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#ifndef PAIREDENDQMODEL_H_
#define PAIREDENDQMODEL_H_
#include<cmath>
#include<cstdio>
#include<cassert>
#include<cstring>
#include<string>
#include<algorithm>
#include<sstream>
#include<iostream>
#include<vector>
#include "utils.h"
#include "my_assert.h"
#include "Orientation.h"
#include "LenDist.h"
#include "RSPD.h"
#include "QualDist.h"
#include "QProfile.h"
#include "NoiseQProfile.h"
#include "ModelParams.h"
#include "RefSeq.h"
#include "Refs.h"
#include "SingleReadQ.h"
#include "PairedEndReadQ.h"
#include "PairedEndHit.h"
#include "ReadReader.h"
#include "simul.h"
class PairedEndQModel {
public:
PairedEndQModel(Refs* refs = NULL) {
this->refs = refs;
M = (refs != NULL ? refs->getM() : 0);
memset(N, 0, sizeof(N));
estRSPD = false;
needCalcConPrb = true;
ori = new Orientation();
gld = new LenDist();
rspd = new RSPD(estRSPD);
qd = new QualDist();
qpro = new QProfile();
nqpro = new NoiseQProfile();
mld = new LenDist();
mw = NULL;
seedLen = 0;
}
//If it is not a master node, only init & update can be used!
PairedEndQModel(ModelParams& params, bool isMaster = true) {
M = params.M;
memcpy(N, params.N, sizeof(params.N));
refs = params.refs;
estRSPD = params.estRSPD;
seedLen = params.seedLen;
needCalcConPrb = true;
ori = NULL; gld = NULL; rspd = NULL; qd = NULL; qpro = NULL; nqpro = NULL; mld = NULL;
mw = NULL;
if (isMaster) {
if (!estRSPD) rspd = new RSPD(estRSPD);
qd = new QualDist();
mld = new LenDist(params.mate_minL, params.mate_maxL);
}
ori = new Orientation(params.probF);
gld = new LenDist(params.minL, params.maxL);
if (estRSPD) rspd = new RSPD(estRSPD, params.B);
qpro = new QProfile();
nqpro = new NoiseQProfile();
}
~PairedEndQModel() {
refs = NULL;
if (ori != NULL) delete ori;
if (gld != NULL) delete gld;
if (rspd != NULL) delete rspd;
if (qd != NULL) delete qd;
if (qpro != NULL) delete qpro;
if (nqpro != NULL) delete nqpro;
if (mld != NULL) delete mld;
if (mw != NULL) delete mw;
}
void estimateFromReads(const char*);
//if prob is too small, just make it 0
double getConPrb(const PairedEndReadQ& read, const PairedEndHit& hit) {
if (read.isLowQuality()) return 0.0;
double prob;
int sid = hit.getSid();
RefSeq &ref = refs->getRef(sid);
int dir = hit.getDir();
int pos = hit.getPos();
int fullLen = ref.getFullLen();
int totLen = ref.getTotLen();
int insertLen = hit.getInsertL();
int fpos = (dir == 0 ? pos : totLen - pos - insertLen); // the aligned position reported in SAM file, should be a coordinate in forward strand
int effL = std::min(fullLen, totLen - insertLen + 1);
general_assert(fpos >= 0, "The alignment of fragment " + read.getName() + " to transcript " + itos(sid) + " starts at " + itos(fpos) + \
" from the forward direction, which should be a non-negative number! " + \
"It is possible that the aligner you use gave different read lengths for a same read in SAM file.");
general_assert(fpos + insertLen <= totLen,"Fragment " + read.getName() + " is hung over the end of transcript " + itos(sid) + "! " \
+ "It is possible that the aligner you use gave different read lengths for a same read in SAM file.");
general_assert(insertLen <= totLen, "Fragment " + read.getName() + " has length " + itos(insertLen) + ", but it is aligned to transcript " \
+ itos(sid) + ", whose length (" + itos(totLen) + ") is shorter than the fragment's length!");
if (fpos >= fullLen || ref.getMask(fpos)) return 0.0; // For paired-end model, fpos is the seedPos
prob = ori->getProb(dir) * gld->getAdjustedProb(insertLen, totLen) *
rspd->getAdjustedProb(fpos, effL, fullLen);
const SingleReadQ& mate1 = read.getMate1();
prob *= mld->getAdjustedProb(mate1.getReadLength(), insertLen) *
qpro->getProb(mate1.getReadSeq(), mate1.getQScore(), ref, pos, dir);
const SingleReadQ& mate2 = read.getMate2();
int m2pos = totLen - pos - insertLen;
int m2dir = !dir;
prob *= mld->getAdjustedProb(mate2.getReadLength(), hit.getInsertL()) *
qpro->getProb(mate2.getReadSeq(), mate2.getQScore(), ref, m2pos, m2dir);
if (prob < EPSILON) { prob = 0.0; }
prob = (mw[sid] < EPSILON ? 0.0 : prob / mw[sid]);
return prob;
}
double getNoiseConPrb(const PairedEndReadQ& read) {
if (read.isLowQuality()) return 0.0;
double prob;
const SingleReadQ& mate1 = read.getMate1();
const SingleReadQ& mate2 = read.getMate2();
prob = mld->getProb(mate1.getReadLength()) * nqpro->getProb(mate1.getReadSeq(), mate1.getQScore());
prob *= mld->getProb(mate2.getReadLength()) * nqpro->getProb(mate2.getReadSeq(), mate2.getQScore());
if (prob < EPSILON) { prob = 0.0; }
prob = (mw[0] < EPSILON ? 0.0: prob / mw[0]);
return prob;
}
double getLogP() { return nqpro->getLogP(); }
void init();
void update(const PairedEndReadQ& read, const PairedEndHit& hit, double frac) {
if (read.isLowQuality() || frac < EPSILON) return;
RefSeq& ref = refs->getRef(hit.getSid());
const SingleReadQ& mate1 = read.getMate1();
const SingleReadQ& mate2 = read.getMate2();
gld->update(hit.getInsertL(), frac);
if (estRSPD) {
int fpos = (hit.getDir() == 0 ? hit.getPos() : ref.getTotLen() - hit.getPos() - hit.getInsertL());
rspd->update(fpos, ref.getFullLen(), frac);
}
qpro->update(mate1.getReadSeq(), mate1.getQScore(), ref, hit.getPos(), hit.getDir(), frac);
int m2pos = ref.getTotLen() - hit.getPos() - hit.getInsertL();
int m2dir = !hit.getDir();
qpro->update(mate2.getReadSeq(), mate2.getQScore(), ref, m2pos, m2dir, frac);
}
void updateNoise(const PairedEndReadQ& read, double frac) {
if (read.isLowQuality() || frac < EPSILON) return;
const SingleReadQ& mate1 = read.getMate1();
const SingleReadQ& mate2 = read.getMate2();
nqpro->update(mate1.getReadSeq(), mate1.getQScore(), frac);
nqpro->update(mate2.getReadSeq(), mate2.getQScore(), frac);
}
void finish();
void collect(const PairedEndQModel&);
bool getNeedCalcConPrb() { return needCalcConPrb; }
void setNeedCalcConPrb(bool value) { needCalcConPrb = value; }
void read(const char*);
void write(const char*);
const LenDist& getGLD() { return *gld; }
void startSimulation(simul*, const std::vector<double>&);
bool simulate(READ_INT_TYPE, PairedEndReadQ&, int&);
void finishSimulation();
//Use it after function 'read' or 'estimateFromReads'
const double* getMW() {
assert(mw != NULL);
return mw;
}
int getModelType() const { return model_type; }
private:
static const int model_type = 3;
static const int read_type = 3;
int M;
READ_INT_TYPE N[3];
Refs *refs;
int seedLen;
bool estRSPD;
bool needCalcConPrb; //true need, false does not need
Orientation *ori;
LenDist *gld, *mld; //mld1 mate_length_dist
RSPD *rspd;
QualDist *qd;
QProfile *qpro;
NoiseQProfile *nqpro;
simul *sampler; // for simulation
double *theta_cdf; // for simulation
double *mw; // for masking
void calcMW();
};
void PairedEndQModel::estimateFromReads(const char* readFN) {
int s;
char readFs[2][STRLEN];
PairedEndReadQ read;
int n_warns = 0;
mld->init();
for (int i = 0; i < 3; i++)
if (N[i] > 0) {
genReadFileNames(readFN, i, read_type, s, readFs);
ReadReader<PairedEndReadQ> reader(s, readFs, refs->hasPolyA(), seedLen); // allow calculation of calc_lq() function
READ_INT_TYPE cnt = 0;
while (reader.next(read)) {
SingleReadQ mate1 = read.getMate1();
SingleReadQ mate2 = read.getMate2();
if (!read.isLowQuality()) {
mld->update(mate1.getReadLength(), 1.0);
mld->update(mate2.getReadLength(), 1.0);
qd->update(mate1.getQScore());
qd->update(mate2.getQScore());
if (i == 0) {
nqpro->updateC(mate1.getReadSeq(), mate1.getQScore());
nqpro->updateC(mate2.getReadSeq(), mate2.getQScore());
}
}
else if (mate1.getReadLength() < seedLen || mate2.getReadLength() < seedLen)
if (n_warns <= MAX_WARNS)
fprintf(stderr, "Warning: Read %s is ignored due to at least one of the mates' length < seed length (= %d)!\n", read.getName().c_str(), seedLen);
++cnt;
if (verbose && cnt % 1000000 == 0) { std::cout<< cnt<< " READS PROCESSED"<< std::endl; }
}
if (verbose) { std::cout<<"estimateFromReads, N"<< i<<" finished."<< std::endl; }
}
if (n_warns > 0) fprintf(stderr, "Warning: There are %d reads ignored in total.\n", n_warns);
mld->finish();
qd->finish();
nqpro->calcInitParams();
mw = new double[M + 1];
calcMW();
}
void PairedEndQModel::init() {
gld->init();
if (estRSPD) rspd->init();
qpro->init();
nqpro->init();
}
void PairedEndQModel::finish() {
gld->finish();
if (estRSPD) rspd->finish();
qpro->finish();
nqpro->finish();
needCalcConPrb = true;
calcMW();
}
void PairedEndQModel::collect(const PairedEndQModel& o) {
gld->collect(*(o.gld));
if (estRSPD) rspd->collect(*(o.rspd));
qpro->collect(*(o.qpro));
nqpro->collect(*(o.nqpro));
}
//Only master node can call
void PairedEndQModel::read(const char* inpF) {
int val;
FILE *fi = fopen(inpF, "r");
general_assert(fi != NULL, "Cannot open " + cstrtos(inpF) + "! It may not exist.");
assert(fscanf(fi, "%d", &val) == 1);
assert(val == model_type);
ori->read(fi);
gld->read(fi);
mld->read(fi);
rspd->read(fi);
qd->read(fi);
qpro->read(fi);
nqpro->read(fi);
if (fscanf(fi, "%d", &val) == 1) {
if (M == 0) M = val;
if (M == val) {
mw = new double[M + 1];
for (int i = 0; i <= M; i++) assert(fscanf(fi, "%lf", &mw[i]) == 1);
}
}
fclose(fi);
}
//Only master node can call. Only be called at EM.cpp
void PairedEndQModel::write(const char* outF) {
FILE *fo = fopen(outF, "w");
fprintf(fo, "%d\n", model_type);
fprintf(fo, "\n");
ori->write(fo); fprintf(fo, "\n");
gld->write(fo); fprintf(fo, "\n");
mld->write(fo); fprintf(fo, "\n");
rspd->write(fo); fprintf(fo, "\n");
qd->write(fo); fprintf(fo, "\n");
qpro->write(fo); fprintf(fo, "\n");
nqpro->write(fo);
if (mw != NULL) {
fprintf(fo, "\n%d\n", M);
for (int i = 0; i < M; i++) {
fprintf(fo, "%.15g ", mw[i]);
}
fprintf(fo, "%.15g\n", mw[M]);
}
fclose(fo);
}
void PairedEndQModel::startSimulation(simul* sampler, const std::vector<double>& theta) {
this->sampler = sampler;
theta_cdf = new double[M + 1];
for (int i = 0; i <= M; i++) {
theta_cdf[i] = theta[i];
if (i > 0) theta_cdf[i] += theta_cdf[i - 1];
}
rspd->startSimulation(M, refs);
qd->startSimulation();
qpro->startSimulation();
nqpro->startSimulation();
}
bool PairedEndQModel::simulate(READ_INT_TYPE rid, PairedEndReadQ& read, int& sid) {
int dir, pos;
int insertL, mateL1, mateL2;
std::string name;
std::string qual1, qual2, readseq1, readseq2;
std::ostringstream strout;
sid = sampler->sample(theta_cdf, M + 1);
if (sid == 0) {
dir = pos = insertL = 0;
mateL1 = mld->simulate(sampler, -1);
qual1 = qd->simulate(sampler, mateL1);
readseq1 = nqpro->simulate(sampler, mateL1, qual1);
mateL2 = mld->simulate(sampler, -1);
qual2 = qd->simulate(sampler, mateL2);
readseq2 = nqpro->simulate(sampler, mateL2, qual2);
}
else {
RefSeq &ref = refs->getRef(sid);
dir = ori->simulate(sampler);
insertL = gld->simulate(sampler, ref.getTotLen());
if (insertL < 0) return false;
int effL = std::min(ref.getFullLen(), ref.getTotLen() - insertL + 1);
pos = rspd->simulate(sampler, sid, effL);
if (pos < 0) return false;
if (dir > 0) pos = ref.getTotLen() - pos - insertL;
mateL1 = mld->simulate(sampler, insertL);
qual1 = qd->simulate(sampler, mateL1);
readseq1 = qpro->simulate(sampler, mateL1, pos, dir, qual1, ref);
int m2pos = ref.getTotLen() - pos - insertL;
int m2dir = !dir;
mateL2 = mld->simulate(sampler, insertL);
qual2 = qd->simulate(sampler, mateL2);
readseq2 = qpro->simulate(sampler, mateL2, m2pos, m2dir, qual2, ref);
}
strout<<rid<<"_"<<dir<<"_"<<sid<<"_"<<pos<<"_"<<insertL;
name = strout.str();
read = PairedEndReadQ(SingleReadQ(name + "/1", readseq1, qual1), SingleReadQ(name + "/2", readseq2, qual2));
return true;
}
void PairedEndQModel::finishSimulation() {
delete[] theta_cdf;
rspd->finishSimulation();
qd->finishSimulation();
qpro->finishSimulation();
nqpro->finishSimulation();
}
void PairedEndQModel::calcMW() {
assert(mld->getMinL() >= seedLen);
memset(mw, 0, sizeof(double) * (M + 1));
mw[0] = 1.0;
for (int i = 1; i <= M; i++) {
RefSeq& ref = refs->getRef(i);
int totLen = ref.getTotLen();
int fullLen = ref.getFullLen();
int end = std::min(fullLen, totLen - gld->getMinL() + 1);
double value = 0.0;
int minL, maxL;
int effL, pfpos;
//seedPos is fpos here
for (int seedPos = 0; seedPos < end; seedPos++)
if (ref.getMask(seedPos)) {
minL = gld->getMinL();
maxL = std::min(gld->getMaxL(), totLen - seedPos);
pfpos = seedPos;
for (int fragLen = minL; fragLen <= maxL; fragLen++) {
effL = std::min(fullLen, totLen - fragLen + 1);
value += gld->getAdjustedProb(fragLen, totLen) * rspd->getAdjustedProb(pfpos, effL, fullLen);
}
}
mw[i] = 1.0 - value;
if (mw[i] < 1e-8) {
// fprintf(stderr, "Warning: %dth reference sequence is masked for almost all positions!\n", i);
mw[i] = 0.0;
}
}
}
#endif /* PAIREDENDQMODEL_H_ */
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