SingleQModel.h

   1 #ifndef SINGLEQMODEL_H_
   2 #define SINGLEQMODEL_H_
   3
   4 #include<cmath>
   5 #include<cstdio>
   6 #include<cassert>
   7 #include<cstring>
   8 #include<string>
   9 #include<algorithm>
  10 #include<sstream>
  11
  12 #include "utils.h"
  13 #include "my_assert.h"
  14 #include "Orientation.h"
  15 #include "LenDist.h"
  16 #include "RSPD.h"
  17 #include "QualDist.h"
  18 #include "QProfile.h"
  19 #include "NoiseQProfile.h"
  20
  21 #include "ModelParams.h"
  22 #include "RefSeq.h"
  23 #include "Refs.h"
  24 #include "SingleReadQ.h"
  25 #include "SingleHit.h"
  26 #include "ReadReader.h"
  27
  28 #include "simul.h"
  29
  30 class SingleQModel {
  31 public:
  32         SingleQModel(Refs* refs = NULL) {
  33                 this->refs = refs;
  34                 M = (refs != NULL ? refs->getM() : 0);
  35                 memset(N, 0, sizeof(N));
  36                 estRSPD = false;
  37                 needCalcConPrb = true;
  38
  39                 ori = new Orientation();
  40                 gld = new LenDist();
  41                 mld = NULL;
  42                 rspd = new RSPD(estRSPD);
  43                 qd = new QualDist();
  44                 qpro = new QProfile();
  45                 nqpro = new NoiseQProfile();
  46
  47                 mean = -1.0; sd = 0.0;
  48                 mw = NULL;
  49
  50                 seedLen = 0;
  51         }
  52
  53         //If it is not a master node, only init & update can be used!
  54         SingleQModel(ModelParams& params, bool isMaster = true) {
  55                 M = params.M;
  56                 memcpy(N, params.N, sizeof(params.N));
  57                 refs = params.refs;
  58                 estRSPD = params.estRSPD;
  59                 mean = params.mean; sd = params.sd;
  60                 seedLen = params.seedLen;
  61                 needCalcConPrb = true;
  62
  63                 ori = NULL; gld = NULL; mld = NULL; rspd = NULL; qd = NULL; qpro = NULL; nqpro = NULL;
  64                 mw = NULL;
  65
  66                 if (isMaster) {
  67                         gld = new LenDist(params.minL, params.maxL);
  68                         if (mean >= EPSILON) {
  69                                 mld = new LenDist(params.mate_minL, params.mate_maxL);
  70                         }
  71                         if (!estRSPD) { rspd = new RSPD(estRSPD); }
  72                         qd = new QualDist();
  73                 }
  74
  75                 ori = new Orientation(params.probF);
  76                 if (estRSPD) { rspd = new RSPD(estRSPD, params.B); }
  77                 qpro = new QProfile();
  78                 nqpro = new NoiseQProfile();
  79         }
  80
  81         ~SingleQModel() {
  82                 refs = NULL;
  83                 if (ori != NULL) delete ori;
  84                 if (gld != NULL) delete gld;
  85                 if (mld != NULL) delete mld;
  86                 if (rspd != NULL) delete rspd;
  87                 if (qd != NULL) delete qd;
  88                 if (qpro != NULL) delete qpro;
  89                 if (nqpro != NULL) delete nqpro;
  90                 if (mw != NULL) delete[] mw;
  91                 /*delete[] p1, p2;*/
  92         }
  93
  94         //SingleQModel& operator=(const SingleQModel&);
  95
  96         void estimateFromReads(const char*);
  97
  98         //if prob is too small, just make it 0
  99         double getConPrb(const SingleReadQ& read, const SingleHit& hit) const {
 100                 if (read.isLowQuality()) return 0.0;
 101
 102                 double prob;
 103                 int sid = hit.getSid();
 104                 RefSeq &ref = refs->getRef(sid);
 105                 int fullLen = ref.getFullLen();
 106                 int totLen = ref.getTotLen();
 107                 int dir = hit.getDir();
 108                 int pos = hit.getPos();
 109                 int readLen = read.getReadLength();
 110                 int fpos = (dir == 0 ? pos : totLen - pos - readLen); // the aligned position reported in SAM file, should be a coordinate in forward strand
 111
 112                 general_assert(fpos >= 0, "The alignment of read " + read.getName() + " to transcript " + itos(sid) + " starts at " + itos(fpos) + \
 113                                 " from the forward direction, which should be a non-negative number! " + \
 114                                 "It is possible that the aligner you use gave different read lengths for a same read in SAM file.");
 115                 general_assert(fpos + readLen <= totLen,"Read " + read.getName() + " is hung over the end of transcript " + itos(sid) + "! " \
 116                                 + "It is possible that the aligner you use gave different read lengths for a same read in SAM file.");
 117                 general_assert(readLen <= totLen, "Read " + read.getName() + " has length " + itos(readLen) + ", but it is aligned to transcript " \
 118                                 + itos(sid) + ", whose length (" + itos(totLen) + ") is shorter than the read's length!");
 119
 120                 int seedPos = (dir == 0 ? pos : totLen - pos - seedLen); // the aligned position of the seed in forward strand coordinates
 121                 if (seedPos >= fullLen || ref.getMask(seedPos)) return 0.0;
 122
 123                 int effL;
 124                 double value;
 125
 126                 if (mld != NULL) {
 127                         int minL = std::max(readLen, gld->getMinL());
 128                         int maxL = std::min(totLen - pos, gld->getMaxL());
 129                         int pfpos; // possible fpos for fragment
 130                         value = 0.0;
 131                         for (int fragLen = minL; fragLen <= maxL; fragLen++) {
 132                                 pfpos = (dir == 0 ? pos : totLen - pos - fragLen);
 133                                 effL = std::min(fullLen, totLen - fragLen + 1);
 134                                 value += gld->getAdjustedProb(fragLen, totLen) * rspd->getAdjustedProb(pfpos, effL, fullLen) * mld->getAdjustedProb(readLen, fragLen);
 135                         }
 136                 }
 137                 else {
 138                         effL = std::min(fullLen, totLen - readLen + 1);
 139                         value = gld->getAdjustedProb(readLen, totLen) * rspd->getAdjustedProb(fpos, effL, fullLen);
 140                 }
 141
 142                 prob = ori->getProb(dir) * value * qpro->getProb(read.getReadSeq(), read.getQScore(), ref, pos, dir);
 143
 144                 if (prob < EPSILON) { prob = 0.0; }
 145
 146                 prob = (mw[sid] < EPSILON ? 0.0 : prob / mw[sid]);
 147
 148                 return prob;
 149         }
 150
 151         double getNoiseConPrb(const SingleReadQ& read) {
 152                 if (read.isLowQuality()) return 0.0;
 153                 double prob = mld != NULL ? mld->getProb(read.getReadLength()) : gld->getProb(read.getReadLength());
 154                 prob *= nqpro->getProb(read.getReadSeq(), read.getQScore());
 155                 if (prob < EPSILON) { prob = 0.0; }
 156
 157                 prob = (mw[0] < EPSILON ? 0.0 : prob / mw[0]);
 158
 159                 return prob;
 160         }
 161
 162         double getLogP() { return nqpro->getLogP(); }
 163
 164         void init();
 165
 166         void update(const SingleReadQ& read, const SingleHit& hit, double frac) {
 167                 if (read.isLowQuality() || frac < EPSILON) return;
 168
 169                 const RefSeq& ref = refs->getRef(hit.getSid());
 170
 171                 int dir = hit.getDir();
 172                 int pos = hit.getPos();
 173
 174                 if (estRSPD) {
 175                         int fullLen = ref.getFullLen();
 176
 177                         // Only use one strand to estimate RSPD
 178                         if (ori->getProb(0) >= ORIVALVE && dir == 0) {
 179                                 rspd->update(pos, fullLen, frac);
 180                         }
 181
 182                         if (ori->getProb(0) < ORIVALVE && dir == 1) {
 183                                 int totLen = ref.getTotLen();
 184                                 int readLen = read.getReadLength();
 185
 186                                 int pfpos, effL;
 187
 188                                 if (mld != NULL) {
 189                                         int minL = std::max(readLen, gld->getMinL());
 190                                         int maxL = std::min(totLen - pos, gld->getMaxL());
 191                                         double sum = 0.0;
 192                                         assert(maxL >= minL);
 193                                         std::vector<double> frag_vec(maxL - minL + 1, 0.0);
 194
 195                                         for (int fragLen = minL; fragLen <= maxL; fragLen++) {
 196                                                 pfpos = totLen - pos - fragLen;
 197                                                 effL = std::min(fullLen, totLen - fragLen + 1);
 198                                                 frag_vec[fragLen - minL] = gld->getAdjustedProb(fragLen, totLen) * rspd->getAdjustedProb(pfpos, effL, fullLen) * mld->getAdjustedProb(readLen, fragLen);
 199                                                 sum += frag_vec[fragLen - minL];
 200                                         }
 201                                         assert(sum >= EPSILON);
 202                                         for (int fragLen = minL; fragLen <= maxL; fragLen++) {
 203                                                 pfpos = totLen - pos - fragLen;
 204                                                 rspd->update(pfpos, fullLen, frac * (frag_vec[fragLen - minL] / sum));
 205                                         }
 206                                 }
 207                                 else {
 208                                         rspd->update(totLen - pos - readLen, fullLen, frac);
 209                                 }
 210                         }
 211                 }
 212                 qpro->update(read.getReadSeq(), read.getQScore(), ref, pos, dir, frac);
 213         }
 214
 215         void updateNoise(const SingleReadQ& read, double frac) {
 216                 if (read.isLowQuality() || frac < EPSILON) return;
 217
 218                 nqpro->update(read.getReadSeq(), read.getQScore(), frac);
 219         }
 220
 221         void finish();
 222
 223         void collect(const SingleQModel&);
 224
 225         //void copy(const SingleQModel&);
 226
 227         bool getNeedCalcConPrb() { return needCalcConPrb; }
 228         void setNeedCalcConPrb(bool value) { needCalcConPrb = value; }
 229
 230         //void calcP1();
 231         //void calcP2();
 232         //double* getP1() { return p1; }
 233         //double* getP2() { return p2; }
 234
 235         void read(const char*);
 236         void write(const char*);
 237
 238         const LenDist& getGLD() { return *gld; }
 239
 240         void startSimulation(simul*, double*);
 241         bool simulate(int, SingleReadQ&, int&);
 242         void finishSimulation();
 243
 244         //Use it after function 'read' or 'estimateFromReads'
 245         double* getMW() {
 246           assert(mw != NULL);
 247           return mw;
 248         }
 249
 250         int getModelType() const { return model_type; }
 251
 252 private:
 253         static const int model_type = 1;
 254         static const int read_type = 1;
 255
 256         int M;
 257         int N[3];
 258         Refs *refs;
 259         double mean, sd;
 260         int seedLen;
 261         //double *p1, *p2; P_i' & P_i'';
 262
 263         bool estRSPD; // true if estimate RSPD
 264         bool needCalcConPrb; //true need, false does not need
 265
 266         Orientation *ori;
 267         LenDist *gld, *mld;
 268         RSPD *rspd;
 269         QualDist *qd;
 270         QProfile *qpro;
 271         NoiseQProfile *nqpro;
 272
 273         simul *sampler; // for simulation
 274         double *theta_cdf; // for simulation
 275
 276         double *mw; // for masking
 277
 278         void calcMW();
 279 };
 280
 281 void SingleQModel::estimateFromReads(const char* readFN) {
 282         int s;
 283         char readFs[2][STRLEN];
 284         SingleReadQ read;
 285
 286         mld != NULL ? mld->init() : gld->init();
 287         for (int i = 0; i < 3; i++)
 288                 if (N[i] > 0) {
 289                         genReadFileNames(readFN, i, read_type, s, readFs);
 290                         ReadReader<SingleReadQ> reader(s, readFs, refs->hasPolyA(), seedLen); // allow calculation of calc_lq() function
 291
 292                         int cnt = 0;
 293                         while (reader.next(read)) {
 294                                 if (!read.isLowQuality()) {
 295                                         mld != NULL ? mld->update(read.getReadLength(), 1.0) : gld->update(read.getReadLength(), 1.0);
 296                                         qd->update(read.getQScore());
 297                                         if (i == 0) { nqpro->updateC(read.getReadSeq(), read.getQScore()); }
 298                                 }
 299                                 else if (verbose && read.getReadLength() < seedLen) {
 300                                         printf("Warning: Read %s is ignored due to read length %d < seed length %d!\n", read.getName().c_str(), read.getReadLength(), seedLen);
 301                                 }
 302
 303                                 ++cnt;
 304                                 if (verbose && cnt % 1000000 == 0) { printf("%d READS PROCESSED\n", cnt); }
 305                         }
 306
 307                         if (verbose) { printf("estimateFromReads, N%d finished.\n", i); }
 308                 }
 309
 310         mld != NULL ? mld->finish() : gld->finish();
 311
 312         //mean should be > 0
 313         if (mean >= EPSILON) {
 314           assert(mld->getMaxL() <= gld->getMaxL());
 315           gld->setAsNormal(mean, sd, std::max(mld->getMinL(), gld->getMinL()), gld->getMaxL());
 316         }
 317         qd->finish();
 318         nqpro->calcInitParams();
 319
 320         mw = new double[M + 1];
 321         calcMW();
 322 }
 323
 324 void SingleQModel::init() {
 325         if (estRSPD) rspd->init();
 326         qpro->init();
 327         nqpro->init();
 328 }
 329
 330 void SingleQModel::finish() {
 331         if (estRSPD) rspd->finish();
 332         qpro->finish();
 333         nqpro->finish();
 334         needCalcConPrb = true;
 335         if (estRSPD) calcMW();
 336 }
 337
 338 void SingleQModel::collect(const SingleQModel& o) {
 339         if (estRSPD) rspd->collect(*(o.rspd));
 340         qpro->collect(*(o.qpro));
 341         nqpro->collect(*(o.nqpro));
 342 }
 343
 344 //Only master node can call
 345 void SingleQModel::read(const char* inpF) {
 346         int val;
 347         FILE *fi = fopen(inpF, "r");
 348         if (fi == NULL) { fprintf(stderr, "Cannot open %s! It may not exist.\n", inpF); exit(-1); }
 349
 350         assert(fscanf(fi, "%d", &val) == 1);
 351         assert(val == model_type);
 352
 353         ori->read(fi);
 354         gld->read(fi);
 355         assert(fscanf(fi, "%d", &val) == 1);
 356         if (val > 0) {
 357                 if (mld == NULL) mld = new LenDist();
 358                 mld->read(fi);
 359         }
 360         rspd->read(fi);
 361         qd->read(fi);
 362         qpro->read(fi);
 363         nqpro->read(fi);
 364
 365         if (fscanf(fi, "%d", &val) == 1) {
 366                 if (M == 0) M = val;
 367                 if (M == val) {
 368                         mw = new double[M + 1];
 369                         for (int i = 0; i <= M; i++) assert(fscanf(fi, "%lf", &mw[i]) == 1);
 370                 }
 371         }
 372
 373         fclose(fi);
 374 }
 375
 376 //Only master node can call. Only be called at EM.cpp
 377 void SingleQModel::write(const char* outF) {
 378         FILE *fo = fopen(outF, "w");
 379
 380         fprintf(fo, "%d\n", model_type);
 381         fprintf(fo, "\n");
 382
 383         ori->write(fo);  fprintf(fo, "\n");
 384         gld->write(fo);  fprintf(fo, "\n");
 385         if (mld != NULL) {
 386                 fprintf(fo, "1\n");
 387                 mld->write(fo);
 388         }
 389         else { fprintf(fo, "0\n"); }
 390         fprintf(fo, "\n");
 391         rspd->write(fo); fprintf(fo, "\n");
 392         qd->write(fo);   fprintf(fo, "\n");
 393         qpro->write(fo); fprintf(fo, "\n");
 394         nqpro->write(fo);
 395
 396         if (mw != NULL) {
 397           fprintf(fo, "\n%d\n", M);
 398           for (int i = 0; i < M; i++) {
 399             fprintf(fo, "%.15g ", mw[i]);
 400           }
 401           fprintf(fo, "%.15g\n", mw[M]);
 402         }
 403
 404         fclose(fo);
 405 }
 406
 407 void SingleQModel::startSimulation(simul* sampler, double* theta) {
 408         this->sampler = sampler;
 409
 410         theta_cdf = new double[M + 1];
 411         for (int i = 0; i <= M; i++) {
 412                 theta_cdf[i] = theta[i];
 413                 if (i > 0) theta_cdf[i] += theta_cdf[i - 1];
 414         }
 415
 416         rspd->startSimulation(M, refs);
 417         qd->startSimulation();
 418         qpro->startSimulation();
 419         nqpro->startSimulation();
 420 }
 421
 422 bool SingleQModel::simulate(int rid, SingleReadQ& read, int& sid) {
 423         int dir, pos, readLen, fragLen;
 424         std::string name;
 425         std::string qual, readseq;
 426         std::ostringstream strout;
 427
 428         sid = sampler->sample(theta_cdf, M + 1);
 429
 430         if (sid == 0) {
 431                 dir = pos = 0;
 432                 readLen = (mld != NULL ? mld->simulate(sampler, -1) : gld->simulate(sampler, -1));
 433                 qual = qd->simulate(sampler, readLen);
 434                 readseq = nqpro->simulate(sampler, readLen, qual);
 435         }
 436         else {
 437                 RefSeq &ref = refs->getRef(sid);
 438                 dir = ori->simulate(sampler);
 439                 fragLen = gld->simulate(sampler, ref.getTotLen());
 440                 if (fragLen < 0) return false;
 441
 442                 int effL = std::min(ref.getFullLen(), ref.getTotLen() - fragLen + 1);
 443                 pos = rspd->simulate(sampler, sid, effL);
 444                 if (pos < 0) return false;
 445                 if (dir > 0) pos = ref.getTotLen() - pos - fragLen;
 446
 447                 if (mld != NULL) {
 448                         readLen = mld->simulate(sampler, fragLen);
 449                         if (readLen < 0) return false;
 450                         qual = qd->simulate(sampler, readLen);
 451                         readseq = qpro->simulate(sampler, readLen, pos, dir, qual, ref);
 452                 }
 453                 else {
 454                         qual = qd->simulate(sampler, fragLen);
 455                         readseq = qpro->simulate(sampler, fragLen, pos, dir, qual, ref);
 456                 }
 457         }
 458
 459         strout<<rid<<"_"<<dir<<"_"<<sid<<"_"<<pos;
 460         name = strout.str();
 461
 462         read = SingleReadQ(name, readseq, qual);
 463
 464         return true;
 465 }
 466
 467 void SingleQModel::finishSimulation() {
 468         delete[] theta_cdf;
 469
 470         rspd->finishSimulation();
 471         qd->finishSimulation();
 472         qpro->finishSimulation();
 473         nqpro->finishSimulation();
 474 }
 475
 476 void SingleQModel::calcMW() {
 477         double probF, probR;
 478
 479         assert((mld == NULL ? gld->getMinL() : mld->getMinL()) >= seedLen);
 480
 481         memset(mw, 0, sizeof(double) * (M + 1));
 482         mw[0] = 1.0;
 483
 484         probF = ori->getProb(0);
 485         probR = ori->getProb(1);
 486
 487         for (int i = 1; i <= M; i++) {
 488                 RefSeq& ref = refs->getRef(i);
 489                 int totLen = ref.getTotLen();
 490                 int fullLen = ref.getFullLen();
 491                 double value = 0.0;
 492                 int minL, maxL;
 493                 int effL, pfpos;
 494                 int end = std::min(fullLen, totLen - seedLen + 1);
 495                 double factor;
 496
 497                 for (int seedPos = 0; seedPos < end; seedPos++)
 498                         if (ref.getMask(seedPos)) {
 499                                 //forward
 500                                 minL = gld->getMinL();
 501                                 maxL = std::min(gld->getMaxL(), totLen - seedPos);
 502                                 pfpos = seedPos;
 503                                 for (int fragLen = minL; fragLen <= maxL; fragLen++) {
 504                                         effL = std::min(fullLen, totLen - fragLen + 1);
 505                                         factor = (mld == NULL ? 1.0 : mld->getAdjustedCumulativeProb(std::min(mld->getMaxL(), fragLen), fragLen));
 506                                         value += probF * gld->getAdjustedProb(fragLen, totLen) * rspd->getAdjustedProb(pfpos, effL, fullLen) * factor;
 507                                 }
 508                                 //reverse
 509                                 minL = gld->getMinL();
 510                                 maxL = std::min(gld->getMaxL(), seedPos + seedLen);
 511                                 for (int fragLen = minL; fragLen <= maxL; fragLen++) {
 512                                         pfpos = seedPos - (fragLen - seedLen);
 513                                         effL = std::min(fullLen, totLen - fragLen + 1);
 514                                         factor = (mld == NULL ? 1.0 : mld->getAdjustedCumulativeProb(std::min(mld->getMaxL(), fragLen), fragLen));
 515                                         value += probR * gld->getAdjustedProb(fragLen, totLen) * rspd->getAdjustedProb(pfpos, effL, fullLen) * factor;
 516                                 }
 517                         }
 518
 519                 //for reverse strand masking
 520                 for (int seedPos = end; seedPos <= totLen - seedLen; seedPos++) {
 521                         minL = std::max(gld->getMinL(), seedPos + seedLen - fullLen + 1);
 522                         maxL = std::min(gld->getMaxL(), seedPos + seedLen);
 523                         for (int fragLen = minL; fragLen <= maxL; fragLen++) {
 524                                 pfpos = seedPos - (fragLen - seedLen);
 525                                 effL = std::min(fullLen, totLen - fragLen + 1);
 526                                 factor = (mld == NULL ? 1.0 : mld->getAdjustedCumulativeProb(std::min(mld->getMaxL(), fragLen), fragLen));
 527                                 value += probR * gld->getAdjustedProb(fragLen, totLen) * rspd->getAdjustedProb(pfpos, effL, fullLen) * factor;
 528                         }
 529                 }
 530
 531                 mw[i] = 1.0 - value;
 532
 533                 if (mw[i] < 1e-8) {
 534                         //      fprintf(stderr, "Warning: %dth reference sequence is masked for almost all positions!\n", i);
 535                         mw[i] = 0.0;
 536                 }
 537         }
 538 }
 539
 540 #endif /* SINGLEQMODEL_H_ */