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#include "libMUSCLE/muscle.h"
#include "libMUSCLE/msa.h"
#include "libMUSCLE/profile.h"
#include "libMUSCLE/objscore.h"
#include "libMUSCLE/refine.h"
#include "libMUSCLE/tree.h"
#include <vector>
#include <iostream>
namespace muscle {
void MergeBestCols(const SCORE Scores[], const unsigned BestCols[],
unsigned uBestColCount, unsigned uWindowLength, unsigned AnchorCols[],
unsigned *ptruAnchorColCount);
void FindBestColsGrade(const SCORE Score[], unsigned uCount,
double dThreshold, unsigned BestCols[], unsigned *ptruBestColCount);
SCORE ScoreSeqPairLetters(const MSA &msa1, unsigned uSeqIndex1,
const MSA &msa2, unsigned uSeqIndex2, SCORE MatchScore[] )
{
const unsigned uColCount = msa1.GetColCount();
const unsigned uColCount2 = msa2.GetColCount();
if (uColCount != uColCount2)
Quit("ScoreSeqPairLetters, different lengths");
#if TRACE_SEQPAIR
{
Log("\n");
Log("ScoreSeqPairLetters\n");
MSA msaTmp;
msaTmp.SetSize(2, uColCount);
msaTmp.CopySeq(0, msa1, uSeqIndex1);
msaTmp.CopySeq(1, msa2, uSeqIndex2);
msaTmp.LogMe();
}
#endif
SCORE scoreLetters = 0;
SCORE scoreGaps = 0;
bool bGapping1 = false;
bool bGapping2 = false;
unsigned uColStart = 0;
bool bLeftTermGap = false;
for (unsigned uColIndex = 0; uColIndex < uColCount; ++uColIndex)
{
bool bGap1 = msa1.IsGap(uSeqIndex1, uColIndex);
bool bGap2 = msa2.IsGap(uSeqIndex2, uColIndex);
if (!bGap1 || !bGap2)
{
if (bGap1 || bGap2)
bLeftTermGap = true;
uColStart = uColIndex;
break;
}
}
unsigned uColEnd = uColCount - 1;
bool bRightTermGap = false;
for (int iColIndex = (int) uColCount - 1; iColIndex >= 0; --iColIndex)
{
bool bGap1 = msa1.IsGap(uSeqIndex1, iColIndex);
bool bGap2 = msa2.IsGap(uSeqIndex2, iColIndex);
if (!bGap1 || !bGap2)
{
if (bGap1 || bGap2)
bRightTermGap = true;
uColEnd = (unsigned) iColIndex;
break;
}
}
#if TRACE_SEQPAIR
Log("LeftTermGap=%d RightTermGap=%d\n", bLeftTermGap, bRightTermGap);
#endif
for (unsigned uColIndex = uColStart; uColIndex <= uColEnd; ++uColIndex)
{
unsigned uLetter1 = msa1.GetLetterEx(uSeqIndex1, uColIndex);
if (uLetter1 >= g_AlphaSize.get())
continue;
unsigned uLetter2 = msa2.GetLetterEx(uSeqIndex2, uColIndex);
if (uLetter2 >= g_AlphaSize.get())
continue;
SCORE scoreMatch = (*g_ptrScoreMatrix.get())[uLetter1][uLetter2];
scoreLetters += scoreMatch;
if( MatchScore != NULL )
MatchScore[uColIndex] = scoreMatch;
}
return scoreLetters;
}
/* a version of ScoreSeqPairGaps that computes a per-residue score */
SCORE ScoreSeqPairGaps(const MSA &msa1, unsigned uSeqIndex1,
const MSA &msa2, unsigned uSeqIndex2, SCORE MatchScore[] )
{
const unsigned uColCount = msa1.GetColCount();
const unsigned uColCount2 = msa2.GetColCount();
if (uColCount != uColCount2)
Quit("ScoreSeqPairGaps, different lengths");
#if TRACE_SEQPAIR
{
Log("\n");
Log("ScoreSeqPairGaps\n");
MSA msaTmp;
msaTmp.SetSize(2, uColCount);
msaTmp.CopySeq(0, msa1, uSeqIndex1);
msaTmp.CopySeq(1, msa2, uSeqIndex2);
msaTmp.LogMe();
}
#endif
SCORE scoreGaps = 0;
bool bGapping1 = false;
bool bGapping2 = false;
unsigned uColStart = 0;
bool bLeftTermGap = false;
for (unsigned uColIndex = 0; uColIndex < uColCount; ++uColIndex)
{
bool bGap1 = msa1.IsGap(uSeqIndex1, uColIndex);
bool bGap2 = msa2.IsGap(uSeqIndex2, uColIndex);
if (!bGap1 || !bGap2)
{
if (bGap1 || bGap2)
bLeftTermGap = true;
uColStart = uColIndex;
break;
}
}
unsigned uColEnd = uColCount - 1;
bool bRightTermGap = false;
for (int iColIndex = (int) uColCount - 1; iColIndex >= 0; --iColIndex)
{
bool bGap1 = msa1.IsGap(uSeqIndex1, iColIndex);
bool bGap2 = msa2.IsGap(uSeqIndex2, iColIndex);
if (!bGap1 || !bGap2)
{
if (bGap1 || bGap2)
bRightTermGap = true;
uColEnd = (unsigned) iColIndex;
break;
}
}
#if TRACE_SEQPAIR
Log("LeftTermGap=%d RightTermGap=%d\n", bLeftTermGap, bRightTermGap);
#endif
unsigned gap_left_col = 0;
SCORE cur_gap_score = 0;
for (unsigned uColIndex = uColStart; uColIndex <= uColEnd; ++uColIndex)
{
bool bGap1 = msa1.IsGap(uSeqIndex1, uColIndex);
bool bGap2 = msa2.IsGap(uSeqIndex2, uColIndex);
if (bGap1 && bGap2)
continue;
if (bGap1)
{
if (!bGapping1)
{
#if TRACE_SEQPAIR
Log("Gap open seq 1 col %d\n", uColIndex);
#endif
gap_left_col = uColIndex;
if (uColIndex == uColStart)
{
scoreGaps += TermGapScore(true);
cur_gap_score += TermGapScore(true);
}else{
scoreGaps += g_scoreGapOpen.get();
cur_gap_score += g_scoreGapOpen.get();
}
bGapping1 = true;
}
else
{
scoreGaps += g_scoreGapExtend.get();
cur_gap_score += g_scoreGapExtend.get();
}
continue;
}
else if (bGap2)
{
if (!bGapping2)
{
#if TRACE_SEQPAIR
Log("Gap open seq 2 col %d\n", uColIndex);
#endif
gap_left_col = uColIndex;
if (uColIndex == uColStart)
{
scoreGaps += TermGapScore(true);
cur_gap_score += TermGapScore(true);
}else{
scoreGaps += g_scoreGapOpen.get();
cur_gap_score += g_scoreGapOpen.get();
}
bGapping2 = true;
}
else
{
scoreGaps += g_scoreGapExtend.get();
cur_gap_score += g_scoreGapExtend.get();
}
continue;
}
if( MatchScore != NULL && (bGapping1 || bGapping2) )
{
// spread the total gap penalty evenly across all columns
SCORE per_site_penalty = cur_gap_score / (uColIndex-gap_left_col);
for( unsigned uGapIndex = gap_left_col; uGapIndex < uColIndex; ++uGapIndex )
{
MatchScore[uGapIndex] = per_site_penalty;
}
gap_left_col = uInsane;
cur_gap_score = 0;
}
bGapping1 = false;
bGapping2 = false;
}
if (bGapping1 || bGapping2)
{
scoreGaps -= g_scoreGapOpen.get();
scoreGaps += TermGapScore(true);
cur_gap_score -= g_scoreGapOpen.get();
cur_gap_score += TermGapScore(true);
if( MatchScore != NULL )
{
// spread the total gap penalty evenly across all columns
SCORE per_site_penalty = cur_gap_score / (uColCount-gap_left_col);
for( unsigned uGapIndex = gap_left_col; uGapIndex < uColCount; ++uGapIndex )
{
MatchScore[uGapIndex] = per_site_penalty;
}
}
}
return scoreGaps;
}
// this is a version of the profile x profile score that computes
// a per-site score suitable for use with anchoring heuristics
SCORE LetterObjScoreXP(const MSA &msa1, const MSA &msa2, SCORE MatchScore[])
{
const unsigned uColCount1 = msa1.GetColCount();
const unsigned uColCount2 = msa2.GetColCount();
if (uColCount1 != uColCount2)
Quit("ObjScoreXP, alignment lengths differ %u %u", uColCount1, uColCount2);
const unsigned uSeqCount1 = msa1.GetSeqCount();
const unsigned uSeqCount2 = msa2.GetSeqCount();
#if TRACE
Log(" Score Weight Weight Total\n");
Log("---------- ------ ------ ----------\n");
#endif
SCORE* mmScore = NULL;
SCORE* ggScore = NULL;
if( MatchScore != NULL )
{
mmScore = new SCORE[uColCount1];
ggScore = new SCORE[uColCount1];
memset( MatchScore, 0, sizeof(SCORE)*uColCount1 );
}
SCORE scoreTotal = 0;
unsigned uPairCount = 0;
for (unsigned uSeqIndex1 = 0; uSeqIndex1 < uSeqCount1; ++uSeqIndex1)
{
const WEIGHT w1 = msa1.GetSeqWeight(uSeqIndex1);
for (unsigned uSeqIndex2 = 0; uSeqIndex2 < uSeqCount2; ++uSeqIndex2)
{
if( mmScore != NULL )
memset( mmScore, 0, sizeof(SCORE)*uColCount1 );
if( ggScore != NULL )
memset( ggScore, 0, sizeof(SCORE)*uColCount1 );
const WEIGHT w2 = msa2.GetSeqWeight(uSeqIndex2);
const WEIGHT w = w1*w2;
SCORE scoreLetters = ScoreSeqPairLetters(msa1, uSeqIndex1, msa2, uSeqIndex2, mmScore);
SCORE scoreGaps = ScoreSeqPairGaps(msa1, uSeqIndex1, msa2, uSeqIndex2, ggScore);
SCORE scorePair = scoreLetters + scoreGaps;
scoreTotal += w*scorePair;
++uPairCount;
if( MatchScore != NULL )
for( unsigned uColIndex = 0; uColIndex < uColCount1; ++uColIndex )
MatchScore[uColIndex] += w*(mmScore[uColIndex]+ggScore[uColIndex]);
#if TRACE
Log("%10.2f %6.3f %6.3f %10.2f >%s >%s\n",
scorePair,
w1,
w2,
scorePair*w1*w2,
msa1.GetSeqName(uSeqIndex1),
msa2.GetSeqName(uSeqIndex2));
#endif
}
}
if (0 == uPairCount)
Quit("0 == uPairCount");
#if TRACE
Log("msa1=\n");
msa1.LogMe();
Log("msa2=\n");
msa2.LogMe();
Log("XP=%g\n", scoreTotal);
#endif
// return scoreTotal / uPairCount;
if( mmScore != NULL )
delete[] mmScore;
if( ggScore != NULL )
delete[] ggScore;
return scoreTotal;
}
// Best col only if all following criteria satisfied:
// (1) Score >= min
// (2) Smoothed score >= min
static void FindBestColsComboPP(unsigned uColCount, const SCORE Score[],
const SCORE SmoothScore[], double dMinScore, double dMinSmoothScore,
unsigned BestCols[], unsigned *ptruBestColCount)
{
unsigned uBestColCount = 0;
for (unsigned uIndex = 0; uIndex < uColCount; ++uIndex)
{
if (Score[uIndex] < dMinScore)
continue;
if (SmoothScore[uIndex] < dMinSmoothScore)
continue;
BestCols[uBestColCount] = uIndex;
++uBestColCount;
}
*ptruBestColCount = uBestColCount;
}
void FindAnchorColsPP(const MSA &msa1, const MSA &msa2, unsigned AnchorCols[],
unsigned *ptruAnchorColCount)
{
const unsigned uColCount = msa1.GetColCount();
if( uColCount != msa2.GetColCount() )
{
*ptruAnchorColCount = 0;
return; // the profiles must have equal length to find anchor cols
}
SCORE *MatchScore = new SCORE[uColCount];
SCORE *SmoothScore = new SCORE[uColCount];
unsigned *BestCols = new unsigned[uColCount];
LetterObjScoreXP(msa1, msa2, MatchScore);
g_uSmoothWindowLength.get() = 21; // this is better for DNA
g_uAnchorSpacing.get() = 96;
WindowSmooth(MatchScore, uColCount, g_uSmoothWindowLength.get(), SmoothScore,
g_dSmoothScoreCeil.get());
unsigned uBestColCount;
// FindBestColsGrade(SmoothScore,uColCount,.85,BestCols,&uBestColCount);
FindBestColsComboPP(uColCount, MatchScore, SmoothScore, g_dMinBestColScore.get(), g_dMinSmoothScore.get(),
BestCols, &uBestColCount);
/*
std::cerr << "found " << uBestColCount << " anchor cols:\n";
for( size_t colI = 0; colI < uBestColCount; colI++ )
{
if( colI > 0 )
std::cerr << ", ";
std::cerr << BestCols[colI];
}
std::cerr << std::endl;
*/
#if TRACE
ListBestCols(msa, MatchScore, SmoothScore, BestCols, uBestColCount);
#endif
MergeBestCols(MatchScore, BestCols, uBestColCount, g_uAnchorSpacing.get(), AnchorCols,
ptruAnchorColCount);
/*
std::cerr << "\n\nafter merging, have " << *ptruAnchorColCount << " anchor cols:\n";
for( size_t colI = 0; colI < *ptruAnchorColCount; colI++ )
{
if( colI > 0 )
std::cerr << ", ";
std::cerr << AnchorCols[colI];
}
std::cerr << std::endl;
*/
delete[] MatchScore;
delete[] SmoothScore;
delete[] BestCols;
}
void StripGapColumns( MSA& msa )
{
unsigned uCurCol = 0;
for( unsigned uColIndex = 0; uColIndex < msa.GetColCount(); uColIndex++ )
{
if( !msa.IsGapColumn(uColIndex) )
{
for( unsigned uGapSeq = 0; uGapSeq < msa.GetSeqCount(); uGapSeq++ )
{
msa.SetChar(uGapSeq, uCurCol, msa.GetChar(uGapSeq,uColIndex));
}
uCurCol++;
}
}
msa.DeleteColumns(uCurCol, msa.GetColCount()-uCurCol);
}
void PrepareMSAforScoring( MSA& msa )
{
Tree tree;
const unsigned uSeqCount = msa.GetSeqCount();
for (unsigned uSeqIndex = 0; uSeqIndex < uSeqCount; ++uSeqIndex)
msa.SetSeqId(uSeqIndex, uSeqIndex);
TreeFromMSA(msa, tree, g_Cluster2.get(), g_Distance2.get(), g_Root1.get());
SetMuscleTree(tree);
SetMSAWeightsMuscle(msa);
}
// Return true if any changes made
void AnchoredProfileProfile(MSA &msa1, MSA &msa2, MSA &msaOut)
{
const unsigned uColCountIn = msa1.GetColCount();
const unsigned uSeqCountIn = msa1.GetSeqCount() + msa2.GetSeqCount();
unsigned *AnchorCols = new unsigned[uColCountIn];
unsigned uAnchorColCount;
PrepareMSAforScoring(msa1);
PrepareMSAforScoring(msa2);
FindAnchorColsPP(msa1, msa2, AnchorCols, &uAnchorColCount);
const unsigned uRangeCount = uAnchorColCount + 1;
Range *Ranges = new Range[uRangeCount];
#if TRACE
Log("%u ranges\n", uRangeCount);
#endif
ColsToRanges(AnchorCols, uAnchorColCount, uColCountIn, Ranges);
ListVertSavings(uColCountIn, uAnchorColCount, Ranges, uRangeCount);
#if TRACE
{
Log("Anchor cols: ");
for (unsigned i = 0; i < uAnchorColCount; ++i)
Log(" %u", AnchorCols[i]);
Log("\n");
Log("Ranges:\n");
for (unsigned i = 0; i < uRangeCount; ++i)
Log("%4u - %4u\n", Ranges[i].m_uBestColLeft, Ranges[i].m_uBestColRight);
}
#endif
delete[] AnchorCols;
msaOut.SetSize(uSeqCountIn, 0);
for (unsigned uSeqIndex = 0; uSeqIndex < uSeqCountIn; ++uSeqIndex)
{
const char *ptrName;
unsigned uId;
if( uSeqIndex < msa1.GetSeqCount() )
{
msa1.SetSeqId(uSeqIndex, uSeqIndex);
ptrName = msa1.GetSeqName(uSeqIndex);
}
else
{
msa2.SetSeqId(uSeqIndex-msa1.GetSeqCount(), uSeqIndex);
ptrName = msa2.GetSeqName(uSeqIndex-msa1.GetSeqCount());
}
msaOut.SetSeqName(uSeqIndex, ptrName);
msaOut.SetSeqId(uSeqIndex, uSeqIndex);
}
for (unsigned uRangeIndex = 0; uRangeIndex < uRangeCount; ++uRangeIndex)
{
MSA msaRange1;
MSA msaRange2;
MSA msaRangeOut;
const Range &r = Ranges[uRangeIndex];
const unsigned uFromColIndex = r.m_uBestColLeft;
const unsigned uRangeColCount = r.m_uBestColRight - uFromColIndex;
if (0 == uRangeColCount)
continue;
/* else if (1 == uRangeColCount)
{
MSAFromColRange(msaIn, uFromColIndex, 1, msaRange);
MSAAppend(msaOut, msaRange);
continue;
}
*/
MSAFromColRange(msa1, uFromColIndex, uRangeColCount, msaRange1);
MSAFromColRange(msa2, uFromColIndex, uRangeColCount, msaRange2);
StripGapColumns(msaRange1);
StripGapColumns(msaRange2);
#if TRACE
Log("\n-------------\n");
Log("Range %u - %u count=%u\n", r.m_uBestColLeft, r.m_uBestColRight, uRangeColCount);
Log("Before:\n");
msaRange1.LogMe();
msaRange2.LogMe();
#endif
ProfileProfile(msaRange1, msaRange2, msaRangeOut);
#if TRACE
Log("After:\n");
msaRangeOut.LogMe();
#endif
for (unsigned uSeqIndex = 0; uSeqIndex < uSeqCountIn; ++uSeqIndex)
msaRangeOut.SetSeqId(uSeqIndex, uSeqIndex);
MSAAppend(msaOut, msaRangeOut);
#if TRACE
Log("msaOut after Cat:\n");
msaOut.LogMe();
#endif
}
delete[] Ranges;
}
}
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