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package aligner;
import dna.AminoAcid;
import shared.KillSwitch;
import shared.Tools;
/**
* Based on MSA9PBA, but reduced to a single matrix. */
public final class SingleStateAlignerFlat implements Aligner {
public SingleStateAlignerFlat(){}
private void prefillTopRow(){
final int[] header=packed[0];
final int qlen=rows;
for(int i=0; i<=columns; i++){
int x=columns-i+1;
int qbases=qlen-x;
//Minimal points to prefer a leftmost alignment
header[i]=qbases<=0 ? 0 : ((-qbases)<<STARTOFFSET);
//Forces consumption of query, but does not allow for insertions...
// header[i]=qbases<=0 ? 0 : calcDelScoreOffset(qbases);
}
}
private void prefillLeftColumnStartingAt(int i){
packed[0][0]=MODE_MATCH;
i=Tools.max(1, i);
for(int score=MODE_INS+(POINTSoff_INS*i); i<=maxRows; i++){//Fill column 0 with insertions
score+=POINTSoff_INS;
packed[i][0]=score;
}
}
// private void clearInner(){//NotmaxRows needed
// for(int i=1; i<=maxRows; i++){
// for(int j=1; j<=maxColumns; j++){
// packed[i][j]=0;
// }
// }
// }
//
// private void clearAll(){//NotmaxRows needed
// for(int i=0; i<=maxRows; i++){
// for(int j=0; j<=maxColumns; j++){
// packed[i][j]=0;
// }
// }
// }
private void initialize(int rows_, int columns_){
rows=rows_;
columns=columns_;
if(rows<=maxRows && columns<=maxColumns){
prefillTopRow();
// prefillLeftColumn();
return;
}
final int maxRows0=maxRows;
final int maxColumns0=maxColumns;
final int[][] packed0=packed;
//Monotonic increase
maxRows=Tools.max(maxRows, rows+10);
maxColumns=Tools.max(maxColumns, columns+10);
if(packed==null || maxColumns>maxColumns0){//Make a new matrix
packed=KillSwitch.allocInt2D(maxRows+1, maxColumns+1);
prefillLeftColumnStartingAt(1);
}else{//Copy old rows
assert(maxRows0>0 && maxColumns0>0);
assert(maxRows>maxRows0 && maxColumns<=maxColumns0);
packed=KillSwitch.allocInt2D(maxRows+1);
for(int i=0; i<packed.length; i++){
if(i<packed0.length){
packed[i]=packed0[i];
}else{
packed[i]=KillSwitch.allocInt1D(maxColumns+1);
}
}
//Fill column 0 with insertions
prefillLeftColumnStartingAt(maxRows0);
}
prefillTopRow();
}
/** return new int[] {rows, maxCol, maxState, maxScore, maxStart};
* Will not fill areas that cannot match minScore */
@Override
public final int[] fillLimited(byte[] read, byte[] ref, int refStartLoc, int refEndLoc, int minScore){
return fillUnlimited(read, ref, refStartLoc, refEndLoc, minScore);
}
@Override
public final int[] fillUnlimited(byte[] read, byte[] ref, int refStartLoc, int refEndLoc){
return fillUnlimited(read, ref, refStartLoc, refEndLoc, -999999);
}
/** return new int[] {rows, maxCol, maxState, maxScore, maxStart};
* Min score is optional */
@Override
public final int[] fillUnlimited(byte[] read, byte[] ref, int refStartLoc, int refEndLoc, int minScore){
initialize(read.length, refEndLoc-refStartLoc+1);
//temporary, for finding a bug
if(rows>maxRows || columns>maxColumns){
throw new RuntimeException("rows="+rows+", maxRows="+maxRows+", cols="+columns+", maxCols="+maxColumns+"\n"+new String(read)+"\n");
}
assert(rows<=maxRows) : "Check that values are in-bounds before calling this function: "+rows+", "+maxRows;
assert(columns<=maxColumns) : "Check that values are in-bounds before calling this function: "+columns+", "+maxColumns;
assert(refStartLoc>=0) : "Check that values are in-bounds before calling this function: "+refStartLoc;
assert(refEndLoc<ref.length) : "Check that values are in-bounds before calling this function: "+refEndLoc+", "+ref.length;
final int refOffset=refStartLoc-1;
for(int row=1; row<=rows; row++){
final byte qBase=read[row-1];
for(int col=1; col<=columns; col++){
final byte rBase=ref[refOffset+col];
final boolean match=(qBase==rBase);
final boolean defined=(qBase!='N' && rBase!='N');
final int valueFromDiag=packed[row-1][col-1];
final int valueFromDel=packed[row][col-1];
final int valueFromIns=packed[row-1][col];
// final int stateFromDiag=valueFromDiag&MODEMASK;
final int scoreFromDiag=valueFromDiag&HIGHMASK;
// final int stateFromDel=valueFromDel&MODEMASK;
final int scoreFromDel=valueFromDel&HIGHMASK;
// final int stateFromIns=valueFromIns&MODEMASK;
final int scoreFromIns=valueFromIns&HIGHMASK;
// final boolean prevMatch=stateFromDiag==MODE_MATCH;
// final boolean prevSub=stateFromDiag==MODE_SUB;
// final boolean prevDel=stateFromDel==MODE_DEL;
// final boolean prevIns=stateFromIns==MODE_INS;
//Old conditional code, replaced by faster arrays
// final int diagScoreM=MODE_MATCH|(prevMatch ? POINTSoff_MATCH2 : POINTSoff_MATCH);
// final int diagScoreS=MODE_SUB|(prevSub ? POINTSoff_SUB2 : POINTSoff_SUB);
// final int delScore=scoreFromDel+(prevDel ? POINTSoff_DEL2 : POINTSoff_DEL)|MODE_DEL;
// final int insScore=scoreFromIns+(prevIns ? POINTSoff_INS2 : POINTSoff_INS)|MODE_INS;
final int diagScoreM=POINTSoff_MATCH|MODE_MATCH;
final int diagScoreS=POINTSoff_SUB|MODE_SUB;
final int delScore=scoreFromDel+POINTSoff_DEL|MODE_DEL;
final int insScore=scoreFromIns+POINTSoff_INS|MODE_INS;
int diagScore=(match ? diagScoreM : diagScoreS);
diagScore=scoreFromDiag+(defined ? diagScore : POINTSoff_NOREF_MODE_SUB);
int score=diagScore>=delScore ? diagScore : delScore;
score=score>=insScore ? score : insScore;
packed[row][col]=score;
}
// iterationsUnlimited+=columns;
}
int maxCol=-1;
int maxState=-1;
int maxStart=-1;
int maxScore=Integer.MIN_VALUE;
for(int col=1; col<=columns; col++){
int x=packed[rows][col];
if((x&SCOREMASK)>maxScore){
maxScore=x;
maxCol=col;
maxState=x&MODEMASK;
maxStart=x&STARTMASK;
}
}
maxScore>>=SCOREOFFSET;
// System.err.println("Returning "+rows+", "+maxCol+", "+maxState+", "+maxScore+"; minScore="+minScore);
return maxScore<minScore ? null : new int[] {rows, maxCol, maxState, maxScore, maxStart};
}
/** Generates the match string */
@Override
public final byte[] traceback(byte[] query, byte[] ref, int refStartLoc, int refEndLoc, int row, int col, int state){
// assert(false);
assert(refStartLoc<=refEndLoc) : refStartLoc+", "+refEndLoc;
assert(row==rows);
byte[] out=new byte[row+col-1]; //TODO if an out of bound crash occurs, try removing the "-1".
int outPos=0;
// assert(state==(packed[row][col]&MODEMASK));
while(row>0 && col>0){
byte q=query[row-1];
byte r=ref[refStartLoc+col-1];
boolean defined=(AminoAcid.isFullyDefined(q) && AminoAcid.isFullyDefined(r));
state=(packed[row][col]&MODEMASK);
if(state==MODE_MATCH){
col--;
row--;
out[outPos]=defined ? (byte)'m' : (byte)'N';
}else if(state==MODE_SUB){
col--;
row--;
out[outPos]=defined ? (byte)'S' : (byte)'N';
}else if(state==MODE_N){
col--;
row--;
out[outPos]='N';
}else if(state==MODE_DEL){
col--;
out[outPos]='D';
}else if(state==MODE_INS){
row--;
// out[outPos]='I';
if(col>=0 && col<columns){
out[outPos]='I';
}else{
out[outPos]='C';
col--;
}
}else{
assert(false) : state;
}
outPos++;
}
assert(row==0 || col==0);
if(col!=row){//Not sure what this is doing
while(row>0){
out[outPos]='C';
outPos++;
row--;
col--;
}
if(col>0){
//do nothing
}
}
//Shrink and reverse the string
byte[] out2=new byte[outPos];
for(int i=0; i<outPos; i++){
out2[i]=out[outPos-i-1];
}
out=null;
return out2;
}
@Override
/** Generates identity;
* fills 'extra' with {match, sub, del, ins, N, clip} if present */
public float tracebackIdentity(byte[] query, byte[] ref, int refStartLoc, int refEndLoc, int row, int col, int state, int[] extra){
// assert(false);
assert(refStartLoc<=refEndLoc) : refStartLoc+", "+refEndLoc;
assert(row==rows);
// assert(state==(packed[row][col]&MODEMASK));
int match=0, sub=0, del=0, ins=0, noref=0, clip=0;
while(row>0 && col>0){
byte q=query[row-1];
byte r=ref[refStartLoc+col-1];
boolean defined=(AminoAcid.isFullyDefined(q) && AminoAcid.isFullyDefined(r));
state=(packed[row][col]&MODEMASK);
if(state==MODE_MATCH){
col--;
row--;
match+=(defined ? 1 : 0);
noref+=(defined ? 0 : 1);
}else if(state==MODE_SUB){
col--;
row--;
sub+=(defined ? 1 : 0);
noref+=(defined ? 0 : 1);
}else if(state==MODE_N){//Can't currently happen
col--;
row--;
noref++;
}else if(state==MODE_DEL){
col--;
del++;
}else if(state==MODE_INS){
row--;
boolean edge=(col<=1 || col>=columns);
ins+=(edge ? 0 : 1);
clip+=(edge ? 1 : 0);
}else{
assert(false) : state;
}
}
assert(row==0 || col==0);
if(col!=row){//Not sure what this is doing
while(row>0){
clip++;
row--;
col--;
}
if(col>0){
//do nothing
}
}
if(extra!=null){
assert(extra.length==5);
extra[0]=match;
extra[1]=sub;
extra[2]=del;
extra[3]=ins;
extra[4]=noref;
extra[5]=clip;
}
float len=match+sub+ins+del+noref*0.1f;
float id=match/Tools.max(1.0f, len);
return id;
}
/** @return {score, bestRefStart, bestRefStop} */
@Override
public final int[] score(final byte[] read, final byte[] ref, final int refStartLoc, final int refEndLoc,
final int maxRow, final int maxCol, final int maxState/*, final int maxScore, final int maxStart*/){
int row=maxRow;
int col=maxCol;
int state=maxState;
assert(maxState>=0 && maxState<packed.length) :
maxState+", "+maxRow+", "+maxCol+"\n"+new String(read)+"\n"+toString(ref, refStartLoc, refEndLoc);
assert(maxRow>=0 && maxRow<packed.length) :
maxState+", "+maxRow+", "+maxCol+"\n"+new String(read)+"\n"+toString(ref, refStartLoc, refEndLoc);
assert(maxCol>=0 && maxCol<packed[0].length) :
maxState+", "+maxRow+", "+maxCol+"\n"+new String(read)+"\n"+toString(ref, refStartLoc, refEndLoc);
int score=packed[maxRow][maxCol]&SCOREMASK; //Or zero, if it is to be recalculated
if(row<rows){
int difR=rows-row;
int difC=columns-col;
while(difR>difC){
score+=POINTSoff_NOREF;
difR--;
}
row+=difR;
col+=difR;
}
assert(refStartLoc<=refEndLoc);
assert(row==rows);
final int bestRefStop=refStartLoc+col-1;
while(row>0 && col>0){
// final byte c=read[row-1];
// final byte r=ref[refStartLoc+col-1];
// final boolean defined=(AminoAcid.isFullyDefined(c) && AminoAcid.isFullyDefined(r));
state=(packed[row][col]&MODEMASK);
if(state==MODE_MATCH){
col--;
row--;
}else if(state==MODE_SUB){
col--;
row--;
}else if(state==MODE_N){
col--;
row--;
}else if(state==MODE_DEL){
col--;
}else if(state==MODE_INS){
row--;
}else{
assert(false) : state;
}
}
// assert(false) : row+", "+col;
if(row>col){
col-=row;
}
final int bestRefStart=refStartLoc+col;
score>>=SCOREOFFSET;
// System.err.println("t2\t"+score+", "+maxScore+", "+maxStart+", "+bestRefStart);
int[] rvec;
if(bestRefStart<refStartLoc || bestRefStop>refEndLoc){ //Suggest extra padding in cases of overflow
int padLeft=Tools.max(0, refStartLoc-bestRefStart);
int padRight=Tools.max(0, bestRefStop-refEndLoc);
rvec=new int[] {score, bestRefStart, bestRefStop, padLeft, padRight};
}else{
rvec=new int[] {score, bestRefStart, bestRefStop};
}
return rvec;
}
/** Will not fill areas that cannot match minScore.
* @return {score, bestRefStart, bestRefStop} */
@Override
public final int[] fillAndScoreLimited(byte[] read, byte[] ref, int refStartLoc, int refEndLoc, int minScore){
int a=Tools.max(0, refStartLoc);
int b=Tools.min(ref.length-1, refEndLoc);
assert(b>=a);
if(b-a>=maxColumns){
System.err.println("Warning: Max alignment columns exceeded; restricting range. "+(b-a+1)+" > "+maxColumns);
assert(false) : refStartLoc+", "+refEndLoc;
b=Tools.min(ref.length-1, a+maxColumns-1);
}
int[] max=fillLimited(read, ref, a, b, minScore);
// return max==null ? null : new int[] {max[3], 0, max[1]};
int[] score=(max==null ? null : score(read, ref, a, b, max[0], max[1], max[2]/*, max[3], max[4]*/));
return score;
}
public static final String toString(byte[] ref, int startLoc, int stopLoc){
StringBuilder sb=new StringBuilder(stopLoc-startLoc+1);
for(int i=startLoc; i<=stopLoc; i++){sb.append((char)ref[i]);}
return sb.toString();
}
// public int maxScoreByIdentity(int len, float identity){
// assert(identity>=0 && identity<=1);
// return (int)(len*(identity*POINTS_MATCH+(1-identity)*POINTS_SUB));
// }
@Override
public int minScoreByIdentity(int len, float identity){
assert(identity>=0 && identity<=1);
int a=(int)(len*(identity*POINTS_MATCH+(1-identity)*POINTS_SUB));
int b=(int)(len*(identity*POINTS_MATCH+(1-identity)*POINTS_INS));
int c=(int)(len*(1*POINTS_MATCH+((1/(Tools.max(identity, 0.000001f)))-1)*POINTS_DEL));
return Tools.min(a, b, c);
}
private static int calcDelScoreOffset(int len){
if(len<=0){return 0;}
int score=POINTSoff_DEL*len;
return score;
}
//
// public static int calcInsScore(int len){
// if(len<=0){return 0;}
// int score=POINTS_INS;
//
// if(len>1){
// score+=(len-1)*POINTS_INS2;
// }
// return score;
// }
//
// private static int calcInsScoreOffset(int len){
// if(len<=0){return 0;}
// int score=POINTSoff_INS;
//
// if(len>1){
// score+=(len-1)*POINTSoff_INS2;
// }
// return score;
// }
@Override
public int rows(){return rows;}
@Override
public int columns(){return columns;}
private int maxRows;
private int maxColumns;
private int[][] packed;
public static final int MODEBITS=3;
public static final int STARTBITS=9;
public static final int LOWBITS=MODEBITS+STARTBITS;
public static final int SCOREBITS=32-STARTBITS;
public static final int MAX_START=((1<<STARTBITS)-1);
public static final int MAX_SCORE=((1<<(SCOREBITS-1))-1)-2000;
public static final int MIN_SCORE=0-MAX_SCORE; //Keeps it 1 point above "BAD".
public static final int STARTOFFSET=MODEBITS;
public static final int SCOREOFFSET=LOWBITS;
public static final int MODEMASK=~((-1)<<MODEBITS);
public static final int STARTMASK=(~((-1)<<STARTBITS))<<STARTOFFSET;
public static final int SCOREMASK=(~((-1)<<SCOREBITS))<<SCOREOFFSET;
public static final int HIGHMASK=SCOREMASK|STARTMASK;
//For some reason changing MODE_DEL from 1 to 0 breaks everything
private static final byte MODE_DEL=1;
private static final byte MODE_INS=2;
private static final byte MODE_SUB=3;
private static final byte MODE_MATCH=4;
private static final byte MODE_N=5;
public static final int POINTS_NOREF=-15;
public static final int POINTS_MATCH=100;
public static final int POINTS_SUB=-50;
public static final int POINTS_INS=-121;
public static final int POINTS_DEL=-111;
public static final int BAD=MIN_SCORE-1;
public static final int POINTSoff_NOREF=(POINTS_NOREF<<SCOREOFFSET);
public static final int POINTSoff_NOREF_MODE_SUB=POINTSoff_NOREF|MODE_SUB;
public static final int POINTSoff_MATCH=(POINTS_MATCH<<SCOREOFFSET);
public static final int POINTSoff_SUB=(POINTS_SUB<<SCOREOFFSET);
public static final int POINTSoff_INS=(POINTS_INS<<SCOREOFFSET);
public static final int POINTSoff_DEL=(POINTS_DEL<<SCOREOFFSET);
public static final int BADoff=(BAD<<SCOREOFFSET);
private int rows;
private int columns;
// public long iterationsLimited=0;
// public long iterationsUnlimited=0;
public boolean verbose=false;
public boolean verbose2=false;
}
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