 /**
271 Stores the letter frequency of a sequence or database.
272 */
273 typedef struct Blast_ResFreq {
274     Uint1   alphabet_code;    /**< indicates alphabet. */
275     double* prob;       /**< letter probs, (possible) non-zero offset. */
276     double* prob0;            /**< probs, zero offset. */
277 } Blast_ResFreq;
278 
279 /**
280  * Check that score blk is valid, returns zero if it is.
281  * @param sbp ScoreBlk to check [in]
282  * @return zero if valid
283 */
284 NCBI_XBLAST_EXPORT
285 int BlastScoreBlkCheck(BlastScoreBlk* sbp);
286 
287 /**
288  *   Allocates and initializes BlastScoreBlk
289  * @param alphabet either BLASTAA_SEQ_CODE or BLASTNA_SEQ_CODE [in]
290  * @param number_of_contexts how many strands or sequences [in]
291  * @return BlastScoreBlk*
292 */
293 NCBI_XBLAST_EXPORT
294 BlastScoreBlk* BlastScoreBlkNew (Uint1 alphabet, Int4 number_of_contexts);
295 
296 /** Deallocates BlastScoreBlk as well as all associated structures.
297  * @param sbp BlastScoreBlk to be deallocated [in]
298  * @return NULL pointer.
299  */
300 NCBI_XBLAST_EXPORT
301 BlastScoreBlk* BlastScoreBlkFree (BlastScoreBlk* sbp);
302 
303 /** Set the ambiguous residue (e.g, 'N', 'X') in the BlastScoreBlk*.
304  *  Convert from ncbieaa to sbp->alphabet_code (i.e., ncbistdaa) first.
305  *
306  * @param sbp the object to be modified [in|out]
307  * @param ambiguous_res the residue to be set on the BlastScoreBlk
308  * @return zero on success, others on error
309  */
310 NCBI_XBLAST_EXPORT
311 Int2 BLAST_ScoreSetAmbigRes (BlastScoreBlk* sbp, char ambiguous_res);
312 
313 
314 /** Calculate and fill the ungapped Karlin-Altschul parameters in the
315  * BlastScoreBlk structure (fields kbp_std, kbp_psi, and kbp of that structure).
316  * @param program BLAST program type, needed to decide whether to substitute
317  *                ideal values. [in]
318  * @param sbp Scoring block to work with [in] [out]
319  * @param query Buffer containing (concatenated) query sequence [in]
320  * @param query_info Information about offsets of concatenated queries [in]
321  * @param blast_message returns queries that could not be processed [out]
322  * @return 0 if ungapped Karlin-Altschul parameters could be calculated for
323  *        all of the query sequence's contexts; 1 if any of the contexts
324  *        failed (but all others will be populated).
325  */
326 NCBI_XBLAST_EXPORT
327 Int2
328 Blast_ScoreBlkKbpUngappedCalc(EBlastProgramType program,
329                               BlastScoreBlk* sbp, Uint1* query,
330                               const BlastQueryInfo* query_info,
331                               Blast_Message* *blast_message);
332 
333 /** This function fills in the BlastScoreBlk structure.
334  * Tasks are:
335  * -read in the matrix
336  * -set maxscore
337  * @param sbp Scoring block [in] [out]
338  * @param get_path pointer to function that will return path to matrix.  Only called
339  *  if built-in matrix not found [in]
340 */
341 NCBI_XBLAST_EXPORT
342 Int2 Blast_ScoreBlkMatrixFill (BlastScoreBlk* sbp, GET_MATRIX_PATH get_path);
343 
344 /** Callocs a Blast_KarlinBlk
345  * @return pointer to the Blast_KarlinBlk
346 */
347 NCBI_XBLAST_EXPORT
348 Blast_KarlinBlk* Blast_KarlinBlkNew (void);
349 
350 /** Copies contents of one Karlin block to another. Both must be allocated
351  * before this function is called.
352  * @param kbp_to Karlin block to copy values to [in] [out]
353  * @param kbp_from Karlin block to copy values from [in]
354  * @return 0 on success; -1 if either argument is NULL on input.
355  */
356 NCBI_XBLAST_EXPORT
357 Int2 Blast_KarlinBlkCopy(Blast_KarlinBlk* kbp_to, Blast_KarlinBlk* kbp_from);
358 
359 
360 /** Deallocates the KarlinBlk
361  * @param kbp KarlinBlk to be deallocated [in]
362  * @return NULL
363 */
364 NCBI_XBLAST_EXPORT
365 Blast_KarlinBlk* Blast_KarlinBlkFree(Blast_KarlinBlk* kbp);
366 
367 /** Fills in lambda, H, and K values, as calculated by Stephen Altschul
368  *  in Methods in Enzy. (vol 266, page 474).
369  * @param kbp object to be filled in [in|out]
370  * @param gap_open cost of gap existence [in]
371  * @param gap_extend cost to extend a gap one letter [in]
372  * @param matrix_name name of the matrix to be used [in]
373  * @param error_return filled in with error message if needed [out]
374  * @return zero on success
375  */
376 NCBI_XBLAST_EXPORT
377 Int2 Blast_KarlinBlkGappedCalc (Blast_KarlinBlk* kbp, Int4 gap_open,
378      Int4 gap_extend, const char* matrix_name, Blast_Message** error_return);
379 
380 /** Retrieves Karlin-Altschul parameters from precomputed tables, given the
381  * substitution and gap scores. Gap cost values greater than any of those
382  * listed in the tables ("greater" meaning that both values are greater than or
383  * equal, and at least one is strictly greater), are treated as infinite, and
384  * parameters values are copied from the ungapped Karlin block.
385  * @param kbp Allocated Karlin block to fill [in] [out]
386  * @param gap_open Gap openening (existence) cost [in]
387  * @param gap_extend Gap extension cost [in]
388  * @param reward Match reward score [in]
389  * @param penalty Mismatch penalty score [in]
390  * @param kbp_ungap Karlin block with ungapped Karlin-Altschul parameters [in]
391  * @param round_down specifies that the score should be rounded down to nearest even
392  *      score in some cases [in|out]
393  * @param error_return Pointer to error message. [in] [out]
394  */
395 NCBI_XBLAST_EXPORT
396 Int2
397 Blast_KarlinBlkNuclGappedCalc(Blast_KarlinBlk* kbp, Int4 gap_open,
398                               Int4 gap_extend, Int4 reward, Int4 penalty,
399                               Blast_KarlinBlk* kbp_ungap,
400                               Boolean* round_down,
401                               Blast_Message** error_return);
402 
403 
404 /** Calculates the Karlin-Altschul parameters assuming standard residue
405  * compositions for the query and subject sequences. It populates the kbp_ideal
406  * field of its sbp argument. This is used if the query is translated and the
407  * calculated (real) Karlin parameters are bad, as they're calculated for
408  * non-coding regions.
409  * @param sbp ScoreBlk used to calculate "ideal" values. [in|out]
410  * @return 0 on success, 1 on failure
411 */
412 NCBI_XBLAST_EXPORT
413 Int2 Blast_ScoreBlkKbpIdealCalc(BlastScoreBlk* sbp);
414 
415 /** Attempts to fill KarlinBlk for given gap opening, extensions etc.
416  *
417  * @param kbp object to be filled in [in|out]
418  * @param gap_open gap existence cost [in]
419  * @param gap_extend gap extension cost [in]
420  * @param matrix_name name of the matrix used [in]
421  * @param standard_only If true, include only the standard blosum and pam matrices [in]
422  * @return  -1 if matrix_name is NULL;
423  *          1 if matrix not found
424  *           2 if matrix found, but open, extend etc. values not supported.
425 */
426 NCBI_XBLAST_EXPORT
427 Int2 Blast_KarlinBlkGappedLoadFromTables(Blast_KarlinBlk* kbp, Int4 gap_open, Int4 gap_extend, const char* matrix_name, Boolean standard_only);
428 
429 /** Fills in gumbel parameters to estimate p-value using FSC
430  * @param gbp object to be filled in [in|out]
431  * @param gap_open cost of gap existence [in]
432  * @param gap_extend cost to extend a gap one letter [in]
433  * @param matrix_name name of the matrix to be used [in]
434  * @param error_return filled in with error message if needed [out]
435  * @return zero on success
436  */
437 NCBI_XBLAST_EXPORT
438 Int2 Blast_GumbelBlkCalc (Blast_GumbelBlk* gbp, Int4 gap_open,
439      Int4 gap_extend, const char* matrix_name, Blast_Message** error_return);
440 
441 /** Attempts to fill GumbelBlk for given gap opening, extensions etc.
442  *
443  * @param gbp object to be filled in [in|out]
444  * @param gap_open gap existence cost [in]
445  * @param gap_extend gap extension cost [in]
446  * @param matrix_name name of the matrix used [in]
447  * @return  -1 if matrix_name is NULL;
448  *          1 if matrix not found
449  *           2 if matrix found, but open, extend etc. values not supported.
450 */
451 NCBI_XBLAST_EXPORT
452 Int2 Blast_GumbelBlkLoadFromTables(Blast_GumbelBlk* gbp, Int4 gap_open,
453      Int4 gap_extend, const char* matrix_name);
454 
455 /** Prints a messages about the allowed matrices, BlastKarlinBlkGappedFill should return 1 before this is called.
456  * @param matrix the matrix to print a message about [in]
457  * @param standard_only, If true, include only the standad blosum and pam
458  * matrices [in]
459  * @return the message
460  */
461 NCBI_XBLAST_EXPORT
462 char* BLAST_PrintMatrixMessage(const char *matrix, Boolean standard_only);
463 
464 /** Prints a messages about the allowed open etc values for the given matrix,
465  * BlastKarlinBlkGappedFill should return 2 before this is called.
466  * @param matrix name of the matrix [in]
467  * @param gap_open gap existence cost [in]
468  * @param gap_extend cost to extend a gap by one [in]
469  * @return message
470  */
471 NCBI_XBLAST_EXPORT
472 char* BLAST_PrintAllowedValues(const char *matrix, Int4 gap_open, Int4 gap_extend);
473 
474 /** Calculates the parameter Lambda given an initial guess for its value */
475 NCBI_XBLAST_EXPORT
476 double
477 Blast_KarlinLambdaNR(Blast_ScoreFreq* sfp, double initialLambdaGuess);
478 
479 /** Calculates the Expect value based upon the search space and some Karlin-Altschul
480  * parameters.  It is "simple" as it does not use sum-statistics.
481  * @param S the score of the alignment. [in]
482  * @param kbp the Karlin-Altschul parameters. [in]
483  * @param searchsp total search space to be used [in]
484  * @return the expect value
485  */
486 NCBI_XBLAST_EXPORT
487 double BLAST_KarlinStoE_simple (Int4 S, Blast_KarlinBlk* kbp, Int8  searchsp);
488 
489 /** Calculates the Expect value based upon the Spouge's FSC method.
490  * @param S the score of the alignment. [in]
491  * @param gbp the Gumbel parameters. [in]
492  * @param qlen the query length. [in]
493  * @param slen the subject length. [in]
494  * @return the expect value
495  */
496 NCBI_XBLAST_EXPORT
497 double BLAST_SpougeStoE (Int4 S, Blast_KarlinBlk* kbp, Blast_GumbelBlk* gbp, Int4 qlen, Int4 slen);
498 
499 /** Estimate the score for a specified expect value.
500  * @param E the expect value of the alignment. [in]
501  * @param gbp the Gumbel parameters. [in]
502  * @param qlen the query length. [in]
503  * @param slen the subject length. [in]
504  * @return the score
505  */
506 NCBI_XBLAST_EXPORT
507 Int4 BLAST_SpougeEtoS (double E, Blast_KarlinBlk* kbp, Blast_GumbelBlk* gbp, Int4 qlen, Int4 slen);
508 
509 /** Convert a P-value to an E-value.
510  *
511  * P-values and E-values may either represent statistics of a database
512  * search or represent statistics on the two sequences being compared.
513  * If given a database P-value, this routine will return a database
514  * E-value; if given a pairwise P-value, it will return a pairwise
515  * E-value.
516  *
517  * In the context of a database search, the available P-value is often
518  * a pairwise P-value, whereas the desired E-value is a database
519  * E-value.  When this it the case, the value returned by this routine
520  * should be multiplied by the effective length of the database and
521  * divided by the effective length of the subject.
522  *
523  * @param p the P-value to be converted [in] @return the corresponding
524  * expect value.
525  */
526 NCBI_XBLAST_EXPORT double BLAST_KarlinPtoE(double p);
527 
528 /** Convert an E-value to a P-value.
529  *
530  * E-values and P-values may either represent statistics of a database
531  * search or represent statistics on the two sequences being compared.
532  * If given a database E-value, this routine will return a database
533  * P-value; if given a pairwise E-value, it will return a pairwise
534  * P-value.
535  *
536  * In the context of a database search, the available E-value is
537  * typically a database E-value, whereas the desired P-value is a
538  * pairwise P-value.  When this is the case, the E-value should be
539  * divided by the effective length of the database and multiplied by
540  * the effective length of the subject, before BLAST_KarlinEtoP is
541  * called.
542  *
543  * @param x the expect value to be converted [in]
544  * @return the corresponding p-value.
545  */
546 NCBI_XBLAST_EXPORT
547 double BLAST_KarlinEtoP(double x);
548 
549 /** Compute a divisor used to weight the evalue of a collection of
550  * "nsegs" distinct alignments.  These divisors are used to compensate
551  * for the effect of choosing the best among multiple collections of
552  * alignments.  See
553  *
554  * Stephen F. Altschul. Evaluating the statitical significance of
555  * multiple distinct local alignments. In Suhai, editior, Theoretical
556  * and Computational Methods in Genome Research, pages 1-14. Plenum
557  * Press, New York, 1997.
558  *
559  * The "decayrate" parameter of this routine is a value in the
560  * interval (0,1). Typical values of decayrate are .1 and .5.
561  * @param decayrate adjusts for (multiple) tests of number of HSP sum groups [in]
562  * @param nsegs the number of HSPs in the sum group [in]
563  * @return divisor used to compensate for multiple tests
564  */
565 NCBI_XBLAST_EXPORT
566 double BLAST_GapDecayDivisor(double decayrate, unsigned nsegs );
567 
568 /** Calculate the cutoff score from the expected number of HSPs or vice versa.
569  * @param S The calculated score [in] [out]
570  * @param E The calculated e-value [in] [out]
571  * @param kbp The Karlin-Altschul statistical parameters [in]
572  * @param searchsp The effective search space [in]
573  * @param dodecay Use gap decay feature? [in]
574  * @param gap_decay_rate Gap decay rate to use, if dodecay is set [in]
575  */
576 NCBI_XBLAST_EXPORT
577 Int2 BLAST_Cutoffs (Int4 *S, double* E, Blast_KarlinBlk* kbp,
578                     Int8 searchsp, Boolean dodecay, double gap_decay_rate);
579 
580 /** Calculates the e-value for alignments with "small" gaps (typically
581  *  under fifty residues/basepairs) following ideas of Stephen Altschul's.
582  * @param start_points the number of starting points permitted between
583  *    adjacent alignments; max_overlap + max_gap + 1 [in]
584  * @param num the number of distinct alignments in this collection [in]
585  * @param xsum the sum of the scores of these alignments each individually
586  *    normalized using an appropriate value of Lambda and logK [in]
587  * @param query_length effective len of the query seq [in]
588  * @param subject_length effective len of the subject seq [in]
589  * @param searchsp_eff effective size of the search space [in]
590  * @param weight_divisor a divisor used to weight the e-value
591  *    when multiple collections of alignments are being considered by
592  *    the calling routine [in]
593  * @return the expect value
594  */
595 NCBI_XBLAST_EXPORT
596 double BLAST_SmallGapSumE (Int4 start_points, Int2 num,  double xsum,
597                            Int4 query_length, Int4 subject_length,
598                            Int8 searchsp_eff, double weight_divisor);
599 
600 /** Calculates the e-value of a collection multiple distinct
601  *   alignments with asymmetric gaps between the alignments. The gaps
602  *   in one (protein) sequence are typically small (like in
603  *   BLAST_SmallGapSumE) gap an the gaps in the other (translated DNA)
604  *   sequence are possibly large (up to 4000 bp.)  This routine is used
605  *   for linking HSPs representing exons in the DNA sequence that are
606  *   separated by introns.
607  * @param query_start_points the number of starting points in
608  *     the query sequence permitted between adjacent alignments;
609  *     max_overlap + max_gap + 1. [in]
610  * @param subject_start_points  the number of starting points in
611  *     the subject sequence permitted between adjacent alignments [in]
612  * @param num number of distinct alignments in one collection [in]
613  * @param xsum the sum of the scores of these alignments each individually
614  *    normalized using an appropriate value of Lambda and logK [in]
615  * @param query_length effective length of query [in]
616  * @param subject_length effective length of subject [in]
617  * @param searchsp_eff effective size of the search space [in]
618  * @param weight_divisor  a divisor used to weight the e-value
619  *    when multiple collections of alignments are being considered by
620  *    the calling routine [in]
621  * @return sum expect value.
622  */
623 NCBI_XBLAST_EXPORT
624 double BLAST_UnevenGapSumE (Int4 query_start_points, Int4 subject_start_points,
625                             Int2 num, double xsum,
626                             Int4 query_length, Int4 subject_length,
627                             Int8 searchsp_eff, double weight_divisor);
628 
629 /** Calculates the e-value if a collection of distinct alignments with
630  *   arbitrarily large gaps between the alignments
631  * @param num number of distinct alignments in the collection [in]
632  * @param xsum the sum of the scores of these alignments each individually
633  *     normalized using an appropriate value of Lambda and logK [in]
634  * @param query_length effective length of query sequence [in]
635  * @param subject_length effective length of subject sequence [in]
636  * @param searchsp_eff effective size of the search space [in]
637  * @param weight_divisor  a divisor used to weight the e-value
638  *    when multiple collections of alignments are being considered by the
639  *    calling routine [in]
640  * @return sum expect value.
641  */
642 NCBI_XBLAST_EXPORT
643 double BLAST_LargeGapSumE (Int2 num,  double xsum,
644                            Int4 query_length, Int4 subject_length,
645                            Int8 searchsp_eff, double weight_divisor );
646 
647 /** Extract the recommended gap existence and extension values.
648  * Only to be used with protein matrices.
649  * @param  matrixName name of the matrix [in]
650  * @param gap_existence returns recommended existence cost [in|out]
651  * @param gap_extension returns recommended extension cost [in|out]
652  * @return zero on success
653  */
654 NCBI_XBLAST_EXPORT
655 Int2 BLAST_GetProteinGapExistenceExtendParams(const char* matrixName,
656                                        Int4* gap_existence,
657                                        Int4* gap_extension);
658 
659 /** Extract the recommended gap existence and extension values.
660  * Only to be used with blastn searches.
661  * @param reward match score [in]
662  * @param penalty mismatch score [in]
663  * @param gap_existence returns recommended existence cost [in|out]
664  * @param gap_extension returns recommended extension cost [in|out]
665  * @return zero on success
666  */
667 NCBI_XBLAST_EXPORT
668 Int2 BLAST_GetNucleotideGapExistenceExtendParams(Int4 reward,
669                                        Int4 penalty,
670                                        Int4* gap_existence,
671                                        Int4* gap_extension);
672 
673 /** Check the validity of the reward and penalty scores.
674  * Only to be used with blastn searches.
675  * @param reward match score [in]
676  * @param penalty mismatch score [in]
677  * @return TRUE on success
678  */
679 NCBI_XBLAST_EXPORT
680 Boolean BLAST_CheckRewardPenaltyScores(Int4 reward, Int4 penalty);
681 
682 /** Extract the alpha and beta settings for this matrixName, and these
683  *  gap open and gap extension costs
684  * @param matrixName name of the matrix used [in]
685  * @param alpha Karlin-Altschul parameter to be set [out]
686  * @param beta Karlin-Altschul parameter to be set [out]
687  * @param gapped TRUE if a gapped search [in]
688  * @param gap_open existence cost of a gap [in]
689  * @param gap_extend extension cost of a gap [in]
690  * @param kbp_ungapped Karlin block with ungapped values of the parameters [in]
691 */
692 NCBI_XBLAST_EXPORT
693 void BLAST_GetAlphaBeta (const char* matrixName, double *alpha,
694                          double *beta, Boolean gapped, Int4 gap_open,
695                          Int4 gap_extend, const Blast_KarlinBlk* kbp_ungapped);
696 
697 /** Extract the alpha and beta settings for these substitution and gap scores.
698  * If substitution or gap costs are not found in the tables, assume an ungapped
699  * search. Then alpha is computed using the formula Alpha = Lambda/H, and beta
700  * is equal to 0 except for some special cases.
701  * @param reward Match reward score [in]
702  * @param penalty Mismatch penalty score [in]
703  * @param gap_open Gap opening (existence) cost [in]
704  * @param gap_extend Gap extension cost [in]
705  * @param kbp Karlin block containing already computed Lambda, K and H
706  *            parameters.
707  * @param gapped_calculation Is this a gapped search? [in]
708  * @param alpha Alpha parameter for this scoring system [out]
709  * @param beta Beta parameter for this scoring system [out]
710  */
711 NCBI_XBLAST_EXPORT
712 Int2 Blast_GetNuclAlphaBeta(Int4 reward, Int4 penalty, Int4 gap_open,
713                             Int4 gap_extend, Blast_KarlinBlk* kbp,
714                             Boolean gapped_calculation,
715                             double *alpha, double *beta);
716 
717 /** Rescale the PSSM, using composition-based statistics, for use
718  *  with RPS BLAST. This function produces a PSSM for a single RPS DB
719  *  sequence (of size db_seq_length) and incorporates information from
720  *  the RPS blast query. Each individual database sequence must call this
721  *  function to retrieve its own PSSM. The matrix is returned (and must
722  *  be freed elsewhere). posMatrix is the portion of the complete
723  *  concatenated PSSM that is specific to this DB sequence
724  * @todo revise to use existing code
725  * @param scalingFactor used to rescale Lambda [in]
726  * @param rps_query_length length of query sequence [in]
727  * @param rps_query_seq the query sequence [in]
728  * @param db_seq_length Length of the database sequence [in]
729  * @param posMatrix matrix (actual) values to be used [in]
730  * @param sbp Structure with score matrix parameters [in][out]
731  * @return rescaled pssm
732  */
733 NCBI_XBLAST_EXPORT
734 Int4 ** RPSRescalePssm(double scalingFactor, Int4 rps_query_length,
735                    const Uint1 * rps_query_seq, Int4 db_seq_length,
736                    Int4 **posMatrix, BlastScoreBlk *sbp);
737 
738 
739 /**
740  * Computes the adjustment to the lengths of the query and database sequences
741  * that is used to compensate for edge effects when computing evalues.
742  *
743  * The length adjustment is an integer-valued approximation to the fixed
744  * point of the function
745  *
746  *    f(ell) = beta +
747  *               (alpha/lambda) * (log K + log((m - ell)*(n - N ell)))
748  *
749  * where m is the query length n is the length of the database and N is the
750  * number of sequences in the database. The values beta, alpha, lambda and
751  * K are statistical, Karlin-Altschul parameters.
752  *
753  * The value of the length adjustment computed by this routine, A,
754  * will always be an integer smaller than the fixed point of
755  * f(ell). Usually, it will be the largest such integer.  However, the
756  * computed length adjustment, A, will also be so small that
757  *
758  *    K * (m - A) * (n - N * A) > MAX(m,n).
759  *
760  * Moreover, an iterative method is used to compute A, and under
761  * unusual circumstances the iterative method may not converge.
762  *
763  * @param K      the statistical parameter K [in]
764  * @param logK   the natural logarithm of K [in]
765  * @param alpha_d_lambda    the ratio of the statistical parameters
766  *                          alpha and lambda (for ungapped alignments, the
767  *                          value 1/H should be used) [in]
768  * @param beta              the statistical parameter beta (for ungapped
769  *                          alignments, beta == 0) [in]
770  * @param query_length      the length of the query sequence [in]
771  * @param db_length         the length of the database [in]
772  * @param db_num_seqs       the number of sequences in the database [in]
773  * @param length_adjustment the computed value of the length adjustment [out]
774  *
775  * @return   0 if length_adjustment is known to be the largest integer less
776  *           than the fixed point of f(ell); 1 otherwise.
777  */
778 NCBI_XBLAST_EXPORT
779 Int4
780 BLAST_ComputeLengthAdjustment(double K,
781                               double logK,
782                               double alpha_d_lambda,
783                               double beta,
784                               Int4 query_length,
785                               Int8 db_length,
786                               Int4 db_num_seqs,
787                               Int4 * length_adjustment);
788 
789 
790 /** Allocates a new Blast_ResFreq structure and fills in the prob element
791     based upon the contents of sbp.
792  * @param sbp The BlastScoreBlk* used to init prob [in]
793 */
794 NCBI_XBLAST_EXPORT
795 Blast_ResFreq* Blast_ResFreqNew(const BlastScoreBlk* sbp);
796 
797 /** Deallocates Blast_ResFreq and prob0 element.
798  * @param rfp the Blast_ResFreq to be deallocated.
799 */
800 NCBI_XBLAST_EXPORT
801 Blast_ResFreq* Blast_ResFreqFree(Blast_ResFreq* rfp);
802 
803 
804 /** Calculates residues frequencies given a standard distribution.
805  * @param sbp the BlastScoreBlk provides information on alphabet.
806  * @param rfp the prob element on this Blast_ResFreq is used.
807  * @return zero on success
808 */
809 NCBI_XBLAST_EXPORT
810 Int2 Blast_ResFreqStdComp(const BlastScoreBlk* sbp, Blast_ResFreq* rfp);
811 
812 /** Creates a new structure to keep track of score frequencies for a scoring
813  * system.
814  * @param score_min Minimum score [in]
815  * @param score_max Maximum score [in]
816  * @return allocated and initialized pointer to Blast_ScoreFreq
817  */
818 NCBI_XBLAST_EXPORT
819 Blast_ScoreFreq*
820 Blast_ScoreFreqNew(Int4 score_min, Int4 score_max);
821 
822 /** Deallocates the score frequencies structure
823  * @param sfp the structure to deallocate [in]
824  * @return NULL
825  */
826 NCBI_XBLAST_EXPORT
827 Blast_ScoreFreq*
828 Blast_ScoreFreqFree(Blast_ScoreFreq* sfp);
829 
830 /** Fills a buffer with the 'standard' alphabet
831  * (given by STD_AMINO_ACID_FREQS[index].ch).
832  *
833  * @param alphabet_code specifies alphabet [in]
834  * @param residues buffer to be filled in [in|out]
835  * @param residue_size size of "residues" buffer [in]
836  * @return Number of residues in alphabet or negative returns upon error.
837  */
838 NCBI_XBLAST_EXPORT
839 Int2
840 Blast_GetStdAlphabet(Uint1 alphabet_code, Uint1* residues,
841                      Uint4 residue_size);
842 
843 /** Computes the parameters lambda, H K for use in calculating the
844  * statistical significance of high-scoring segments or subalignments (see
845  * comment on blast_stat.c for more details).
846  * @param kbp object containing Lambda, H, and K as well as scoring information [in|out]
847  * @param sfp array of probabilities for all scores [in]
848  * @return zero on success, 1 on error.
849  */
850 NCBI_XBLAST_EXPORT
851 Int2
852 Blast_KarlinBlkUngappedCalc(Blast_KarlinBlk* kbp, Blast_ScoreFreq* sfp);
853 
854 /**  Given a sequence of 'length' amino acid residues, compute the
855  *   probability of each residue and put that in the array resProb
856  *   Excludes ambiguity characters.
857  *
858  * @param sequence the sequence to be computed upon [in]
859  * @param length the length of the sequence [in]
860  * @param resProb the object to be filled in [in|out]
861  */
862 NCBI_XBLAST_EXPORT
863 void
864 Blast_FillResidueProbability(const Uint1* sequence, Int4 length, double * resProb);
865 
866 /** Fill in the matrix for blastn using the penaly and rewards
867  * The query sequence alphabet is blastna, the subject sequence
868  * is ncbi2na.  The alphabet blastna is defined in blast_stat.h
869  * and the first four elements of blastna are identical to ncbi2na.
870  * if sbp->matrix==NULL, it is allocated.
871  * @param sbp the BlastScoreBlk on which reward, penalty, and matrix will be set
872  [in|out]
873  * @return zero on success.
874 */
875 NCBI_XBLAST_EXPORT
876 Int2 BlastScoreBlkNuclMatrixCreate(BlastScoreBlk* sbp);
877 
878 /** Returns a pointer to the static compiled in version of the
879  * matrix.  If name is NULL or the matrix is not compiled in
880  * NULL is returned.
881  * @param name matrix name [in]
882  * @return pointer to matrix or NULL if not supported.
883  */
884 NCBI_XBLAST_EXPORT
885 SNCBIPackedScoreMatrix* BlastScoreBlkGetCompiledInMatrix(const char* name);
886 
887 #ifdef __cplusplus
888 }
889 #endif
890 #endif /* !ALGO_BLAST_CORE__BLAST_STAT__H */
891