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//////////////////////////////////////////////////////////////////////
// Main.cc
//////////////////////////////////////////////////////////////////////
#include <errno.h>
#include <stdio.h>
#include <stdlib.h>
#include <string.h>
#include <vector>
#include <climits>
#include "Assert.h"
#include "MultiSequence.h"
#include "ProbModel.h"
#include "Matrix.h"
#include "ScoreMatrix.h"
#include "SparseMatrix.h"
#include "GlobalAlign.h"
#include "Tree.h"
#include "Utilities.h"
#include "AlignedFragment.h"
#include "LocalAlign.h"
#include "Block.h"
#include "Consistency.h"
#include "PairAligner.h"
#include "Types.h"
bool verbose = true;
int MINLENGTH = 30; // shortest local alignment
bool enableViterbi = true;
bool enableTransitivity = false;
bool fastaOutput = false;
typedef SparseMatrix *SparseMatrixPtr;
bool GetInteger (char *data, int *val);
void RunEM (ProbModel &hmm, int numFilenames, string *filenames);
void RunLocalAligner (int numFilenames, string *filenames);
//////////////////////////////////////////////////////////////////////
// main program
//////////////////////////////////////////////////////////////////////
int main (int argc, char **argv){
PRECOMPUTE_SCORE_TABLES();
fprintf (stderr, "ProDA version 1.0\n\n");
// usage
if (argc == 1){
fprintf (stderr, "Usage: proda [-L length] [-silent] [-posterior] [-tran] [-fasta] filename(s)\n");
return 0;
}
// find all command-line flags
bool computeEMParams = false;
int numEMreps = 0;
string *filenames = new string[argc];
ASSERT (filenames, "Out of memory.");
int numFilenames = 0;
int i;
for (i = 1; i < argc; i++){
if (argv[i][0] == '-'){
if(!strcmp (argv[i], "-L")){
if( i < argc -1){
if(!GetInteger (argv[++i], &MINLENGTH)){
fprintf(stderr,"ERROR: Invalid integer following option %s :: %s \n",argv[i-1], argv[i]);
exit(1);
}
}
}else if(!strcmp(argv[i],"-posterior")){
enableViterbi = false;
}
else if(!strcmp(argv[i],"-tran")){
enableTransitivity = true;
}
else if(!strcmp(argv[i],"-fasta")){
fastaOutput = true;
}
else if(!strcmp(argv[i],"-silent")){
verbose = false;
}
else {
fprintf (stderr, "Unknown parameter ignored: %s\n", argv[i]);
}
} else {
filenames[numFilenames++] = StrDup (argv[i]);
}
}
fprintf (stderr,"Minimal block length = %d\n\n",MINLENGTH);
// run program
if (computeEMParams){
ProbModel hmm;
for (int i = 0; i < numEMreps; i++)
RunEM (hmm, numFilenames, filenames);
} else {
RunLocalAligner (numFilenames, filenames);
}
// free memory
for (i = 0; i < numFilenames; i++)
delete filenames[i];
delete filenames;
return 0;
}
bool GetInteger (char *data, int *val){
char *endPtr;
long int retVal;
extern int errno;
retVal = strtol (data, &endPtr, 0);
if (retVal == 0 && (errno != 0 || data == endPtr)) return false;
if (errno != 0 && (retVal == LONG_MAX || retVal == LONG_MIN)) return false;
if (retVal < (long) INT_MIN || retVal > (long) INT_MAX) return false;
*val = (int) retVal;
return true;
}
//////////////////////////////////////////////////////////////////////
// Run EM algorithm
//////////////////////////////////////////////////////////////////////
void RunEM (ProbModel &hmm, int numFilenames, string *filenames){
Matrix cts (1, NUM_STATES+1, NUM_STATES+1);
cts.Fill (0);
for (int k = 0; k < numFilenames; k++){
// load alignment
MultiSequence *seqs = new MultiSequence();
ASSERT (seqs, "Out of memory.");
fprintf (stderr, "Loading: %s\n", filenames[k]);
seqs->LoadSequences (filenames[k]);
int n = seqs->GetNumSequences();
ASSERT (n > 0, "No sequences to align!");
// compute sufficient statistics
for (int i = 0; i < n; i++){
for (int j = i+1; j < n; j++){
Matrix *ep = hmm.ComputeExpectedCounts (seqs->GetSequence (i), seqs->GetSequence (j));
Matrix &e = *ep;
for (int a = 0; a < NUM_STATES+1; a++)
for (int b = 0; b < NUM_STATES+1; b++)
cts(0,a,b) += e(0,a,b) / (n*n);
delete ep;
}
}
}
// compute new params
hmm.ComputeParams (&cts);
}
//////////////////////////////////////////////////////////////////////
// Run local alignment procedure
//////////////////////////////////////////////////////////////////////
void RunLocalAligner (int numFilenames, string *filenames){
ProbModel hmm;
int i,j;
MultiSequence *seqs = new MultiSequence();
ASSERT (seqs, "Out of memory.");
// load input sequences
for (i = 0; i < numFilenames; i++){
fprintf (stderr, "Loading: %s\n", filenames[i]);
seqs->LoadSequences (filenames[i]);
}
int n = seqs->GetNumSequences();
ASSERT (n > 0, "No sequences to align!");
AVECT fragments;
// compute pairwise similarities and local aligned fragments
fprintf(stderr,"\nAligning all pairs of sequences. This may take several minutes\n");
for (i = 0; i < n; i++){
for (j = i + 1; j < n; j++){
Sequence seq1 = seqs->GetSequence (i);
Sequence seq2 = seqs->GetSequence (j);
PairAligner pAligner(&hmm,&seq1,&seq2);
if(enableViterbi) pAligner.FastPairAlign(fragments);
else pAligner.PairAlign(fragments);
}
}
char file0[260];
strcpy(file0,filenames[0]);
for(i = strlen(file0)-1; i > 0 && file0[i]!='.'; i--);
if(i > 0) file0[i] = 0;
FILE *fasta;
if(fastaOutput){
strcat(file0,".fasta");
fasta = fopen(file0,"w");
}
strcat(file0,".test");
FILE *output = fopen(file0,"w");
Block *prohibited = NULL;
while (fragments.size() > 0) {
//Form a block
fprintf(stderr,"\nForming block\n");
Block *block = new Block(fragments, seqs, enableTransitivity, prohibited);
prohibited = NULL;
int flag = 1;
fprintf(stderr,"Aligning block\n");
do{
int m = block->size();
SparseMatrix **block_posteriors = new SparseMatrixPtr[m*m];
for (i = 0; i < m*m; i++)
block_posteriors[i] = NULL;
Matrix block_similarity (1, m, m);
block_similarity.Fill (1);
MultiSequence *block_seqs = new MultiSequence();
for (i = 0; i < m; i++){
Fragment fm = (*block)[i];
Sequence *s = new Sequence(seqs->GetSequence(fm.id));
s->Clip(fm.begin, fm.end);
s->SetID(i);
block_seqs->AddSequence(s);
}
for (i = 0; i < m-1; i++){
for (j = i+1; j < m; j++){
ScoreMatrix *p = hmm.Posterior (block_seqs->GetSequence (i), block_seqs->GetSequence (j),MATCH);
Matrix *p2 = new Matrix (*p);
delete p;
float score;
int length;
char *ali = GlobalAlign::ComputeMWTrace(*p2, &score, &length);
delete ali;
block_similarity (0,i,j) = block_similarity (0,j,i) = length >= MINLENGTH ? score / length:0;
block_posteriors[i*m+j] = new SparseMatrix (*p2, 0.01, 0);
delete p2;
block_posteriors[j*m+i] = block_posteriors[i*m+j]->ComputeTranspose();
}
}
// compute expected accuracy tree
Tree tree (block_similarity, *block_seqs, 0.5);
// if not all fragments are related
int mm = tree.GetNumSequences();
if (mm < m && mm >= 2){
block->AdjustAFragmentList(fragments, seqs->GetNumSequences(), &block_similarity, 0.5);
IVECT ids;
tree.GetIDs(ids);
ASSERT(mm == (int)ids.size(), "Wrong tree size\n");
//Form new posterior matrix
SparseMatrix **newPosteriors = new SparseMatrixPtr[mm*mm];
for (i = 0; i < mm*mm; i++)
newPosteriors[i] = NULL;
for (i = 0; i < mm; i++){
for (j = 0; j < mm; j++) if(i != j){
newPosteriors[i*mm+j] = block_posteriors[ids[i]*m+ids[j]];
}
}
int *used = new int[m];
for(i=0; i<m;i++) used[i] = 0;
for(i=0;i<mm;i++) used[ids[i]] = 1;
for (i = 0; i < m; i++)
for (j = 0; j < m; j++)
if (i != j && (used[i]==0 || used[j]==0)) delete block_posteriors[i*m+j];
delete [] block_posteriors;
delete used;
Block *newBlock = new Block();
for (i=0; i<mm;i++){
newBlock->AddFragment((*block)[ids[i]]);
}
delete block;
block = newBlock;
block_posteriors = newPosteriors;
m = mm;
}
if (mm < 2) {
block->AdjustAFragmentList(fragments, seqs->GetNumSequences(), &block_similarity, 0.5);
delete block;
delete block_seqs;
for (i = 0; i < m*m; i++)
if (block_posteriors[i]) delete block_posteriors[i];
delete [] block_posteriors;
break;
}
// probabilistic consistency
for (int c = 0; c < 0; c++){
SparseMatrix **newPosteriors = ProbabilisticConsistency (block_posteriors, m);
for (i = 0; i < m; i++)
for (j = 0; j < m; j++)
if (i != j) delete block_posteriors[i*m+j];
delete [] block_posteriors;
block_posteriors = newPosteriors;
}
MultiSequence *result = tree.ProgressiveAlignment (m, block_posteriors);
result->Sort();
delete block_seqs;
for (i = 0; i < m*m; i++)
if (block_posteriors[i]) delete block_posteriors[i];
delete [] block_posteriors;
int start, end;
result->FindBlock(*block, start, end, int(MINLENGTH*0.9));
if(block->size() == m){
if(end-start+1 >= MINLENGTH*0.9){
block->PrintBlock(stdout,seqs);
block->PrintBlock(output,seqs,1);
result->WriteCLUSTALW(stdout,start, end);
if(fastaOutput)
seqs->WriteFASTA(fasta,block,result,start,end);
}
int deleted = block->AdjustAFragmentList(fragments, seqs->GetNumSequences());
if(deleted) delete block;
else prohibited = block;
flag = 0;
}
delete result;
}while(flag);
}
fclose(output);
if(fastaOutput)
fclose(fasta);
delete seqs;
}
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