/* * Copyright (c) 2010, The Broad Institute * * Permission is hereby granted, free of charge, to any person * obtaining a copy of this software and associated documentation * files (the "Software"), to deal in the Software without * restriction, including without limitation the rights to use, * copy, modify, merge, publish, distribute, sublicense, and/or sell * copies of the Software, and to permit persons to whom the * Software is furnished to do so, subject to the following * conditions: * * The above copyright notice and this permission notice shall be * included in all copies or substantial portions of the Software. * THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, * EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES * OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND * NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT * HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, * WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING * FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR * OTHER DEALINGS IN THE SOFTWARE. */ package org.broadinstitute.sting.utils; import net.sf.samtools.CigarElement; import net.sf.samtools.CigarOperator; import net.sf.samtools.Cigar; import java.util.List; import java.util.ArrayList; import java.util.Collections; import java.util.Arrays; /** * Created by IntelliJ IDEA. * User: asivache * Date: Mar 23, 2009 * Time: 1:54:54 PM * To change this template use File | Settings | File Templates. */ public class SWPairwiseAlignment { private int alignment_offset; // offset of s2 w/respect to s1 private Cigar alignmentCigar; private final double w_match; private final double w_mismatch; private final double w_open; private final double w_extend; private static final int MSTATE = 0; private static final int ISTATE = 1; private static final int DSTATE = 2; // private double [] best_gap_v ; // private int [] gap_size_v ; // private double [] best_gap_h ; // private int [] gap_size_h ; // private static double [][] sw = new double[500][500]; // private static int [][] btrack = new int[500][500]; // ************************************************************************ // **** IMPORTANT NOTE: **** // **** This class assumes that all bytes come from UPPERCASED chars! **** // ************************************************************************ public SWPairwiseAlignment(byte[] seq1, byte[] seq2, double match, double mismatch, double open, double extend ) { w_match = match; w_mismatch = mismatch; w_open = open; w_extend = extend; align(seq1,seq2); } public SWPairwiseAlignment(byte[] seq1, byte[] seq2) { this(seq1,seq2,1.0,-1.0/3.0,-1.0-1.0/3.0,-1.0/3.0); // match=1, mismatch = -1/3, gap=-(1+k/3) } public Cigar getCigar() { return alignmentCigar ; } public int getAlignmentStart2wrt1() { return alignment_offset; } public void align(final byte[] a, final byte[] b) { final int n = a.length; final int m = b.length; double [] sw = new double[(n+1)*(m+1)]; int [] btrack = new int[(n+1)*(m+1)]; // best_gap_v = new double[m+1]; // Arrays.fill(best_gap_v,-1.0e40); // gap_size_v = new int[m+1]; // best_gap_h = new double[n+1]; // Arrays.fill(best_gap_h,-1.0e40); // gap_size_h = new int[n+1]; calculateMatrix(a, b, sw, btrack); calculateCigar(n, m, sw, btrack); // length of the segment (continuous matches, insertions or deletions) } private void calculateMatrix(final byte[] a, final byte[] b, double [] sw, int [] btrack ) { final int n = a.length+1; final int m = b.length+1; double [] best_gap_v = new double[m+1]; Arrays.fill(best_gap_v,-1.0e40); int [] gap_size_v = new int[m+1]; double [] best_gap_h = new double[n+1]; Arrays.fill(best_gap_h,-1.0e40); int [] gap_size_h = new int[n+1]; // build smith-waterman matrix and keep backtrack info: for ( int i = 1, row_offset_1 = 0 ; i < n ; i++ ) { // we do NOT update row_offset_1 here, see comment at the end of this outer loop byte a_base = a[i-1]; // letter in a at the current pos final int row_offset = row_offset_1 + m; // On the entrance into the loop, row_offset_1 is the (linear) offset // of the first element of row (i-1) and row_offset is the linear offset of the // start of row i for ( int j = 1, data_offset_1 = row_offset_1 ; j < m ; j++, data_offset_1++ ) { // data_offset_1 is linearized offset of element [i-1][j-1] final byte b_base = b[j-1]; // letter in b at the current pos // in other words, step_diag = sw[i-1][j-1] + wd(a_base,b_base); double step_diag = sw[data_offset_1] + wd(a_base,b_base); // optimized "traversal" of all the matrix cells above the current one (i.e. traversing // all 'step down' events that would end in the current cell. The optimized code // does exactly the same thing as the commented out loop below. IMPORTANT: // the optimization works ONLY for linear w(k)=wopen+(k-1)*wextend!!!! // if a gap (length 1) was just opened above, this is the cost of arriving to the current cell: double prev_gap = sw[data_offset_1+1]+w_open; best_gap_v[j] += w_extend; // for the gaps that were already opened earlier, extending them by 1 costs w_extend if ( prev_gap > best_gap_v[j] ) { // opening a gap just before the current cell results in better score than extending by one // the best previously opened gap. This will hold for ALL cells below: since any gap // once opened always costs w_extend to extend by another base, we will always get a better score // by arriving to any cell below from the gap we just opened (prev_gap) rather than from the previous best gap best_gap_v[j] = prev_gap; gap_size_v[j] = 1; // remember that the best step-down gap from above has length 1 (we just opened it) } else { // previous best gap is still the best, even after extension by another base, so we just record that extension: gap_size_v[j]++; } final double step_down = best_gap_v[j] ; final int kd = gap_size_v[j]; /* for ( int k = 1, data_offset_k = data_offset_1+1 ; k < i ; k++, data_offset_k -= m ) { // data_offset_k is linearized offset of element [i-k][j] // in other words, trial = sw[i-k][j]+gap_penalty: final double trial = sw[data_offset_k]+wk(k); if ( step_down < trial ) { step_down=trial; kd = k; } } */ // optimized "traversal" of all the matrix cells to the left of the current one (i.e. traversing // all 'step right' events that would end in the current cell. The optimized code // does exactly the same thing as the commented out loop below. IMPORTANT: // the optimization works ONLY for linear w(k)=wopen+(k-1)*wextend!!!! final int data_offset = row_offset + j; // linearized offset of element [i][j] prev_gap = sw[data_offset-1]+w_open; // what would it cost us to open length 1 gap just to the left from current cell best_gap_h[i] += w_extend; // previous best gap would cost us that much if extended by another base if ( prev_gap > best_gap_h[i] ) { // newly opened gap is better (score-wise) than any previous gap with the same row index i; since // gap penalty is linear with k, this new gap location is going to remain better than any previous ones best_gap_h[i] = prev_gap; gap_size_h[i] = 1; } else { gap_size_h[i]++; } final double step_right = best_gap_h[i]; final int ki = gap_size_h[i]; /* for ( int k = 1, data_offset = row_offset+j-1 ; k < j ; k++, data_offset-- ) { // data_offset is linearized offset of element [i][j-k] // in other words, step_right=sw[i][j-k]+gap_penalty; final double trial = sw[data_offset]+wk(k); if ( step_right < trial ) { step_right=trial; ki = k; } } final int data_offset = row_offset + j; // linearized offset of element [i][j] */ if ( step_down > step_right ) { if ( step_down > step_diag ) { sw[data_offset] = Math.max(0,step_down); btrack[data_offset] = kd ; // positive=vertical } else { sw[data_offset] = Math.max(0,step_diag); btrack[data_offset] = 0; // 0 = diagonal } } else { // step_down <= step_right if ( step_right > step_diag ) { sw[data_offset] = Math.max(0,step_right); btrack[data_offset] = -ki; // negative = horizontal } else { sw[data_offset] = Math.max(0,step_diag); btrack[data_offset] = 0; // 0 = diagonal } } // sw[data_offset] = Math.max(0, Math.max(step_diag,Math.max(step_down,step_right))); } // IMPORTANT, IMPORTANT, IMPORTANT: // note that we update this (secondary) outer loop variable here, // so that we DO NOT need to update it // in the for() statement itself. row_offset_1 = row_offset; } // print(sw,a,b); } private void calculateCigar(int n, int m, double [] sw, int [] btrack) { // p holds the position we start backtracking from; we will be assembling a cigar in the backwards order //PrimitivePair.Int p = new PrimitivePair.Int(); int p1 = 0, p2 = 0; double maxscore = 0.0; int segment_length = 0; // length of the segment (continuous matches, insertions or deletions) // look for largest score. we use >= combined with the traversal direction // to ensure that if two scores are equal, the one closer to diagonal gets picked for ( int i = 1, data_offset = m+1+m ; i < n+1 ; i++, data_offset += (m+1) ) { // data_offset is the offset of [i][m] if ( sw[data_offset] >= maxscore ) { p1 = i; p2 = m ; maxscore = sw[data_offset]; } } for ( int j = 1, data_offset = n*(m+1)+1 ; j < m+1 ; j++, data_offset++ ) { // data_offset is the offset of [n][j] if ( sw[data_offset] > maxscore || sw[data_offset] == maxscore && Math.abs(n-j) < Math.abs(p1 - p2)) { p1 = n; p2 = j ; // maxscore = sw[n][j]; maxscore = sw[data_offset]; segment_length = m - j ; // end of sequence 2 is overhanging; we will just record it as 'M' segment } } // we will be placing all insertions and deletions into sequence b, so the state are named w/regard // to that sequence int state = MSTATE; List lce = new ArrayList(5); int data_offset = p1*(m+1)+p2; // offset of element [p1][p2] do { // int btr = btrack[p1][p2]; int btr = btrack[data_offset]; int step_left = ( btr < 0 ? -btr : 1); int step_up = ( btr > 0 ? btr : 1 ); int new_state; if ( btr > 0 ) new_state = DSTATE; else if ( btr < 0 ) new_state = ISTATE; else new_state = MSTATE; int step_length = 1; // move to next best location in the sw matrix: switch( new_state ) { case MSTATE: data_offset -= (m+2); break; // equivalent to p1--; p2-- case ISTATE: data_offset -= step_left; step_length = step_left; break; // equivalent to p2-=step_left; case DSTATE: data_offset -= (m+1)*step_up; step_length = step_up; break; // equivalent to p1 -= step_up } // now let's see if the state actually changed: if ( new_state == state ) segment_length+=step_length; else { // state changed, lets emit previous segment, whatever it was (Insertion Deletion, or (Mis)Match). lce.add(makeElement(state, segment_length)); segment_length = step_length; state = new_state; } // next condition is equivalent to while ( sw[p1][p2] != 0 ) (with modified p1 and/or p2: } while ( sw[data_offset] != 0 ); // reinstate last values of p1, p2 we arrived to after matrix traversal: p1 = data_offset / (m+1); p2 = data_offset % (m+1); // post-process the last segment we are still keeping lce.add(makeElement(state, segment_length + p2)); alignment_offset = p1 - p2; Collections.reverse(lce); alignmentCigar = new Cigar(lce); } private CigarElement makeElement(int state, int segment_length) { CigarOperator o = null; switch(state) { case MSTATE: o = CigarOperator.M; break; case ISTATE: o = CigarOperator.I; break; case DSTATE: o = CigarOperator.D; break; } return new CigarElement(segment_length,o); } private double wd(byte x, byte y) { return (x == y ? w_match : w_mismatch); } private double wk(int k) { return w_open+(k-1)*w_extend; // gap } private void print(int[][] s) { for ( int i = 0 ; i < s.length ; i++) { for ( int j = 0; j < s[i].length ; j++ ) { System.out.printf(" %4d",s[i][j]); } System.out.println(); } } private void print(double[][] s) { for ( int i = 0 ; i < s.length ; i++) { for ( int j = 0; j < s[i].length ; j++ ) { System.out.printf(" %4g",s[i][j]); } System.out.println(); } } private void print(int[][] s, String a, String b) { System.out.print(" "); for ( int j = 1 ; j < s[0].length ; j++) System.out.printf(" %4c",b.charAt(j-1)) ; System.out.println(); for ( int i = 0 ; i < s.length ; i++) { if ( i > 0 ) System.out.print(a.charAt(i-1)); else System.out.print(' '); System.out.print(" "); for ( int j = 0; j < s[i].length ; j++ ) { System.out.printf(" %4d",s[i][j]); } System.out.println(); } } private void print(double[][] s, String a, String b) { System.out.print(""); for ( int j = 1 ; j < s[0].length ; j++) System.out.printf(" %4c",b.charAt(j-1)) ; System.out.println(); for ( int i = 0 ; i < s.length ; i++) { if ( i > 0 ) System.out.print(a.charAt(i-1)); else System.out.print(' '); System.out.print(" "); for ( int j = 0; j < s[i].length ; j++ ) { System.out.printf(" %2.1f",s[i][j]); } System.out.println(); } } /* ############################################## BELOW: main() method for testing; old implementations of the core methods are commented out below; uncomment everything through the end of the file if benchmarking of new vs old implementations is needed. public static void main(String argv[]) { String ref="CACGAGCATATGTGTACATGAATTTGTATTGCACATGTGTTTAATGCGAACACGTGTCATGTGTATGTGTTCACATGCATGTGTGTCT"; String read = "GCATATGTTTACATGAATTTGTATTGCACATGTGTTTAATGCGAACACGTGTCATGTGTGTGTTCACATGCATGTG"; long start = System.currentTimeMillis(); SWPairwiseAlignment a = null; for ( int i = 0 ; i < 10000 ; i++ ) { a = new SWPairwiseAlignment(ref.getBytes(),read.getBytes(),true); } long stop1 = System.currentTimeMillis(); for ( int i = 0 ; i < 10000 ; i++ ) { a = new SWPairwiseAlignment(ref.getBytes(),read.getBytes(),false); } long stop2 = System.currentTimeMillis(); System.out.println("start="+a.getAlignmentStart2wrt1()+", cigar="+a.getCigar()+" length1="+ref.length()+" length2="+read.length()); long timeold = stop1-start; long timenew = stop2-stop1; System.out.println("TOTAL TIME OLD: "+(float)(timeold)/1000); System.out.println("TOTAL TIME NEW: "+(float)(timenew)/1000); System.out.println("Fold change: " + ((float) timeold)/timenew); } public SWPairwiseAlignment(byte[] seq1, byte[] seq2, double match, double mismatch, double open, double extend, boolean runOld ) { w_match = match; w_mismatch = mismatch; w_open = open; w_extend = extend; if ( runOld ) align_old(seq1,seq2); else align(seq1,seq2); } public SWPairwiseAlignment(byte[] seq1, byte[] seq2, boolean runOld) { this(seq1,seq2,1.0,-1.0/3.0,-1.0-1.0/3.0,-1.0/3.0,runOld); // match=1, mismatch = -1/3, gap=-(1+k/3) } public void align_old(final byte[] a, final byte[] b) { final int n = a.length; final int m = b.length; double [] sw = new double[(n+1)*(m+1)]; int [] btrack = new int[(n+1)*(m+1)]; calculateMatrix_old(a, b, sw, btrack); calculateCigar(n, m, sw, btrack); // length of the segment (continuous matches, insertions or deletions) } private void calculateMatrix_old(final byte[] a, final byte[] b, double [] sw, int [] btrack ) { final int n = a.length+1; final int m = b.length+1; // build smith-waterman matrix and keep backtrack info: for ( int i = 1, row_offset_1 = 0 ; i < n ; i++ ) { // we do NOT update row_offset_1 here, see comment at the end of this outer loop byte a_base = a[i-1]; // letter in a at the current pos final int row_offset = row_offset_1 + m; // On the entrance into the loop, row_offset_1 is the (linear) offset // of the first element of row (i-1) and row_offset is the linear offset of the // start of row i for ( int j = 1, data_offset_1 = row_offset_1 ; j < m ; j++, data_offset_1++ ) { // data_offset_1 is linearized offset of element [i-1][j-1] final byte b_base = b[j-1]; // letter in b at the current pos // in other words, step_diag = sw[i-1][j-1] + wd(a_base,b_base); double step_diag = sw[data_offset_1] + wd(a_base,b_base); int kd = 0; double step_down = 0; for ( int k = 1, data_offset_k = data_offset_1+1 ; k < i ; k++, data_offset_k -= m ) { // data_offset_k is linearized offset of element [i-k][j] // in other words, trial = sw[i-k][j]+gap_penalty: final double trial = sw[data_offset_k]+wk(k); if ( step_down < trial ) { step_down=trial; kd = k; } } int ki = 0; // optimized "traversal" of all the matrix cells to the left of the current one (i.e. traversing // all 'step right' events that would end in the current cell. The optimized code // does exactly the same thing as the commented out loop below. IMPORTANT: // the optimization works ONLY for linear w(k)=wopen+(k-1)*wextend!!!! double step_right = 0; for ( int k = 1, data_offset = row_offset+j-1 ; k < j ; k++, data_offset-- ) { // data_offset is linearized offset of element [i][j-k] // in other words, step_right=sw[i][j-k]+gap_penalty; final double trial = sw[data_offset]+wk(k); if ( step_right < trial ) { step_right=trial; ki = k; } } final int data_offset = row_offset + j; // linearized offset of element [i][j] if ( step_down > step_right ) { if ( step_down > step_diag ) { sw[data_offset] = Math.max(0,step_down); btrack[data_offset] = kd ; // positive=vertical } else { sw[data_offset] = Math.max(0,step_diag); btrack[data_offset] = 0; // 0 = diagonal } } else { // step_down <= step_right if ( step_right > step_diag ) { sw[data_offset] = Math.max(0,step_right); btrack[data_offset] = -ki; // negative = horizontal } else { sw[data_offset] = Math.max(0,step_diag); btrack[data_offset] = 0; // 0 = diagonal } } // sw[data_offset] = Math.max(0, Math.max(step_diag,Math.max(step_down,step_right))); } // IMPORTANT, IMPORTANT, IMPORTANT: // note that we update this (secondary) outer loop variable here, // so that we DO NOT need to update it // in the for() statement itself. row_offset_1 = row_offset; } // print(sw,a,b); } ##################### END COMMENTED OUT SECTION */ }