1 /* The MIT License
2
3 Copyright (c) 2015 Adrian Tan <atks@umich.edu>
4
5 Permission is hereby granted, free of charge, to any person obtaining a copy
6 of this software and associated documentation files (the "Software"), to deal
7 in the Software without restriction, including without limitation the rights
8 to use, copy, modify, merge, publish, distribute, sublicense, and/or sell
9 copies of the Software, and to permit persons to whom the Software is
10 furnished to do so, subject to the following conditions:
11
12 The above copyright notice and this permission notice shall be included in
13 all copies or substantial portions of the Software.
14
15 THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR
16 IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,
17 FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE
18 AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER
19 LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM,
20 OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN
21 THE SOFTWARE.
22 */
23
24 #include "compute_features2.h"
25
26 namespace
27 {
28
29 class Igor : Program
30 {
31 public:
32
33 std::string version;
34
35 ///////////
36 //options//
37 ///////////
38 std::string input_vcf_file;
39 std::string output_vcf_file;
40 std::vector<GenomeInterval> intervals;
41 std::string interval_list;
42 std::string arg_sample_list;
43 char** samples;
44 int32_t *imap;
45 int32_t nsamples;
46 bool print_sites_only;
47
48 ///////
49 //i/o//
50 ///////
51 BCFOrderedReader *odr;
52 BCFOrderedWriter *odw;
53
54 //////////
55 //filter//
56 //////////
57 std::string fexp;
58 Filter filter;
59 bool filter_exists;
60
61 /////////
62 //stats//
63 /////////
64 int32_t no_samples;
65 int32_t no_variants;
66
67 /////////
68 //tools//
69 /////////
70 VariantManip *vm;
71
Igor(int argc,char ** argv)72 Igor(int argc, char ** argv)
73 {
74 version = "0.5";
75
76 //////////////////////////
77 //options initialization//
78 //////////////////////////
79 try
80 {
81 std::string desc = "Compute features for variants in vt pipeline from separate genotype files";
82
83 TCLAP::CmdLine cmd(desc, ' ', version);
84 VTOutput my;
85 cmd.setOutput(&my);
86 TCLAP::ValueArg<std::string> arg_intervals("i", "intervals", "Intervals", false, "", "str", cmd);
87 TCLAP::ValueArg<std::string> arg_interval_list("I", "interval-list", "File containing list of intervals", false, "", "file", cmd);
88 TCLAP::ValueArg<std::string> arg_fexp("f", "f", "filter expression []", false, "", "str", cmd);
89 TCLAP::ValueArg<std::string> arg_output_vcf_file("o", "o", "output VCF/VCF.GZ/BCF file [-]", false, "-", "str", cmd);
90 TCLAP::SwitchArg arg_print_sites_only("s", "s", "print site information only without genotypes [false]", cmd, false);
91 TCLAP::UnlabeledValueArg<std::string> arg_input_vcf_file("<in.vcf>", "input VCF file", true, "", "file", cmd);
92
93 cmd.parse(argc, argv);
94
95 input_vcf_file = arg_input_vcf_file.getValue();
96 output_vcf_file = arg_output_vcf_file.getValue();
97 parse_intervals(intervals, arg_interval_list.getValue(), arg_intervals.getValue());
98 print_sites_only = arg_print_sites_only.getValue();
99 fexp = arg_fexp.getValue();
100 }
101 catch (TCLAP::ArgException &e)
102 {
103 std::cerr << "error: " << e.error() << " for arg " << e.argId() << "\n";
104 abort();
105 }
106 };
107
initialize()108 void initialize()
109 {
110 //convert to paste like set up
111
112 //////////////////////
113 //i/o initialization//
114 //////////////////////
115 odr = new BCFOrderedReader(input_vcf_file, intervals);
116 odw = new BCFOrderedWriter(output_vcf_file);
117 if (print_sites_only)
118 {
119 odw->link_hdr(bcf_hdr_subset(odr->hdr, 0, 0, 0));
120 }
121 else
122 {
123 odw->link_hdr(odr->hdr);
124 }
125
126 bcf_hdr_append(odw->hdr, "##INFO=<ID=AC,Number=A,Type=Integer,Description=\"Alternate Allele Counts\">\n");
127 bcf_hdr_append(odw->hdr, "##INFO=<ID=AN,Number=1,Type=Integer,Description=\"Total Number Allele Counts\">\n");
128 bcf_hdr_append(odw->hdr, "##INFO=<ID=NS,Number=1,Type=Integer,Description=\"Number of Samples With Data\">\n");
129 bcf_hdr_append(odw->hdr, "##INFO=<ID=AF,Number=A,Type=Float,Description=\"Alternate Allele Frequency\">\n");
130 bcf_hdr_append(odw->hdr, "##INFO=<ID=GC,Number=G,Type=Integer,Description=\"Genotype Counts\">\n");
131 bcf_hdr_append(odw->hdr, "##INFO=<ID=GN,Number=1,Type=Integer,Description=\"Total Number of Genotypes Counts\">\n");
132 bcf_hdr_append(odw->hdr, "##INFO=<ID=GF,Number=G,Type=Float,Description=\"Genotype Frequency\">\n");
133
134 bcf_hdr_append(odw->hdr, "##INFO=<ID=HWEAF,Number=A,Type=Float,Description=\"Genotype likelihood based MLE Allele Frequency assuming HWE\">\n");
135 bcf_hdr_append(odw->hdr, "##INFO=<ID=HWEGF,Number=G,Type=Float,Description=\"Genotype likelihood based MLE Genotype Frequency assuming HWE\">\n");
136 bcf_hdr_append(odw->hdr, "##INFO=<ID=MLEAF,Number=A,Type=Float,Description=\"Genotype likelihood based MLE Allele Frequency\">\n");
137 bcf_hdr_append(odw->hdr, "##INFO=<ID=MLEGF,Number=G,Type=Float,Description=\"Genotype likelihood based MLE Genotype Frequency\">\n");
138 bcf_hdr_append(odw->hdr, "##INFO=<ID=HWE_LLR,Number=1,Type=Float,Description=\"Genotype likelihood based Hardy Weinberg ln(Likelihood Ratio)\">\n");
139 bcf_hdr_append(odw->hdr, "##INFO=<ID=HWE_LPVAL,Number=1,Type=Float,Description=\"Genotype likelihood based Hardy Weinberg Likelihood Ratio Test Statistic ln(p-value)\">\n");
140 bcf_hdr_append(odw->hdr, "##INFO=<ID=HWE_DF,Number=1,Type=Integer,Description=\"Degrees of freedom for Genotype likelihood based Hardy Weinberg Likelihood Ratio Test Statistic\">\n");
141 bcf_hdr_append(odw->hdr, "##INFO=<ID=FIC,Number=1,Type=Float,Description=\"Genotype likelihood based Inbreeding Coefficient\">\n");
142 bcf_hdr_append(odw->hdr, "##INFO=<ID=AB,Number=1,Type=Float,Description=\"Genotype likelihood based Allele Balance\">\n");
143
144 /////////////////////////
145 //filter initialization//
146 /////////////////////////
147 filter.parse(fexp.c_str());
148 filter_exists = fexp=="" ? false : true;
149
150 ////////////////////////
151 //stats initialization//
152 ////////////////////////
153 no_samples = bcf_hdr_nsamples(odr->hdr);
154 no_variants = 0;
155
156 if (!no_samples)
157 {
158 fprintf(stderr, "[%s:%d %s] No samples in VCF file: %s\n", __FILE__, __LINE__, __FUNCTION__, input_vcf_file.c_str());
159 exit(1);
160 }
161
162 ///////////////////////
163 //tool initialization//
164 ///////////////////////
165 vm = new VariantManip("");
166 }
167
compute_features()168 void compute_features()
169 {
170 bcf1_t *v = odw->get_bcf1_from_pool();
171 bcf_hdr_t *h = odr->hdr;
172 Variant variant;
173
174 int32_t *gts = NULL;
175 int32_t *pls = NULL;
176 int32_t *dps = NULL;
177 int32_t n_gts = 0;
178 int32_t n_pls = 0;
179 int32_t n_dps = 0;
180
181 odw->write_hdr();
182
183 while(odr->read(v))
184 {
185 variant.clear();
186 bool printed = false;
187
188 vm->classify_variant(h, v, variant);
189 if (filter_exists && !filter.apply(h,v,&variant))
190 {
191 continue;
192 }
193
194 bcf_unpack(v, BCF_UN_ALL);
195 int32_t ploidy = bcf_get_genotypes(odr->hdr, v, >s, &n_gts);
196 ploidy /= no_samples;
197
198 if (!n_gts)
199 {
200 continue;
201 }
202
203 bcf_get_format_int32(odr->hdr, v, "PL", &pls, &n_pls);
204 int32_t no_alleles = bcf_get_n_allele(v);
205
206 if (!n_pls)
207 {
208 continue;
209 }
210
211 float qual = 0;
212 int32_t n = 0;
213 Estimator::compute_qual(pls, no_samples, ploidy, no_alleles, qual, n);
214 if (n)
215 {
216 bcf_set_qual(v, qual);
217 }
218
219 int32_t g[ploidy];
220 for (int32_t i=0; i<ploidy; ++i) g[i]=0;
221 int32_t AC[no_alleles];
222 float AF[no_alleles];
223 for (int32_t i=0; i<no_alleles; ++i) AC[i]=0;
224 int32_t AN=0;
225 int32_t NS=0;
226 int32_t no_genotypes = bcf_an2gn(no_alleles);
227 int32_t GC[no_genotypes];
228 int32_t GN=0;
229 float GF[no_genotypes];
230
231 Estimator::compute_af(gts, no_samples, ploidy, no_alleles, AC, AN, AF, GC, GN, GF, NS);
232
233 if (NS)
234 {
235 int32_t* AC_PTR = &AC[1];
236 bcf_update_info_int32(odw->hdr, v, "AC", AC_PTR, no_alleles-1);
237 bcf_update_info_int32(odw->hdr, v, "AN", &AN, 1);
238 float* AF_PTR = &AF[1];
239 bcf_update_info_float(odw->hdr, v, "AF", AF_PTR, no_alleles-1);
240 if (GN)
241 {
242 bcf_update_info_int32(odw->hdr, v, "GC", GC, no_genotypes);
243 bcf_update_info_int32(odw->hdr, v, "GN", &GN, 1);
244 bcf_update_info_float(odw->hdr, v, "GF", GF, no_genotypes);
245 }
246 bcf_update_info_int32(odw->hdr, v, "NS", &NS, 1);
247 }
248
249 float MLE_HWE_AF[no_alleles];
250 float MLE_HWE_GF[no_genotypes];
251 n = 0;
252 Estimator::compute_gl_af_hwe(pls, no_samples, ploidy,no_alleles, MLE_HWE_AF, MLE_HWE_GF, n, 1e-20);
253 if (n)
254 {
255 float* MLE_HWE_AF_PTR = &MLE_HWE_AF[1];
256 bcf_update_info_float(odw->hdr, v, "HWEAF", MLE_HWE_AF_PTR, no_alleles-1);
257 bcf_update_info_float(odw->hdr, v, "HWEGF", &MLE_HWE_GF, no_genotypes);
258 }
259
260 float MLE_AF[no_alleles];
261 float MLE_GF[no_genotypes];
262 n = 0;
263 Estimator::compute_gl_af(pls, no_samples, ploidy,no_alleles, MLE_AF, MLE_GF, n, 1e-20);
264 if (n)
265 {
266 float* MLE_AF_PTR = &MLE_AF[1];
267 bcf_update_info_float(odw->hdr, v, "MLEAF", MLE_AF_PTR, no_alleles-1);
268 bcf_update_info_float(odw->hdr, v, "MLEGF", &MLE_GF, no_genotypes);
269 }
270
271 float lrts;
272 float logp;
273 int32_t df;
274 n = 0;
275 Estimator::compute_hwe_lrt(pls, no_samples, ploidy,
276 no_alleles, MLE_HWE_GF, MLE_GF, n,
277 lrts, logp, df);
278 if (n)
279 {
280 bcf_update_info_float(odw->hdr, v, "HWE_LLR", &lrts, 1);
281 bcf_update_info_float(odw->hdr, v, "HWE_LPVAL", &logp, 1);
282 bcf_update_info_int32(odw->hdr, v, "HWE_DF", &df, 1);
283 }
284
285 float f;
286 n = 0;
287 Estimator::compute_gl_fic(pls, no_samples, ploidy,
288 MLE_HWE_AF, no_alleles, MLE_GF,
289 f, n);
290 if (n)
291 {
292 bcf_update_info_float(odw->hdr, v, "FIC", &f, 1);
293 }
294
295 bcf_get_format_int32(odr->hdr, v, "DP", &dps, &n_dps);
296 if (n_dps)
297 {
298 float ab;
299 n = 0;
300 Estimator::compute_gl_ab(pls, no_samples, ploidy,
301 dps, MLE_GF, no_alleles,
302 ab, n);
303
304 if (n)
305 {
306 bcf_update_info_float(odw->hdr, v, "AB", &ab, 1);
307 }
308 }
309
310 if (print_sites_only)
311 {
312 bcf_subset(odw->hdr, v, 0, 0);
313 }
314
315 odw->write(v);
316 ++no_variants;
317 }
318
319 if(n_gts) free(gts);
320 if(n_pls) free(pls);
321 if(n_dps) free(dps);
322
323 odw->close();
324 };
325
print_options()326 void print_options()
327 {
328 std::clog << "compute_features v" << version << "\n";
329 std::clog << "\n";
330 std::clog << "Options: input VCF File " << input_vcf_file << "\n";
331 print_str_op(" [f] filter ", fexp);
332 print_int_op(" [i] Intervals ", intervals);
333 std::clog << "\n";
334 }
335
print_stats()336 void print_stats()
337 {
338 std::clog << "\n";
339 std::clog << "stats: variants : " << no_variants << "\n";
340 std::clog << "\n";
341 };
342
~Igor()343 ~Igor()
344 {
345 };
346
347 private:
348 };
349
350 }
351
compute_features2(int argc,char ** argv)352 void compute_features2(int argc, char ** argv)
353 {
354 Igor igor(argc, argv);
355 igor.print_options();
356 igor.initialize();
357 igor.compute_features();
358 igor.print_stats();
359 }
360
361