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RefineBreakpoint.h
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469 lines (423 loc) · 12.3 KB
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#ifndef _REFINE_Breakpoint_H_
#define _REFINE_Breakpoint_H_
#include <vector>
#include "AlignmentBlock.h"
void PrependBlocks(vector<Block> &src, vector<Block> &dest) {
if (src.size() == 0) { return;}
if (dest.size() == 0) { dest = src; return;}
int last=src.size()-1;
// If the last match is a gapless extension, that can mess up some cigar parsing.
if (src[last].tPos + src[last].length == dest[0].tPos and
src[last].qPos + src[last].length == dest[0].qPos) {
dest[0].tPos -= src[last].length;
dest[0].qPos -= src[last].length;
dest[0].length += src[last].length;
src.resize(last);
}
dest.resize(dest.size()+ src.size());
for (int i=dest.size(); i > src.size(); i--) {
dest[i-1] = dest[i-src.size()-1];
}
for (int i=0; i < src.size(); i++) {
dest[i] = src[i];
}
}
void AppendBlocks(vector<Block> &src, vector<Block> &dest) {
if (src.size() == 0) { return;}
if (dest.size() == 0) { dest = src; return;}
int last=dest.size()-1;
// If the last match is a gapless extension, that can mess up some cigar parsing.
int srcStart=0;
if (dest[last].tPos + dest[last].length == src[0].tPos and
dest[last].qPos + dest[last].length == src[0].qPos) {
dest[last].length += src[0].length;
srcStart=1;
}
int destEnd=dest.size();
dest.resize(dest.size() + src.size() - srcStart);
for (int i=srcStart; i < src.size(); i++) {
dest[destEnd] = src[i];
destEnd++;
}
}
void PathToBlocks(vector<int> &path, vector<Block> &blocks) {
int i=0;
int left=1,down=2,diag=3;
int q=0, t=0;
while (i < path.size() and path[i] != diag and (path[i] == left or path[i] == down)) {
if (path[i] == left) { q++;}
if (path[i] == down) { t++;}
i++;
}
while (i < path.size()) {
int ml=0;
int qs=q;
int ts=t;
while (i < path.size() and path[i] == diag) {
ml++;
q++;
t++;
i++;
}
while (i < path.size() and (path[i] == left or path[i] == down)) {
if (path[i] == left) { q++;}
if (path[i] == down) { t++;}
i++;
}
int match=min(q-qs, t-ts);
if (match > 0) {
blocks.push_back(Block(qs,ts,match));
}
}
}
void PrintMat(vector<int> &mat, int r) {
for (int i=0; i < mat.size(); i++) {
cout << "\t" << mat[i];
if ((i+1)%r == 0) { cout << endl;}
}
}
void TraceBack(vector<int> &path, int q, int t, int r, vector<int> &tb) {
q++;
t++;
int i=t*r+q;
int left=1;
int down=2;
int diag=3;
while (q >0 or t > 0) {
if (path[i] == diag) {
q--;
t--;
tb.push_back(diag);
}
if (path[i] == left) {
q--;
tb.push_back(left);
}
if (path[i] == down) {
t--;
tb.push_back(down);
}
i=(t)*r+(q);
}
reverse(tb.begin(), tb.end());
}
void StoreQScoreVect(vector<int> &score, vector<int> &path, int q, int t, int r, vector<int> &qv, vector<int> &index) {
qv.resize(r-1);
index.resize(r-1);
fill(qv.begin(), qv.end(), 0);
int i=(t+1)*r+q+1;
int left=1;
int down=2;
int diag=3;
// index into matrix is up by 1
q++;
t++;
while (i > 0) {
if (path[i] == diag or path[i] == left) {
assert(q > 0);
qv[q-1] = score[i];
index[q-1] = i;
}
if (path[i] == diag) {
q--;
t--;
}
if (path[i] == left) {
q--;
}
if (path[i] == down) {
t--;
}
i=(t)*r+(q);
}
}
void RSdp(string &q, string &t, vector<int> &path, vector<int> &score,
int mat, int mis, int indel) {
path.resize((q.size()+1)*(t.size()+1), -1);
score.resize((q.size()+1)*(t.size()+1),0);
int qs=q.size();
int ts=t.size();
int left=1;
int down=2;
int diag=3;
int row=qs+1;
for (int i=1; i < qs+1;i++) {
path[i] = left;
score[i] = score[i-1] + indel;
}
for (int i=1; i < ts+1; i++) {
path[row*i] = down;
score[i*row] = score[(i-1)*row] + indel;
}
for (int i=0; i < ts; i++) {
for (int j=0; j < qs; j++) {
int diagScore = score[i*row+j];
if (q[j] == t[i]) {
diagScore += mat;
}
else {
diagScore += mis;
}
int leftScore = score[(i+1)*row + j] + indel;
int downScore = score[i*row + (j+1)] + indel;
int maxScore =max(diagScore, max(leftScore, downScore));
score[(i+1)*row+(j+1)] = maxScore;
if (maxScore == diagScore) {
path[(i+1)*row+(j+1)] = diag;
}
else if (maxScore == leftScore) {
path[(i+1)*row+(j+1)] = left;
}
else {
path[(i+1)*row+(j+1)] = down;
}
}
}
//
// No need for trace back here.
//
}
int FindMax(vector<int> &score, int row, int &q, int &t) {
if (score.size() == 0) {
q=t=0;
return 0;
}
vector<int>::iterator itr = max_element(score.begin(), score.end());
int index=itr-score.begin();
t=index/row-1;
q=index%row-1;
return score[index];
}
void RefineBreakpoint(Read &read,
Genome &genome,
Alignment &leftAln,
Alignment &rightAln,
const Options &opts) {
int lqs=0, lqe=0, lts=0, lte=0;
int rqs=0, rqe=0, rts=0, rte=0;
lqs=leftAln.GetQStart();
lqe=leftAln.GetQEnd();
lts=leftAln.GetTStart();
lte=leftAln.GetTEnd();
int flqs=0, flqe=0, rlqs=0, rlqe=0;
if (leftAln.strand == 0) {
flqs=lqs;
flqe=lqe;
}
else {
flqs = read.length - lqe;
flqe = read.length - lqs;
}
rqs=rightAln.GetQStart();
rqe=rightAln.GetQEnd();
rts=rightAln.GetTStart();
rte=rightAln.GetTEnd();
int frqs=0, frqe=0;
if (rightAln.strand == 0) {
frqs=rqs;
frqe=rqe;
}
else {
frqs = read.length - rqe;
frqe = read.length - rqs;
}
/*
cerr << "LEFT\t" << (int) leftAln.strand << "\t" << leftAln.blocks.size() << "\t" << flqs << "\t" << flqe << "\t"
<< "RIGHT\t" << (int) rightAln.strand << "\t" << rightAln.blocks.size() << "\t" << frqs << "\t" << frqe << endl;
*/
int MAX_GAP=500;
if (frqs > flqe and frqs - flqe < MAX_GAP) {
//
// The two endpoints are close enough to attempt to refine the breakpoint.
//
// For now just do standard dp, speed up later if need be.
int span = frqs - flqe;
//
// Determine spans that are refined for left.
//
string lqString, ltString;
char *tChrom=genome.seqs[leftAln.chromIndex];
bool lPrefixExtend=false;
int lqExtStart, lqExtEnd;
int ltExtStart, ltExtEnd;
if (leftAln.strand == 0) {
//
// Missed segment is at right side of left aln
//
lqExtStart = lqe;
lqExtEnd = lqe+span;
lqString = string(leftAln.read + lqe, span);
//
// Left align is forward strand. Refining will go from the end of alignment on
//
ltExtStart = leftAln.GetTEnd();
int tSpan = min(genome.lengths[leftAln.chromIndex]-leftAln.GetTEnd(), span);
ltExtEnd = ltExtStart+tSpan;
ltString = string(tChrom+ltExtStart, tSpan);
}
else {
assert(lqs-span > 0);
// missed segment is at left side of rev strand
lqExtStart = lqs-span;
lqExtEnd = lqs;
lqString = string(leftAln.read + lqExtStart, span);
//
// Left align is reverse strand. The gap goes forward in the read, which means it exends back in target
ltExtEnd = leftAln.GetTStart();
ltExtStart = max(0,ltExtEnd-span);
ltString = string(tChrom+ltExtStart, ltExtEnd-ltExtStart);
lPrefixExtend=true;
reverse(lqString.begin(), lqString.end());
reverse(ltString.begin(), ltString.end());
}
vector<int> lPath, lScore, rPath, rScore;
int mat=2;
int mis=-2;
int gap=-4;
/*
cerr << "query" << endl;
cerr << lqString << endl;
cerr << "target" << endl;
cerr << ltString << endl;
*/
RSdp(lqString, ltString, lPath, lScore, mat,mis,gap);
//
// Right-hand side logic is the reverse.
//
string rqString, rtString;
string rqStringCopy, rtStringCopy;
char *rtChrom=genome.seqs[rightAln.chromIndex];
bool rPrefixExtend=false;
int rqExtStart, rqExtEnd;
int rtExtStart, rtExtEnd;
if (rightAln.strand == 0) {
//
rqExtStart = rqs - span;
rqExtEnd = rqs;
rqString=string(rightAln.read + rqExtStart, span);
int rtSpan = min(rightAln.GetTStart(), span);
rtExtStart = rightAln.GetTStart() - rtSpan;
rtExtEnd = rightAln.GetTStart();
rtString = string(rtChrom+rtExtStart, rtSpan);
reverse(rqString.begin(), rqString.end());
reverse(rtString.begin(), rtString.end());
rPrefixExtend=true;
}
else {
rqExtStart = rightAln.GetQEnd();
rqExtEnd = rqExtStart+span;
assert(rqExtStart+span <= read.length);
rqString = string(rightAln.read + rqExtStart, span);
rtExtStart = rightAln.GetTEnd();
int tSpan = span;
if (rtExtStart+span >= genome.lengths[rightAln.chromIndex]) {
tSpan = genome.lengths[rightAln.chromIndex] - rtExtStart;
}
rtExtEnd = rtExtStart+tSpan;
rtString = string(rtChrom+rtExtStart, tSpan);
}
/*
cerr << "rquery" << endl;
cerr << rqString << endl;
cerr << "rtarget" << endl;
cerr << rtString << endl;
*/
RSdp(rqString, rtString, rPath, rScore, mat,mis,gap);
int mls, mlq, mlt, mrs, mrq, mrt;
mls=FindMax(lScore, span+1, mlq, mlt);
mrs=FindMax(rScore, span+1, mrq, mrt);
// cerr << "left " << mlq << "\t" << mlt << "\t" << mls << "\tright\t" << mrq << "\t" << mrt << "\t" << mrs << endl;
// Now to merge the two results.
//
// Case 1, the local alignments do not overlap
int maxLIndex=0;
int maxRIndex=0;
if (mlq < span - mrq ) {
// cerr << "Alignments do not overlap " << endl;
}
else {
// cerr << "Alignments do overlap. Optimize" << endl;
vector<int> lqScores, rqScores, lqIndex, rqIndex;
StoreQScoreVect(lScore, lPath, mlq, mlt, span+1, lqScores, lqIndex);
StoreQScoreVect(rScore, rPath, mrq, mrt, span+1, rqScores, rqIndex);
assert(lqScores.size() == rqScores.size());
int maxScore=0;
for (int i=0; i < lqScores.size(); i++ ) {
if (lqScores[i] + rqScores[lqScores.size()-i-1] > maxScore) {
maxScore = lqScores[i] + rqScores[lqScores.size()-i-1];
maxLIndex=i;
maxRIndex=lqScores.size()-i-1;
}
}
int maxLI=lqIndex[maxLIndex];
int maxRI=rqIndex[maxRIndex];
mlq=maxLIndex;
mlt=maxLI/(span+1)-1;
mrq=maxRIndex;
mrt=maxRI/(span+1)-1;
}
vector<int> ltb, rtb;
TraceBack(lPath, mlq, mlt, span+1, ltb);
TraceBack(rPath, mrq, mrt, span+1, rtb);
/*
for (int i=0;i<ltb.size(); i++){ cerr << ltb[i]; }
cerr << endl;
for (int i=0;i<rtb.size(); i++){ cerr << rtb[i]; }
cerr << endl;
*/
//
// Now append these to the alignments.
//
vector<Block> lBlocks, rBlocks;
int lqBlockStart=-1, ltBlockStart=-1;
if (lPrefixExtend == true) {
reverse(ltb.begin(), ltb.end());
reverse(lqString.begin(), lqString.end());
reverse(ltString.begin(), ltString.end());
int qs=lqExtEnd-1;
int ts=ltExtEnd-1;
for (int i=0; i < ltb.size(); i++) {
if (ltb[i] == 3) { qs--; ts--;}
if (ltb[i] == 2) { ts--;}
if (ltb[i] == 1) { qs--;}
}
lqBlockStart=leftAln.GetQStart()-mlq-1;
ltBlockStart=leftAln.GetTStart()-mlt-1;
// mlq=lqString.size() - mlq - 1;
// mlt=ltString.size() - mlt - 1;
}
else {
lqBlockStart=leftAln.GetQEnd();
ltBlockStart=leftAln.GetTEnd();
}
PathToBlocks(ltb, lBlocks);
for (int i=0; i < lBlocks.size(); i++) { lBlocks[i].qPos+=lqBlockStart; lBlocks[i].tPos+=ltBlockStart;}
if (lPrefixExtend) {
PrependBlocks(lBlocks, leftAln.blocks);
}
else {
AppendBlocks(lBlocks, leftAln.blocks);
}
int rqBlockStart=-1, rtBlockStart=-1;
if (rPrefixExtend == true) {
reverse(rtb.begin(), rtb.end());
rqBlockStart=rightAln.GetQStart()-mrq-1;
rtBlockStart=rightAln.GetTStart()-mrt-1;
// mrq=rqString.size() - mrq - 1;
// mrt=rtString.size() - mrt - 1;
}
else {
rqBlockStart = rightAln.GetQEnd();
rtBlockStart = rightAln.GetTEnd();
}
PathToBlocks(rtb, rBlocks);
for (int i=0; i < rBlocks.size(); i++) { rBlocks[i].qPos+=rqBlockStart; rBlocks[i].tPos+=rtBlockStart;}
if (rPrefixExtend) {
PrependBlocks(rBlocks, rightAln.blocks);
}
else {
AppendBlocks(rBlocks, rightAln.blocks);
}
}
}
#endif