Compares each read to the HLA dictionary and outputs closest allele, as well as other stats
git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@1693 348d0f76-0448-11de-a6fe-93d51630548a
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sjia
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/*
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* FindClosestAlleleWalker finds the most similar HLA allele per read
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*/
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package org.broadinstitute.sting.playground.gatk.walkers.HLAcaller;
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import net.sf.samtools.SAMRecord;
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import org.broadinstitute.sting.gatk.contexts.AlignmentContext;
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import org.broadinstitute.sting.gatk.walkers.*;
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import java.io.FileInputStream;
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import java.io.BufferedReader;
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import java.io.DataInputStream;
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import java.io.InputStreamReader;
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import java.util.ArrayList;
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import java.util.Hashtable;
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import java.util.List;
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import java.lang.Math;
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/**
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*
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* @author shermanjia
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*/
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@Requires({DataSource.READS, DataSource.REFERENCE})
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public class FindClosestAlleleWalker extends ReadWalker<Integer, Integer> {
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String HLAdatabaseFile ="/humgen/gsa-scr1/GSA/sjia/454_HLA/HLA/HLA.4digitUnique.sam";
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String CaucasianAlleleFrequencyFile = "/humgen/gsa-scr1/GSA/sjia/454_HLA/HLA/HLA_CaucasiansUSA.freq";
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boolean DatabaseLoaded = false;
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boolean DEBUG = true;
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ArrayList<String> HLAreads = new ArrayList<String>();
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ArrayList<String> HLAcigars = new ArrayList<String>();
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ArrayList<String> HLAnames = new ArrayList<String>();
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ArrayList<String> HLApositions = new ArrayList<String>();
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double[] SingleAlleleFrequencies;
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int numHLAlleles = 0;
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int[] HLAstartpos;
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int[] HLAstoppos;
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Hashtable AlleleFrequencies = new Hashtable();
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int iAstart = -1, iAstop = -1, iBstart = -1, iBstop = -1, iCstart = -1, iCstop = -1;
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public Integer reduceInit() {
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if (!DatabaseLoaded){
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try{
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out.printf("Reading HLA database ...");
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FileInputStream fstream = new FileInputStream(HLAdatabaseFile);
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DataInputStream in = new DataInputStream(fstream);
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BufferedReader br = new BufferedReader(new InputStreamReader(in));
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String strLine; String [] s = null;
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//Read File Line By Line
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int i = 0;
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while ((strLine = br.readLine()) != null) {
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s = strLine.split("\\t");
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if (s.length>=10){
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//Parse the reads with cigar parser
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HLAreads.add(CigarFormatted(s[5],s[9]));
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HLAcigars.add(s[5]);
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HLAnames.add(s[0]);
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HLApositions.add(s[3]);
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if (s[0].indexOf("HLA_A") > -1){
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if (iAstart < 0){iAstart=i;}
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iAstop = i; i++;
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}else if (s[0].indexOf("HLA_B") > -1){
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if (iBstart < 0){iBstart=i;}
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iBstop = i; i++;
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}else if (s[0].indexOf("HLA_C") > -1){
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if (iCstart < 0){iCstart=i;}
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iCstop = i; i++;
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}
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}
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}
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in.close();
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int n = HLApositions.size(); numHLAlleles = n;
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HLAstartpos = new int[n]; HLAstoppos = new int[n];
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SingleAlleleFrequencies = new double[n];
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for (i = 0; i < n; i++){
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//Find start and stop positions for each allele
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HLAstartpos[i]=Integer.parseInt(HLApositions.get(i));
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HLAstoppos[i]=HLAstartpos[i]+HLAreads.get(i).length()-1;
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SingleAlleleFrequencies[i]=0.0;
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//Initialize matrix of probabilities / likelihoods
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}
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out.printf("DONE! Read %s alleles\n",HLAreads.size());
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}catch (Exception e){//Catch exception if any
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System.err.println("Error: " + e.getMessage());
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}
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try{
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out.printf("Reading allele frequences ...");
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FileInputStream fstream = new FileInputStream(CaucasianAlleleFrequencyFile);
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DataInputStream in = new DataInputStream(fstream);
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BufferedReader br = new BufferedReader(new InputStreamReader(in));
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String strLine; String [] s = null;
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//Read File Line By Line
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int count = 0;
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while ((strLine = br.readLine()) != null) {
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s = strLine.split("\\t");
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AlleleFrequencies.put(s[0], s[1]);
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count++;
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}
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in.close();
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out.printf("Done! Read %s alleles\n",count);
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}catch (Exception e){//Catch exception if any
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System.err.println("Error: " + e.getMessage());
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}
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DatabaseLoaded = true;
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out.printf("Comparing reads to database ...\n");
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if (DEBUG){
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//out.printf("Astart[%s]\tAstop[%s]\tBstart[%s]\tBstop[%s]\tCstart[%s]\tCstop[%s]\tnumAlleles[%s]\n",iAstart,iAstop,iBstart,iBstop,iCstart,iCstop,numHLAlleles);
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}
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}
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return 0;
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}
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private String CigarFormatted(String cigar, String read){
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// returns a cigar-formatted sequence (removes insertions, inserts 'D' to where deletions occur
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String formattedRead = ""; char c; String count;
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int cigarPlaceholder = 0; int subcigarLength = 0;
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int readPlaceholder = 0; int subreadLength = 0;
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//reads cigar string
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for (int i = 0; i < cigar.length(); i++){
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c = cigar.charAt(i);
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if (c == 'M'){
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//If reach M for match/mismatch, get number immediately preceeding 'M' and tack on that many characters to sequence
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subcigarLength = i-cigarPlaceholder;
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count = cigar.substring(cigarPlaceholder, i);
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subreadLength = Integer.parseInt(count);
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formattedRead = formattedRead + read.substring(readPlaceholder, readPlaceholder+subreadLength);
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//increment placeholders
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cigarPlaceholder = i+1;
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readPlaceholder = readPlaceholder + subreadLength;
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} else if (c == 'I'){
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//***NOTE: To be modified later if needed (insertions removed here)***
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//If reaches I for insertion, get number before 'I' and skip that many characters in sequence
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count = cigar.substring(cigarPlaceholder, i);
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subreadLength = Integer.parseInt(count);
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//increment placeholders without adding inserted bases to sequence (effectively removes insertion).
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cigarPlaceholder = i+1;
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readPlaceholder = readPlaceholder + subreadLength;
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} else if (c == 'H' || c == 'S'){
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//(H = Headers or S = Soft clipped removed here)***
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//If reaches H for insertion, get number before 'H' and skip that many characters in sequence
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count = cigar.substring(cigarPlaceholder, i);
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subreadLength = Integer.parseInt(count);
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//increment cigar placeholder without adding inserted bases to sequence (effectively removes insertion).
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cigarPlaceholder = i+1;
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} else if (c == 'D'){
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//If reaches D for deletion, insert 'D' into sequence as placeholder
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count = cigar.substring(cigarPlaceholder, i);
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subreadLength = Integer.parseInt(count);
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//Add one 'D' for each deleted base
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String deletion = "";
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for (int j = 1; j <= subreadLength; j++){
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deletion = deletion + "D";
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}
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//update placeholders
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formattedRead = formattedRead + deletion;
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cigarPlaceholder = i+1;
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}
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}
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return formattedRead;
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}
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public Integer map(char[] ref, SAMRecord read) {
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int readstart = read.getAlignmentStart();
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int readstop = read.getAlignmentEnd();
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double[] nummatched = new double[HLAreads.size()];
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double[] concordance = new double[HLAreads.size()];
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double[] numcompared = new double[HLAreads.size()];
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double maxConcordance = 0;
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String s1 = CigarFormatted(read.getCigarString(), read.getReadString());
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char c1, c2;
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String s2 = "", name = "";
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//For every allele that overlaps with current read
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for (int i = 0; i < HLAreads.size(); i++){
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nummatched[i] = 0;
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//Get concordance between read and specific allele
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if (DEBUG){
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//out.printf("%s\t%s\t%s\t%s\t%s\t%s\n",read.getReadName(), HLAnames.get(i),readstart,readstop,HLAstartpos[i],HLAstoppos[i]);
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}
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if (readstart <= HLAstoppos[i] && readstop >= HLAstartpos[i]){
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s2 = HLAreads.get(i);
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for (int j = read.getAlignmentStart(); j <= read.getAlignmentEnd(); j++){
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c1 = s1.charAt(j-readstart);
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c2 = s2.charAt(j-HLAstartpos[i]);
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if (DEBUG){
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//out.printf("%s\t%s\t%s\t%s\t%s\t%s\t%s\n",read.getReadName(),HLAnames.get(i),j,j-readstart,j-HLAstartpos[i],c1,c2);
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}
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if (c1 != 'D'){
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numcompared[i]++;
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if (c1 == c2){
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nummatched[i]++;
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}
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}
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}
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}
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concordance[i]=nummatched[i]/numcompared[i];
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if (concordance[i] > maxConcordance){maxConcordance = concordance[i];}
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}
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double freq, maxFreq = 0.0;
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for (int i = 0; i < HLAreads.size(); i++){
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if (concordance[i] == maxConcordance && maxConcordance > 0){
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name=HLAnames.get(i).substring(4);
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if (AlleleFrequencies.containsKey(name)){
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freq = Double.parseDouble((String) AlleleFrequencies.get(name).toString());
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}else{
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freq=0.0001;
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}
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if (freq > maxFreq){maxFreq = freq;}
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}
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}
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out.printf("%s", read.getReadName());
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for (int i = 0; i < HLAreads.size(); i++){
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if (concordance[i] == maxConcordance && maxConcordance > 0){
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name=HLAnames.get(i).substring(4);
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if (AlleleFrequencies.containsKey(name)){
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freq = Double.parseDouble((String) AlleleFrequencies.get(name).toString());
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}else{
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freq=0.0001;
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}
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if (freq == maxFreq){
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out.printf("\t%s\t%.3f\t%.0f\t%.0f\t%.3f",HLAnames.get(i),concordance[i],numcompared[i],numcompared[i]-nummatched[i],freq);
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}
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}
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}
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out.print("\n");
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return 1;
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}
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public Integer reduce(Integer value, Integer sum) {
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return value + sum;
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}
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}
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