File: VariantCaller.cpp

package info (click to toggle)
tvc 5.0.3%2Bgit20151221.80e144e%2Bdfsg-2
  • links: PTS, VCS
  • area: main
  • in suites: buster
  • size: 3,548 kB
  • sloc: cpp: 24,088; ansic: 3,933; python: 260; makefile: 16
file content (368 lines) | stat: -rw-r--r-- 12,528 bytes parent folder | download | duplicates (3)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
/* Copyright (C) 2012 Ion Torrent Systems, Inc. All Rights Reserved */

//! @file     VariantCaller.cpp
//! @ingroup  VariantCaller
//! @brief    HP Indel detection


#include <string>
#include <vector>
#include <stdio.h>
#include <pthread.h>
#include <armadillo>

#include "HypothesisEvaluator.h"
#include "ExtendParameters.h"

#include "InputStructures.h"
#include "HandleVariant.h"
#include "ReferenceReader.h"
#include "OrderedVCFWriter.h"
#include "BAMWalkerEngine.h"
#include "SampleManager.h"
#include "ExtendedReadInfo.h"
#include "TargetsManager.h"
#include "HotspotReader.h"
#include "MetricsManager.h"

#include "IonVersion.h"

using namespace std;


void TheSilenceOfTheArmadillos(ofstream &null_ostream)
{
  // Disable armadillo warning messages.
  arma::set_stream_err1(null_ostream);
  arma::set_stream_err2(null_ostream);
}

void * VariantCallerWorker(void *input);


int main(int argc, char* argv[])
{

  printf("tvc %s-%s (%s) - Torrent Variant Caller\n\n",
         IonVersion::GetVersion().c_str(), IonVersion::GetRelease().c_str(), IonVersion::GetGitHash().c_str());

  // stolen from "Analysis" to silence error messages from Armadillo library
  ofstream null_ostream("/dev/null"); // must stay live for entire scope, or crash when writing
  TheSilenceOfTheArmadillos(null_ostream);

  time_t start_time = time(NULL);


  ExtendParameters parameters(argc, argv);


  mkdir(parameters.outputDir.c_str(), S_IRWXU | S_IRWXG | S_IROTH | S_IXOTH);

  if (parameters.program_flow.rich_json_diagnostic || parameters.program_flow.minimal_diagnostic) {
    // make output directory "side effect bad"
    parameters.program_flow.json_plot_dir = parameters.outputDir + "/json_diagnostic/";
    mkdir(parameters.program_flow.json_plot_dir.c_str(), S_IRWXU | S_IRWXG | S_IROTH | S_IXOTH);
  }



  ReferenceReader ref_reader;
  ref_reader.Initialize(parameters.fasta);

  TargetsManager targets_manager;
  targets_manager.Initialize(ref_reader, parameters.targets, parameters.trim_ampliseq_primers);

  BAMWalkerEngine bam_walker;
  bam_walker.Initialize(ref_reader, targets_manager, parameters.bams, parameters.postprocessed_bam, parameters.prefixExclusion);
  bam_walker.GetProgramVersions(parameters.basecaller_version, parameters.tmap_version);

  SampleManager sample_manager;
  sample_manager.Initialize(bam_walker.GetBamHeader(), parameters.sampleName, parameters.force_sample_name);

  InputStructures global_context;
  global_context.Initialize(parameters, ref_reader, bam_walker.GetBamHeader());

  OrderedVCFWriter vcf_writer;
  vcf_writer.Initialize(parameters.outputDir + "/" + parameters.outputFile, parameters, sample_manager);

  OrderedBAMWriter bam_writer;

  HotspotReader hotspot_reader;
  hotspot_reader.Initialize(ref_reader, parameters.variantPriorsFile);

  // set up producer of variants
  AlleleParser candidate_generator(parameters, ref_reader, sample_manager, vcf_writer, hotspot_reader);

  MetricsManager metrics_manager;

  VariantCallerContext vc;
  vc.ref_reader = &ref_reader;
  vc.targets_manager = &targets_manager;
  vc.bam_walker = &bam_walker;
  vc.parameters = &parameters;
  vc.global_context = &global_context;
  vc.candidate_generator = &candidate_generator;
  vc.vcf_writer = &vcf_writer;
  vc.bam_writer = &bam_writer;
  vc.metrics_manager = &metrics_manager;
  pthread_mutex_init(&vc.candidate_generation_mutex, NULL);
  pthread_mutex_init(&vc.read_loading_mutex, NULL);
  pthread_mutex_init(&vc.bam_walker_mutex, NULL);
  pthread_mutex_init(&vc.read_removal_mutex, NULL);
  pthread_cond_init(&vc.memory_contention_cond, NULL);
  pthread_cond_init(&vc.alignment_tail_cond, NULL);

  vc.candidate_counter = 0;
  vc.dot_time = time(NULL) + 30;
  //vc.candidate_dot = 0;

  pthread_t worker_id[parameters.program_flow.nThreads];
  for (int worker = 0; worker < parameters.program_flow.nThreads; worker++)
    if (pthread_create(&worker_id[worker], NULL, VariantCallerWorker, &vc)) {
      printf("*Error* - problem starting thread\n");
      exit(-1);
    }

  for (int worker = 0; worker < parameters.program_flow.nThreads; worker++)
    pthread_join(worker_id[worker], NULL);

  pthread_mutex_destroy(&vc.candidate_generation_mutex);
  pthread_mutex_destroy(&vc.read_loading_mutex);
  pthread_mutex_destroy(&vc.bam_walker_mutex);
  pthread_mutex_destroy(&vc.read_removal_mutex);
  pthread_cond_destroy(&vc.memory_contention_cond);
  pthread_cond_destroy(&vc.alignment_tail_cond);


  Alignment* save_list = vc.bam_writer->process_new_etries(vc.bam_walker->alignments_first_);
  vc.bam_walker->SaveAlignments(save_list);
  save_list = vc.bam_writer->flush();
  vc.bam_walker->SaveAlignments(save_list);

  vcf_writer.Close();
  bam_walker.Close();
  metrics_manager.FinalizeAndSave(parameters.outputDir + "/tvc_metrics.json");

  cerr << endl;
  cout << endl;
  cout << "[tvc] Normal termination. Processing time: " << (time(NULL)-start_time) << " seconds." << endl;

  return 0;
}






void * VariantCallerWorker(void *input)
{
  VariantCallerContext& vc = *static_cast<VariantCallerContext*>(input);

  deque<VariantCandidate> variant_candidates;
  const static int kReadBatchSize = 40;
  Alignment * new_read[kReadBatchSize];
  bool success[kReadBatchSize];
  list<PositionInProgress>::iterator position_ticket;
  PersistingThreadObjects  thread_objects(*vc.global_context);
  bool more_positions = true;

  pthread_mutex_lock(&vc.bam_walker_mutex);
  MetricsAccumulator& metrics_accumulator = vc.metrics_manager->NewAccumulator();
  pthread_mutex_unlock(&vc.bam_walker_mutex);

  while (true /*more_positions*/) {

    // Opportunistic read removal

    if (vc.bam_walker->EligibleForReadRemoval()) {
      if (pthread_mutex_trylock(&vc.read_removal_mutex) == 0) {

        Alignment *removal_list = NULL;
        pthread_mutex_lock(&vc.bam_walker_mutex);
        vc.bam_walker->RequestReadRemovalTask(removal_list);
        pthread_mutex_unlock(&vc.bam_walker_mutex);
        //In rare case, the Eligible check pass, but another thread got to remove reads, then when this thread get the lock, it find there
        //is no reads to remove. The unexpected behavior of SaveAlignment() is that when NULL is passed in, it save all the reads and remove 
        // ZM tags. To prevent that, we need to check for empty.
        if (removal_list) {
          Alignment* save_list = vc.bam_writer->process_new_etries(removal_list);
          vc.bam_walker->SaveAlignments(save_list);
          pthread_mutex_lock(&vc.bam_walker_mutex);
          vc.bam_walker->FinishReadRemovalTask(save_list);
          pthread_mutex_unlock(&vc.bam_walker_mutex);
        }
        pthread_mutex_unlock(&vc.read_removal_mutex);

        pthread_cond_broadcast(&vc.memory_contention_cond);
      }
    }

    // If too many reads in memory and at least one candidate evaluator in progress, pause this thread
    // Wake up when the oldest candidate evaluator task is completed.

    pthread_mutex_lock(&vc.bam_walker_mutex);
    if (vc.bam_walker->MemoryContention()) {
      pthread_cond_wait (&vc.memory_contention_cond, &vc.bam_walker_mutex);
      pthread_mutex_unlock(&vc.bam_walker_mutex);
      continue;
    }
    pthread_mutex_unlock(&vc.bam_walker_mutex);


    //
    // Task dispatch: Decide whether to load more reads or to generate more variants
    //

    bool ready_for_next_position = false;
    if (vc.bam_walker->EligibleForGreedyRead()) {
      // Greedy reading allowed: if candidate generation in progress, just grab a new read
      if (pthread_mutex_trylock(&vc.candidate_generation_mutex) == 0) {
        pthread_mutex_lock(&vc.bam_walker_mutex);
        ready_for_next_position = vc.bam_walker->ReadyForNextPosition();
        if (not ready_for_next_position) {
          pthread_mutex_unlock(&vc.bam_walker_mutex);
          pthread_mutex_unlock(&vc.candidate_generation_mutex);
        }
      }

    } else {
      // Greedy reading disallowed: if candidate generation in progress,
      // wait for it to finish before deciding what to do.
      pthread_mutex_lock(&vc.candidate_generation_mutex);
      pthread_mutex_lock(&vc.bam_walker_mutex);
      ready_for_next_position = vc.bam_walker->ReadyForNextPosition();
      if (not ready_for_next_position) {
        pthread_mutex_unlock(&vc.bam_walker_mutex);
        pthread_mutex_unlock(&vc.candidate_generation_mutex);
      }
    }

    //
    // Dispatch outcome: Load and process more reads
    //

    if (not ready_for_next_position) {


      pthread_mutex_lock(&vc.read_loading_mutex);

      if (not vc.bam_walker->HasMoreAlignments()) {
        pthread_mutex_unlock(&vc.read_loading_mutex);
        pthread_cond_broadcast(&vc.memory_contention_cond);
        break;
      }

      pthread_mutex_lock(&vc.bam_walker_mutex);
      for (int i = 0; i < kReadBatchSize; ++i) {
        vc.bam_walker->RequestReadProcessingTask(new_read[i]);
        success[i] = false;
      }
      pthread_mutex_unlock(&vc.bam_walker_mutex);

      for (int i = 0; i < kReadBatchSize; ++i) {
        success[i] = vc.bam_walker->GetNextAlignmentCore(new_read[i]);
        if (not success[i])
          break;
      }
      pthread_mutex_unlock(&vc.read_loading_mutex);


      for (int i = 0; i < kReadBatchSize and success[i]; ++i) {
        vc.candidate_generator->BasicFilters(*new_read[i]);
        if (new_read[i]->filtered)
          continue;
        vc.targets_manager->TrimAmpliseqPrimers(new_read[i], vc.bam_walker->GetRecentUnmergedTarget());
        if (new_read[i]->filtered)
          continue;

        vc.candidate_generator->RegisterAlignment(*new_read[i]);
        UnpackOnLoad(new_read[i], *vc.global_context, *vc.parameters);
      }

      pthread_mutex_lock(&vc.bam_walker_mutex);
      for (int i = 0; i < kReadBatchSize; ++i)
        vc.bam_walker->FinishReadProcessingTask(new_read[i], success[i]);
      pthread_mutex_unlock(&vc.bam_walker_mutex);

      continue;
    }

    //
    // Dispatch outcome: Generate candidates at next position
    //


    if (not vc.bam_walker->HasMoreAlignments() and not more_positions) {
      pthread_mutex_unlock(&vc.bam_walker_mutex);
      pthread_mutex_unlock(&vc.candidate_generation_mutex);
      pthread_cond_broadcast(&vc.memory_contention_cond);
      break;
    }

    vc.bam_walker->BeginPositionProcessingTask(position_ticket);
    pthread_mutex_unlock(&vc.bam_walker_mutex);

    int haplotype_length = 1;
    vc.candidate_generator->GenerateCandidates(variant_candidates, position_ticket, haplotype_length);

    pthread_mutex_lock(&vc.bam_walker_mutex);
    int next_hotspot_chr = -1;
    long next_hotspot_position = -1;
    if (vc.candidate_generator->GetNextHotspotLocation(next_hotspot_chr, next_hotspot_position))
      more_positions = vc.bam_walker->AdvancePosition(haplotype_length, next_hotspot_chr, next_hotspot_position);
    else
      more_positions = vc.bam_walker->AdvancePosition(haplotype_length);
    pthread_mutex_unlock(&vc.bam_walker_mutex);

    if (not variant_candidates.empty()) {

      int vcf_writer_slot = vc.vcf_writer->ReserveSlot();
      vc.candidate_counter += variant_candidates.size();
      //while (vc.candidate_counter > vc.candidate_dot) {
      //  cerr << ".";
      //  /*
      //  pthread_mutex_lock(&vc.bam_walker_mutex);
      //  vc.bam_walker->PrintStatus();
      //  pthread_mutex_unlock(&vc.bam_walker_mutex);
      //  */
      //  vc.candidate_dot += 50;
      //}
      if (time(NULL) > vc.dot_time) {
        cerr << '.';
        vc.dot_time += 30;
      }

      pthread_mutex_unlock(&vc.candidate_generation_mutex);

      // separate queuing of variants from >actual work< of calling variants
      for (deque<VariantCandidate>::iterator v = variant_candidates.begin(); v != variant_candidates.end(); ++v) {
        EnsembleProcessOneVariant(thread_objects, vc, *v, *position_ticket);
        //v->isFiltered = true;
      }

      vc.vcf_writer->WriteSlot(vcf_writer_slot, variant_candidates);

      variant_candidates.clear();
    } else {
      pthread_mutex_unlock(&vc.candidate_generation_mutex);
    }

    metrics_accumulator.CollectMetrics(position_ticket, haplotype_length, vc.ref_reader);

    pthread_mutex_lock(&vc.bam_walker_mutex);
    bool signal_contention_removal = vc.bam_walker->IsEarlierstPositionProcessingTask(position_ticket);
    vc.bam_walker->FinishPositionProcessingTask(position_ticket);
    pthread_mutex_unlock(&vc.bam_walker_mutex);

    if (signal_contention_removal)
      pthread_cond_broadcast(&vc.memory_contention_cond);

  }
  return NULL;
}