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#include<cstdio>
#include<cstring>
#include<cstdlib>
#include<cassert>
#include<fstream>
#include<sstream>
#include<vector>
#include<pthread.h>
#include "utils.h"
#include "my_assert.h"
#include "sampling.h"
#include "Model.h"
#include "SingleModel.h"
#include "SingleQModel.h"
#include "PairedEndModel.h"
#include "PairedEndQModel.h"
#include "Refs.h"
#include "GroupInfo.h"
#include "WriteResults.h"
using namespace std;
bool verbose = true;
struct Params {
int no, nsamples;
FILE *fo;
engine_type *engine;
double *pme_c, *pve_c; //posterior mean and variance vectors on counts
double *pme_tpm, *pme_fpkm;
double *pve_c_genes, *pve_c_trans;
};
struct Item {
int sid;
double conprb;
Item(int sid, double conprb) {
this->sid = sid;
this->conprb = conprb;
}
};
int nThreads;
int model_type;
int M;
READ_INT_TYPE N0, N1;
HIT_INT_TYPE nHits;
double totc;
int BURNIN, NSAMPLES, GAP;
char refName[STRLEN], imdName[STRLEN], statName[STRLEN];
char thetaF[STRLEN], ofgF[STRLEN], refF[STRLEN], modelF[STRLEN];
char cvsF[STRLEN];
Refs refs;
vector<HIT_INT_TYPE> s;
vector<Item> hits;
vector<double> eel;
double *mw;
vector<int> init_counts;
double pseudoC;
vector<double> pme_c, pve_c; //global posterior mean and variance vectors on counts
vector<double> pme_tpm, pme_fpkm;
bool quiet;
Params *paramsArray;
pthread_t *threads;
pthread_attr_t attr;
int rc;
bool hasSeed;
seedType seed;
int m;
char groupF[STRLEN];
GroupInfo gi;
bool alleleS;
int m_trans;
GroupInfo gt, ta;
vector<double> pve_c_genes, pve_c_trans;
// pliu
// if has prior file; file's name; and a vector to save prior parameters
bool has_prior;
char fprior[STRLEN];
vector<double> pseudo_counts;
//////
void load_data(char* refName, char* statName, char* imdName) {
ifstream fin;
string line;
int tmpVal;
//load reference file
sprintf(refF, "%s.seq", refName);
refs.loadRefs(refF, 1);
M = refs.getM();
//load ofgF;
sprintf(ofgF, "%s.ofg", imdName);
fin.open(ofgF);
general_assert(fin.is_open(), "Cannot open " + cstrtos(ofgF) + "!");
fin>>tmpVal>>N0;
general_assert(tmpVal == M, "M in " + cstrtos(ofgF) + " is not consistent with " + cstrtos(refF) + "!");
getline(fin, line);
s.clear(); hits.clear();
s.push_back(0);
while (getline(fin, line)) {
istringstream strin(line);
int sid;
double conprb;
while (strin>>sid>>conprb) {
hits.push_back(Item(sid, conprb));
}
s.push_back(hits.size());
}
fin.close();
N1 = s.size() - 1;
nHits = hits.size();
if (verbose) { printf("Loading data is finished!\n"); }
}
void load_group_info(char* refName) {
// Load group info
sprintf(groupF, "%s.grp", refName);
gi.load(groupF);
m = gi.getm();
alleleS = isAlleleSpecific(refName, >, &ta); // if allele-specific
m_trans = (alleleS ? ta.getm() : 0);
if (verbose) { printf("Loading group information is finished!\n"); }
}
// Load imdName.omit and initialize the init count vector.
void load_omit_info(const char* imdName) {
char omitF[STRLEN];
FILE *fi = NULL;
int tid;
sprintf(omitF, "%s.omit", imdName);
fi = fopen(omitF, "r");
init_counts.assign(M + 1, 0);
totc = M + 1;
while (fscanf(fi, "%d", &tid) == 1) {
init_counts[tid] = -1;
--totc;
}
fclose(fi);
totc = totc * pseudoC + N0 + N1;
}
// pliu
// load isoform's prior information and re-calculate totc
void load_prior_info(const char* fprior){
pseudo_counts.assign(M+1, 0.0);
ifstream fin;
string line;
fin.open(fprior);
for(int i=1; i<=M; ++i){
double prior;
getline(fin, line);
sscanf(line.c_str(), "%lf%*s", &prior);
if ( init_counts[i] == 0 ){ // not to-be-omitted
pseudo_counts[i] = prior;
}
}
fin.close();
// re-calculate 'totc' by considering prior parameters
totc = 1;
for ( int i=1; i<=M; ++i ) {
if ( init_counts[i] == 0 ) { // not to-be-omitted
totc += pseudo_counts[i];
}
}
totc += N0 + N1;
}
//////
template<class ModelType>
void init_model_related(char* modelF) {
ModelType model;
model.read(modelF);
calcExpectedEffectiveLengths<ModelType>(M, refs, model, eel);
memcpy(mw, model.getMW(), sizeof(double) * (M + 1)); // otherwise, after exiting this procedure, mw becomes undefined
}
// assign threads
void init() {
int quotient, left;
char outF[STRLEN];
quotient = NSAMPLES / nThreads;
left = NSAMPLES % nThreads;
sprintf(cvsF, "%s.countvectors", imdName);
paramsArray = new Params[nThreads];
threads = new pthread_t[nThreads];
hasSeed ? engineFactory::init(seed) : engineFactory::init();
for (int i = 0; i < nThreads; i++) {
paramsArray[i].no = i;
paramsArray[i].nsamples = quotient;
if (i < left) paramsArray[i].nsamples++;
sprintf(outF, "%s%d", cvsF, i);
paramsArray[i].fo = fopen(outF, "w");
paramsArray[i].engine = engineFactory::new_engine();
paramsArray[i].pme_c = new double[M + 1];
memset(paramsArray[i].pme_c, 0, sizeof(double) * (M + 1));
paramsArray[i].pve_c = new double[M + 1];
memset(paramsArray[i].pve_c, 0, sizeof(double) * (M + 1));
paramsArray[i].pme_tpm = new double[M + 1];
memset(paramsArray[i].pme_tpm, 0, sizeof(double) * (M + 1));
paramsArray[i].pme_fpkm = new double[M + 1];
memset(paramsArray[i].pme_fpkm, 0, sizeof(double) * (M + 1));
paramsArray[i].pve_c_genes = new double[m];
memset(paramsArray[i].pve_c_genes, 0, sizeof(double) * m);
paramsArray[i].pve_c_trans = NULL;
if (alleleS) {
paramsArray[i].pve_c_trans = new double[m_trans];
memset(paramsArray[i].pve_c_trans, 0, sizeof(double) * m_trans);
}
}
engineFactory::finish();
/* set thread attribute to be joinable */
pthread_attr_init(&attr);
pthread_attr_setdetachstate(&attr, PTHREAD_CREATE_JOINABLE);
if (verbose) { printf("Initialization finished!\n"); }
}
void writeCountVector(FILE* fo, vector<int>& counts) {
for (int i = 0; i < M; i++) {
fprintf(fo, "%d ", counts[i]);
}
fprintf(fo, "%d\n", counts[M]);
}
void* Gibbs(void* arg) {
int CHAINLEN;
HIT_INT_TYPE len, fr, to;
Params *params = (Params*)arg;
vector<double> theta, tpm, fpkm;
vector<int> z, counts(init_counts);
vector<double> arr;
uniform_01_generator rg(*params->engine, uniform_01_dist());
// generate initial state
theta.assign(M + 1, 0.0);
z.assign(N1, 0);
counts[0] += N0;
for (READ_INT_TYPE i = 0; i < N1; i++) {
fr = s[i]; to = s[i + 1];
len = to - fr;
arr.assign(len, 0);
for (HIT_INT_TYPE j = fr; j < to; j++) {
arr[j - fr] = hits[j].conprb;
if (j > fr) arr[j - fr] += arr[j - fr - 1]; // cumulative
}
z[i] = hits[fr + sample(rg, arr, len)].sid;
++counts[z[i]];
}
// Gibbs sampling
CHAINLEN = 1 + (params->nsamples - 1) * GAP;
for (int ROUND = 1; ROUND <= BURNIN + CHAINLEN; ROUND++) {
for (READ_INT_TYPE i = 0; i < N1; i++) {
--counts[z[i]];
fr = s[i]; to = s[i + 1]; len = to - fr;
arr.assign(len, 0);
for (HIT_INT_TYPE j = fr; j < to; j++) {
if ( has_prior ) {
arr[j - fr] = (counts[hits[j].sid] + pseudo_counts[hits[j].sid]) * hits[j].conprb;
} else {
arr[j - fr] = (counts[hits[j].sid] + pseudoC) * hits[j].conprb;
}
if (j > fr) arr[j - fr] += arr[j - fr - 1]; //cumulative
}
z[i] = hits[fr + sample(rg, arr, len)].sid;
++counts[z[i]];
}
if (ROUND > BURNIN) {
if ((ROUND - BURNIN - 1) % GAP == 0) {
writeCountVector(params->fo, counts);
for (int i = 0; i <= M; i++) {
if ( has_prior ) {
theta[i] = (counts[i] < 0 ? 0.0 : (counts[i] + pseudo_counts[i]) / totc);
} else {
theta[i] = (counts[i] < 0 ? 0.0 : (counts[i] + pseudoC) / totc);
}
}
polishTheta(M, theta, eel, mw);
calcExpressionValues(M, theta, eel, tpm, fpkm);
for (int i = 0; i <= M; i++) {
params->pme_c[i] += counts[i];
params->pve_c[i] += double(counts[i]) * counts[i];
params->pme_tpm[i] += tpm[i];
params->pme_fpkm[i] += fpkm[i];
}
for (int i = 0; i < m; i++) {
int b = gi.spAt(i), e = gi.spAt(i + 1);
double count = 0.0;
for (int j = b; j < e; j++) count += counts[j];
params->pve_c_genes[i] += count * count;
}
if (alleleS)
for (int i = 0; i < m_trans; i++) {
int b = ta.spAt(i), e = ta.spAt(i + 1);
double count = 0.0;
for (int j = b; j < e; j++) count += counts[j];
params->pve_c_trans[i] += count * count;
}
}
}
if (verbose && ROUND % 100 == 0) { printf("Thread %d, ROUND %d is finished!\n", params->no, ROUND); }
}
return NULL;
}
void release() {
// char inpF[STRLEN], command[STRLEN];
string line;
/* destroy attribute */
pthread_attr_destroy(&attr);
delete[] threads;
pme_c.assign(M + 1, 0);
pve_c.assign(M + 1, 0);
pme_tpm.assign(M + 1, 0);
pme_fpkm.assign(M + 1, 0);
pve_c_genes.assign(m, 0);
pve_c_trans.clear();
if (alleleS) pve_c_trans.assign(m_trans, 0);
for (int i = 0; i < nThreads; i++) {
fclose(paramsArray[i].fo);
delete paramsArray[i].engine;
for (int j = 0; j <= M; j++) {
pme_c[j] += paramsArray[i].pme_c[j];
pve_c[j] += paramsArray[i].pve_c[j];
pme_tpm[j] += paramsArray[i].pme_tpm[j];
pme_fpkm[j] += paramsArray[i].pme_fpkm[j];
}
for (int j = 0; j < m; j++)
pve_c_genes[j] += paramsArray[i].pve_c_genes[j];
if (alleleS)
for (int j = 0; j < m_trans; j++)
pve_c_trans[j] += paramsArray[i].pve_c_trans[j];
delete[] paramsArray[i].pme_c;
delete[] paramsArray[i].pve_c;
delete[] paramsArray[i].pme_tpm;
delete[] paramsArray[i].pme_fpkm;
delete[] paramsArray[i].pve_c_genes;
if (alleleS) delete[] paramsArray[i].pve_c_trans;
}
delete[] paramsArray;
for (int i = 0; i <= M; i++) {
pme_c[i] /= NSAMPLES;
pve_c[i] = (pve_c[i] - double(NSAMPLES) * pme_c[i] * pme_c[i]) / double(NSAMPLES - 1);
if (pve_c[i] < 0.0) pve_c[i] = 0.0;
pme_tpm[i] /= NSAMPLES;
pme_fpkm[i] /= NSAMPLES;
}
for (int i = 0; i < m; i++) {
int b = gi.spAt(i), e = gi.spAt(i + 1);
double pme_c_gene = 0.0;
for (int j = b; j < e; j++) pme_c_gene += pme_c[j];
pve_c_genes[i] = (pve_c_genes[i] - double(NSAMPLES) * pme_c_gene * pme_c_gene) / double(NSAMPLES - 1);
if (pve_c_genes[i] < 0.0) pve_c_genes[i] = 0.0;
}
if (alleleS)
for (int i = 0; i < m_trans; i++) {
int b = ta.spAt(i), e = ta.spAt(i + 1);
double pme_c_tran = 0.0;
for (int j = b; j < e; j++) pme_c_tran += pme_c[j];
pve_c_trans[i] = (pve_c_trans[i] - double(NSAMPLES) * pme_c_tran * pme_c_tran) / double(NSAMPLES - 1);
if (pve_c_trans[i] < 0.0) pve_c_trans[i] = 0.0;
}
}
int main(int argc, char* argv[]) {
if (argc < 7) {
// pliu
// add an option --prior to take priors
printf("Usage: rsem-run-gibbs reference_name imdName statName BURNIN NSAMPLES GAP [-p #Threads] [--seed seed] [--pseudo-count pseudo_count] [--prior file] [-q]\n");
printf("\n");
printf("Format of the prior file:\n");
printf("- One isoform's prior per line\n");
printf("- Priors must be in the same order as in the .ti file\n");
printf("- Priors for those to-be-omitted isoforms must be included as well\n");
printf("- Comments can be added after prior separated by space(s)\n");
exit(-1);
}
strcpy(refName, argv[1]);
strcpy(imdName, argv[2]);
strcpy(statName, argv[3]);
BURNIN = atoi(argv[4]);
NSAMPLES = atoi(argv[5]);
GAP = atoi(argv[6]);
nThreads = 1;
hasSeed = false;
pseudoC = 1.0;
quiet = false;
// pliu
has_prior = false;
//////
for (int i = 7; i < argc; i++) {
if (!strcmp(argv[i], "-p")) nThreads = atoi(argv[i + 1]);
if (!strcmp(argv[i], "--seed")) {
hasSeed = true;
int len = strlen(argv[i + 1]);
seed = 0;
for (int k = 0; k < len; k++) seed = seed * 10 + (argv[i + 1][k] - '0');
}
if (!strcmp(argv[i], "--pseudo-count")) pseudoC = atof(argv[i + 1]);
if (!strcmp(argv[i], "-q")) quiet = true;
// pliu
if ( ! strcmp(argv[i], "--prior") ) {
has_prior = true;
strcpy(fprior, argv[i+1]);
}
//////
}
verbose = !quiet;
assert(NSAMPLES > 1); // Otherwise, we cannot calculate posterior variance
if (nThreads > NSAMPLES) {
nThreads = NSAMPLES;
fprintf(stderr, "Warning: Number of samples is less than number of threads! Change the number of threads to %d!\n", nThreads);
}
load_data(refName, statName, imdName);
load_group_info(refName);
load_omit_info(imdName);
// pliu
// have to do it after load_data() in order to use 'M'
// the variable 'totc' will be re-calculated by including the prior info
if ( has_prior ) {
load_prior_info(fprior);
}
//////
sprintf(modelF, "%s.model", statName);
FILE *fi = fopen(modelF, "r");
general_assert(fi != NULL, "Cannot open " + cstrtos(modelF) + "!");
assert(fscanf(fi, "%d", &model_type) == 1);
fclose(fi);
mw = new double[M + 1]; // make an extra copy
switch(model_type) {
case 0 : init_model_related<SingleModel>(modelF); break;
case 1 : init_model_related<SingleQModel>(modelF); break;
case 2 : init_model_related<PairedEndModel>(modelF); break;
case 3 : init_model_related<PairedEndQModel>(modelF); break;
}
if (verbose) printf("Gibbs started!\n");
init();
for (int i = 0; i < nThreads; i++) {
rc = pthread_create(&threads[i], &attr, Gibbs, (void*)(¶msArray[i]));
pthread_assert(rc, "pthread_create", "Cannot create thread " + itos(i) + " (numbered from 0)!");
}
for (int i = 0; i < nThreads; i++) {
rc = pthread_join(threads[i], NULL);
pthread_assert(rc, "pthread_join", "Cannot join thread " + itos(i) + " (numbered from 0)!");
}
release();
if (verbose) printf("Gibbs finished!\n");
writeResultsGibbs(M, m, m_trans, gi, gt, ta, alleleS, imdName, pme_c, pme_fpkm, pme_tpm, pve_c, pve_c_genes, pve_c_trans);
delete mw; // delete the copy
return 0;
}
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