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Behold MultiSampleCaller! 

Complete re-write of PoolCaller algorithm, now basically beta quality code. 

Improvements over PoolCaller include:

	- more correct strand test
	- fractional counts from genotypes (which means no individual lod threshold needed)
	- signifigantly cleaner code; first beta-quality code I've written since BaitDesigner so long ago.
	- faster, less likely to crash!	




git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@1020 348d0f76-0448-11de-a6fe-93d51630548a
This commit is contained in:
jmaguire 2009-06-16 20:03:24 +00:00
parent 7db4497013
commit 4f6d26849f
7 changed files with 892 additions and 123 deletions
Show Stats Download Patch File Download Diff File Expand all files Collapse all files

120
java/src/org/broadinstitute/sting/playground/gatk/walkers/CoverageBySample.java
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@ -9,6 +9,8 @@ import org.broadinstitute.sting.gatk.LocusContext;
import org.broadinstitute.sting.playground.gatk.walkers.AlleleFrequencyWalker; import org.broadinstitute.sting.playground.gatk.walkers.AlleleFrequencyWalker;
import org.broadinstitute.sting.playground.utils.AlleleFrequencyEstimate; import org.broadinstitute.sting.playground.utils.AlleleFrequencyEstimate;
import org.broadinstitute.sting.utils.cmdLine.Argument; import org.broadinstitute.sting.utils.cmdLine.Argument;
import org.broadinstitute.sting.utils.Utils;
import org.broadinstitute.sting.utils.BaseUtils;
import java.util.*; import java.util.*;
@ -41,14 +43,48 @@ public class CoverageBySample extends LocusWalker<String, String>
public String map(RefMetaDataTracker tracker, char ref, LocusContext context) public String map(RefMetaDataTracker tracker, char ref, LocusContext context)
{ {
String line = context.getLocation().getContig() + " " + context.getLocation().getStart() + " " ; String line = context.getLocation().getContig() + " " + context.getLocation().getStart() + " " ;
LocusContext[] contexts = filterLocusContext(context, sample_names, 0);
HashMap<String,Integer> counts = countReadsBySample(context); HashMap<String,Integer> counts = countReadsBySample(context);
for (int i = 0; i < sample_names.size(); i++) for (int i = 0; i < contexts.length; i++)
{ {
int count = counts.get(sample_names.get(i)); List<SAMRecord> reads = contexts[i].getReads();
line += " " + count; List<Integer> offsets = contexts[i].getOffsets();
out.printf("%s %s ", context.getLocation(), sample_names.get(i));
int[] forward_counts = new int[4];
int[] backward_counts = new int[4];
for (int j = 0; j < reads.size(); j++)
{
SAMRecord read = reads.get(j);
int offset = offsets.get(j);
boolean backward = read.getReadNegativeStrandFlag();
char base = Character.toUpperCase((char)(read.getReadBases()[offset]));
if (BaseUtils.simpleBaseToBaseIndex(base) == -1) { continue; }
if (backward) { base = Character.toLowerCase(base); }
if (! backward) { forward_counts[BaseUtils.simpleBaseToBaseIndex(base)]++; }
else { backward_counts[BaseUtils.simpleBaseToBaseIndex(base)]++; }
//out.printf("%c", base);
}
out.printf("A[%d] C[%d] G[%d] T[%d] a[%d] c[%d] g[%d] t[%d]",
forward_counts[0],
forward_counts[1],
forward_counts[2],
forward_counts[3],
backward_counts[0],
backward_counts[1],
backward_counts[2],
backward_counts[3]);
out.printf("\n");
} }
line += "\n"; return "";
return line;
} }
private HashMap<String,Integer> countReadsBySample(LocusContext context) private HashMap<String,Integer> countReadsBySample(LocusContext context)
@ -68,13 +104,80 @@ public class CoverageBySample extends LocusWalker<String, String>
return counts; return counts;
} }
public void onTraversalDone() private LocusContext[] filterLocusContext(LocusContext context, List<String> sample_names, int downsample)
{
HashMap<String,Integer> index = new HashMap<String,Integer>();
for (int i = 0; i < sample_names.size(); i++)
{
index.put(sample_names.get(i), i);
}
LocusContext[] contexts = new LocusContext[sample_names.size()];
ArrayList<SAMRecord>[] reads = new ArrayList[sample_names.size()];
ArrayList<Integer>[] offsets = new ArrayList[sample_names.size()];
for (int i = 0; i < sample_names.size(); i++)
{
reads[i] = new ArrayList<SAMRecord>();
offsets[i] = new ArrayList<Integer>();
}
for (int i = 0; i < context.getReads().size(); i++)
{
SAMRecord read = context.getReads().get(i);
Integer offset = context.getOffsets().get(i);
String RG = (String)(read.getAttribute("RG"));
assert(header != null);
assert(header.getReadGroup(RG) != null);
String sample = header.getReadGroup(RG).getSample();
//if (SAMPLE_NAME_REGEX != null) { sample = sample.replaceAll(SAMPLE_NAME_REGEX, "$1"); }
reads[index.get(sample)].add(read);
offsets[index.get(sample)].add(offset);
}
if (downsample != 0)
{
for (int j = 0; j < reads.length; j++)
{
List<Integer> perm = new ArrayList<Integer>();
for (int i = 0; i < reads[j].size(); i++) { perm.add(i); }
perm = Utils.RandomSubset(perm, downsample);
ArrayList<SAMRecord> downsampled_reads = new ArrayList<SAMRecord>();
ArrayList<Integer> downsampled_offsets = new ArrayList<Integer>();
for (int i = 0; i < perm.size(); i++)
{
downsampled_reads.add(reads[j].get(perm.get(i)));
downsampled_offsets.add(offsets[j].get(perm.get(i)));
}
reads[j] = downsampled_reads;
offsets[j] = downsampled_offsets;
contexts[j] = new LocusContext(context.getLocation(), reads[j], offsets[j]);
}
}
else
{
for (int j = 0; j < reads.length; j++)
{
contexts[j] = new LocusContext(context.getLocation(), reads[j], offsets[j]);
}
}
return contexts;
}
public void onTraversalDone(String result)
{ {
return; return;
} }
public String reduceInit() public String reduceInit()
{ {
/*
String header = "contig offset"; String header = "contig offset";
for (int i = 0; i < sample_names.size(); i++) for (int i = 0; i < sample_names.size(); i++)
{ {
@ -83,11 +186,14 @@ public class CoverageBySample extends LocusWalker<String, String>
header += "\n"; header += "\n";
out.print(header); out.print(header);
return header; return header;
*/
return "";
} }
public String reduce(String line, String sum) public String reduce(String line, String sum)
{ {
out.print(line); //out.print(line);
out.flush();
return ""; return "";
} }

542
java/src/org/broadinstitute/sting/playground/gatk/walkers/MultiSampleCaller.java 100644
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@ -0,0 +1,542 @@
package org.broadinstitute.sting.playground.gatk.walkers;
import net.sf.samtools.SAMFileHeader;
import net.sf.samtools.SAMReadGroupRecord;
import net.sf.samtools.SAMRecord;
import org.broadinstitute.sting.gatk.GenomeAnalysisEngine;
import org.broadinstitute.sting.gatk.LocusContext;
import org.broadinstitute.sting.gatk.refdata.RefMetaDataTracker;
import org.broadinstitute.sting.gatk.walkers.LocusWalker;
import org.broadinstitute.sting.playground.utils.AlleleFrequencyEstimate;
import org.broadinstitute.sting.playground.utils.*;
import org.broadinstitute.sting.utils.*;
import org.broadinstitute.sting.utils.ReadBackedPileup;
import org.broadinstitute.sting.utils.cmdLine.Argument;
import java.util.*;
import java.util.zip.*;
import java.io.*;
// Beta iterative multi-sample caller
// j.maguire 6-11-2009
public class MultiSampleCaller extends LocusWalker<String,String>
{
@Argument(required=false, shortName="fractional_counts", doc="should we use fractional counts?") public boolean FRACTIONAL_COUNTS = false;
@Argument(required=false, shortName="max_iterations", doc="Maximum number of iterations for EM") public int MAX_ITERATIONS = 10;
@Argument(fullName="lodThreshold", shortName="lod", required=false, doc="lod threshold for outputting individual genotypes") public Double lodThreshold = 0.0;
@Argument(fullName="discovery_output", shortName="discovery_output", required=true, doc="file to write SNP discovery output to") public String DISCOVERY_OUTPUT;
@Argument(fullName="individual_output", shortName="individual_output", required=true, doc="file to write individual SNP calls to") public String INDIVIDUAL_OUTPUT;
@Argument(fullName="sample_name_regex", shortName="sample_name_regex", required=false, doc="sample_name_regex") public String SAMPLE_NAME_REGEX = null;
// Private state.
List<String> sample_names;
private SAMFileHeader header;
PrintStream individual_output_file;
PrintStream discovery_output_file;
/////////
// Walker Interface Functions
public void initialize()
{
try
{
discovery_output_file = new PrintStream(DISCOVERY_OUTPUT);
individual_output_file = new PrintStream(new GZIPOutputStream(new FileOutputStream(INDIVIDUAL_OUTPUT)));
discovery_output_file.println("loc ref alt lod strand_score pD pNull discovery_lod in_dbsnp pA pC pG pT EM_alt_freq EM_N n_ref n_het n_hom pD_fw nNull_fw EM_alt_freq_fw pD_bw pNull_bw EM_alt_freq_bw");
individual_output_file.println("loc ref sample_name genotype lodVsNextBest lodVsRef in_dbsnp AA AC AG AT CC CG CT GG GT TT");
}
catch (Exception e)
{
e.printStackTrace();
System.exit(-1);
}
GenomeAnalysisEngine toolkit = this.getToolkit();
this.header = toolkit.getEngine().getSAMHeader();
List<SAMReadGroupRecord> read_groups = header.getReadGroups();
sample_names = new ArrayList<String>();
HashSet<String> unique_sample_names = new HashSet<String>();
for (int i = 0; i < read_groups.size(); i++)
{
String sample_name = read_groups.get(i).getSample();
if (SAMPLE_NAME_REGEX != null) { sample_name = sample_name.replaceAll(SAMPLE_NAME_REGEX, "$1"); }
if (unique_sample_names.contains(sample_name)) { continue; }
unique_sample_names.add(sample_name);
sample_names.add(sample_name);
System.out.println("SAMPLE: " + sample_name);
}
}
public String in_dbsnp = "novel";
public String map(RefMetaDataTracker tracker, char ref, LocusContext context)
{
this.ref = ref;
if (tracker.lookup("DBSNP", null) != null) { in_dbsnp = "known"; } else { in_dbsnp = "novel"; }
this.MultiSampleCall(context, sample_names);
return null;
}
public void onTraversalDone(String sum)
{
out.println("MultiSampleCaller done.");
return;
}
public String reduceInit()
{
return null;
}
public String reduce(String record, String sum)
{
return null;
}
// END Walker Interface Functions
/////////
/////////
// Calling Functions
char ref;
GenotypeLikelihoods Genotype(LocusContext context, double[] allele_likelihoods)
{
ReadBackedPileup pileup = new ReadBackedPileup(ref, context);
String bases = pileup.getBases();
if (bases.length() == 0)
{
GenotypeLikelihoods G = new GenotypeLikelihoods();
return G;
}
List<SAMRecord> reads = context.getReads();
List<Integer> offsets = context.getOffsets();
ref = Character.toUpperCase(ref);
/*
// Handle indels.
if (call_indels)
{
String[] indels = BasicPileup.indelPileup(reads, offsets);
IndelCall indel_call = GenotypeLikelihoods.callIndel(indels);
if (indel_call != null)
{
if (! indel_call.type.equals("ref"))
{
System.out.printf("INDEL %s %s\n", context.getLocation(), indel_call);
}
}
}
*/
// Handle single-base polymorphisms.
GenotypeLikelihoods G = new GenotypeLikelihoods();
for ( int i = 0; i < reads.size(); i++ )
{
SAMRecord read = reads.get(i);
int offset = offsets.get(i);
G.add(ref, read.getReadString().charAt(offset), read.getBaseQualities()[offset]);
}
G.ApplyPrior(ref, allele_likelihoods);
/*
// Handle 2nd-best base calls.
if (fourBaseMode && pileup.getBases().length() < 750)
{
G.applySecondBaseDistributionPrior(pileup.getBases(), pileup.getSecondaryBasePileup());
}
*/
return G;
}
// thoughly check this function
double[] CountFreqs(GenotypeLikelihoods[] genotype_likelihoods)
{
double[] allele_likelihoods = new double[4];
for (int x = 0; x < genotype_likelihoods.length; x++)
{
if (genotype_likelihoods[x].coverage == 0) { continue; }
double Z = 0;
for(int k = 0; k < 10; k++) { Z += Math.pow(10,genotype_likelihoods[x].likelihoods[k]); }
double[] personal_allele_likelihoods = new double[4];
int k = 0;
for (int i = 0; i < 4; i++)
{
for (int j = i; j < 4; j++)
{
personal_allele_likelihoods[i] += Math.pow(10,genotype_likelihoods[x].likelihoods[k])/Z;
personal_allele_likelihoods[j] += Math.pow(10,genotype_likelihoods[x].likelihoods[k])/Z;
k++;
}
}
double sum = 0;
for (int y = 0; y < 4; y++) { sum += personal_allele_likelihoods[y]; }
for (int y = 0; y < 4; y++) { personal_allele_likelihoods[y] /= sum; }
for (int y = 0; y < 4; y++) { allele_likelihoods[y] += personal_allele_likelihoods[y]; }
}
double sum = 0;
for (int i = 0; i < 4; i++) { sum += allele_likelihoods[i]; }
for (int i = 0; i < 4; i++) { allele_likelihoods[i] /= sum; }
return allele_likelihoods;
}
// Potential precision error here.
double Compute_pD(GenotypeLikelihoods[] genotype_likelihoods)
{
double pD = 0;
for (int i = 0; i < sample_names.size(); i++)
{
double sum = 0;
for (int j = 0; j < 10; j++)
{
sum += Math.pow(10, genotype_likelihoods[i].likelihoods[j]);
}
pD += Math.log10(sum);
}
return pD;
}
double Compute_pNull(LocusContext[] contexts)
{
double[] allele_likelihoods = new double[4];
for (int i = 0; i < 4; i++) { allele_likelihoods[i] = 1e-6/3.0; }
allele_likelihoods[BaseUtils.simpleBaseToBaseIndex(ref)] = 1.0-1e-6;
GenotypeLikelihoods[] G = new GenotypeLikelihoods[sample_names.size()];
for (int j = 0; j < sample_names.size(); j++)
{
G[j] = Genotype(contexts[j], allele_likelihoods);
}
return Compute_pD(G);
}
double LOD(LocusContext[] contexts)
{
EM_Result em_result = EM(contexts);
GenotypeLikelihoods[] G = em_result.genotype_likelihoods;
double pD = Compute_pD(G);
double pNull = Compute_pNull(contexts);
double lod = pD - pNull;
return lod;
}
class EM_Result
{
GenotypeLikelihoods[] genotype_likelihoods;
double[] allele_likelihoods;
int EM_N;
public EM_Result(GenotypeLikelihoods[] genotype_likelihoods, double[] allele_likelihoods)
{
this.genotype_likelihoods = genotype_likelihoods;
this.allele_likelihoods = allele_likelihoods;
EM_N = 0;
for (int i = 0; i < genotype_likelihoods.length; i++)
{
if (genotype_likelihoods[i].coverage > 0) { EM_N += 1; }
}
}
}
EM_Result EM(LocusContext[] contexts)
{
double[] allele_likelihoods = new double[4];
// These initial conditions should roughly replicate classic SSG. (at least on hets)
for (int i = 0; i < 4; i++)
{
if (i == BaseUtils.simpleBaseToBaseIndex(ref)) { allele_likelihoods[i] = 0.9994999; } //sqrt(0.999)
else { allele_likelihoods[i] = 0.0005002502; } // 0.001 / (2 * sqrt(0.999)
}
GenotypeLikelihoods[] G = new GenotypeLikelihoods[sample_names.size()];
for (int i = 0; i < MAX_ITERATIONS; i++)
{
for (int j = 0; j < sample_names.size(); j++)
{
G[j] = Genotype(contexts[j], allele_likelihoods);
}
allele_likelihoods = CountFreqs(G);
}
return new EM_Result(G, allele_likelihoods);
}
// Hacky global variables for debugging.
double pNull_fw;
double pNull_bw;
double pD_fw;
double pD_bw;
double EM_alt_freq_fw;
double EM_alt_freq_bw;
double StrandScore(LocusContext context)
{
LocusContext[] contexts = filterLocusContextBySample(context, sample_names, 0);
LocusContext fw = filterLocusContextByStrand(context, "+");
LocusContext bw = filterLocusContextByStrand(context, "-");
LocusContext[] contexts_fw = filterLocusContextBySample(fw, sample_names, 0);
LocusContext[] contexts_bw = filterLocusContextBySample(bw, sample_names, 0);
EM_Result em_fw = EM(contexts_fw);
EM_Result em_bw = EM(contexts_bw);
pNull_fw = Compute_pNull(contexts_fw);
pNull_bw = Compute_pNull(contexts_bw);
pD_fw = Compute_pD(em_fw.genotype_likelihoods);
pD_bw = Compute_pD(em_bw.genotype_likelihoods);
EM_alt_freq_fw = Compute_alt_freq(ref, em_fw.allele_likelihoods);
EM_alt_freq_bw = Compute_alt_freq(ref, em_bw.allele_likelihoods);
double pNull = Compute_pNull(contexts);
double lod = LOD(contexts);
double lod_fw = (pD_fw + pNull_bw) - pNull;
double lod_bw = (pD_bw + pNull_fw) - pNull;
double strand_score = Math.max(lod_fw - lod, lod_bw - lod);
return strand_score;
}
GenotypeLikelihoods HardyWeinberg(double[] allele_likelihoods)
{
GenotypeLikelihoods G = new GenotypeLikelihoods();
int k = 0;
for (int i = 0; i < 4; i++)
{
for (int j = i; j < 4; j++)
{
G.likelihoods[k] = allele_likelihoods[i] * allele_likelihoods[j];
k++;
}
}
return G;
}
char PickAlt(char ref, double[] allele_likelihoods)
{
Integer[] perm = Utils.SortPermutation(allele_likelihoods);
if (perm[3] != BaseUtils.simpleBaseToBaseIndex(ref)) { return BaseUtils.baseIndexToSimpleBase(perm[3]); }
else { return BaseUtils.baseIndexToSimpleBase(perm[2]); }
}
double Compute_discovery_lod(char ref, GenotypeLikelihoods[] genotype_likelihoods)
{
double pBest = 0;
double pRef = 0;
for (int i = 0; i < genotype_likelihoods.length; i++)
{
pBest += genotype_likelihoods[i].BestPosterior();
pRef += genotype_likelihoods[i].RefPosterior(ref);
}
return pBest - pRef;
}
// this one is a bit of a lazy hack.
double Compute_alt_freq(char ref, double[] allele_likelihoods)
{
return allele_likelihoods[BaseUtils.simpleBaseToBaseIndex(PickAlt(ref, allele_likelihoods))];
}
int Compute_n_ref(char ref, GenotypeLikelihoods[] genotype_likelihoods)
{
int n = 0;
for (int i = 0; i < genotype_likelihoods.length; i++)
{
if (genotype_likelihoods[i].coverage == 0) { continue; }
String g = genotype_likelihoods[i].BestGenotype();
if ((g.charAt(0) == ref) && (g.charAt(1) == ref)) { n += 1; }
}
return n;
}
int Compute_n_het(char ref, GenotypeLikelihoods[] genotype_likelihoods)
{
int n = 0;
for (int i = 0; i < genotype_likelihoods.length; i++)
{
if (genotype_likelihoods[i].coverage == 0) { continue; }
String g = genotype_likelihoods[i].BestGenotype();
if ((g.charAt(0) == ref) && (g.charAt(1) != ref)) { n += 1; }
if ((g.charAt(0) != ref) && (g.charAt(1) == ref)) { n += 1; }
}
return n;
}
int Compute_n_hom(char ref, GenotypeLikelihoods[] genotype_likelihoods)
{
int n = 0;
for (int i = 0; i < genotype_likelihoods.length; i++)
{
if (genotype_likelihoods[i].coverage == 0) { continue; }
String g = genotype_likelihoods[i].BestGenotype();
if ((g.charAt(0) != ref) && (g.charAt(1) != ref)) { n += 1; }
}
return n;
}
// This should actually return a GLF Record
String MultiSampleCall(LocusContext context, List<String> sample_names)
{
LocusContext[] contexts = filterLocusContextBySample(context, sample_names, 0);
double lod = LOD(contexts);
double strand_score = StrandScore(context);
EM_Result em_result = EM(contexts);
GenotypeLikelihoods population_genotype_likelihoods = HardyWeinberg(em_result.allele_likelihoods);
double pD = Compute_pD(em_result.genotype_likelihoods);
double pNull = Compute_pNull(contexts);
double discovery_lod = Compute_discovery_lod(ref, em_result.genotype_likelihoods);
double alt_freq = Compute_alt_freq(ref, em_result.allele_likelihoods);
char alt = 'N';
if (lod > 0.0) { alt = PickAlt(ref, em_result.allele_likelihoods); }
int n_ref = Compute_n_ref(ref, em_result.genotype_likelihoods);
int n_het = Compute_n_het(ref, em_result.genotype_likelihoods);
int n_hom = Compute_n_hom(ref, em_result.genotype_likelihoods);
discovery_output_file.printf("%s %c %c %f %f %f %f %f %s ", context.getLocation(), ref, alt, lod, strand_score, pD, pNull, discovery_lod, in_dbsnp);
for (int i = 0; i < 4; i++) { discovery_output_file.printf("%f ", em_result.allele_likelihoods[i]); }
discovery_output_file.printf("%f %d %d %d %d %f %f %f %f %f %f\n", alt_freq, em_result.EM_N, n_ref, n_het, n_hom, pD_fw, pNull_fw, EM_alt_freq_fw, pD_bw, pNull_bw, EM_alt_freq_bw);
for (int i = 0; i < em_result.genotype_likelihoods.length; i++)
{
individual_output_file.printf("%s %c %s ", context.getLocation(), ref, sample_names.get(i));
individual_output_file.printf("%s %f %f %s ", em_result.genotype_likelihoods[i].BestGenotype(),
em_result.genotype_likelihoods[i].LodVsNextBest(),
em_result.genotype_likelihoods[i].LodVsRef(ref),
in_dbsnp);
//individual_output.printf("%s ", new ReadBackedPileup(ref, contexts[i]).getBasePileupAsCountsString());
assert(em_result.genotype_likelihoods[i] != null);
em_result.genotype_likelihoods[i].sort();
assert(em_result.genotype_likelihoods[i].sorted_likelihoods != null);
for (int j = 0; j < em_result.genotype_likelihoods[i].sorted_likelihoods.length; j++)
{
individual_output_file.printf("%f ", em_result.genotype_likelihoods[i].likelihoods[j]);
}
individual_output_file.printf("\n");
}
return null;
}
// END Calling Functions
/////////
/////////
// Utility Functions
/// Filter a locus context by forward and backward
private LocusContext filterLocusContextByStrand(LocusContext context, String strand)
{
ArrayList<SAMRecord> reads = new ArrayList<SAMRecord>();
ArrayList<Integer> offsets = new ArrayList<Integer>();
for (int i = 0; i < context.getReads().size(); i++)
{
SAMRecord read = context.getReads().get(i);
Integer offset = context.getOffsets().get(i);
// Filter for strandedness
if ((!strand.contains("+")) && (read.getReadNegativeStrandFlag() == false)) { continue; }
if ((!strand.contains("-")) && (read.getReadNegativeStrandFlag() == true)) { continue; }
reads.add(read);
offsets.add(offset);
}
return new LocusContext(context.getLocation(), reads, offsets);
}
// Filter a locus context by sample ID
private LocusContext[] filterLocusContextBySample(LocusContext context, List<String> sample_names, int downsample)
{
HashMap<String,Integer> index = new HashMap<String,Integer>();
for (int i = 0; i < sample_names.size(); i++)
{
index.put(sample_names.get(i), i);
}
LocusContext[] contexts = new LocusContext[sample_names.size()];
ArrayList<SAMRecord>[] reads = new ArrayList[sample_names.size()];
ArrayList<Integer>[] offsets = new ArrayList[sample_names.size()];
for (int i = 0; i < sample_names.size(); i++)
{
reads[i] = new ArrayList<SAMRecord>();
offsets[i] = new ArrayList<Integer>();
}
for (int i = 0; i < context.getReads().size(); i++)
{
SAMRecord read = context.getReads().get(i);
Integer offset = context.getOffsets().get(i);
String RG = (String)(read.getAttribute("RG"));
assert(header != null);
assert(header.getReadGroup(RG) != null);
String sample = header.getReadGroup(RG).getSample();
if (SAMPLE_NAME_REGEX != null) { sample = sample.replaceAll(SAMPLE_NAME_REGEX, "$1"); }
reads[index.get(sample)].add(read);
offsets[index.get(sample)].add(offset);
}
if (downsample != 0)
{
for (int j = 0; j < reads.length; j++)
{
List<Integer> perm = new ArrayList<Integer>();
for (int i = 0; i < reads[j].size(); i++) { perm.add(i); }
perm = Utils.RandomSubset(perm, downsample);
ArrayList<SAMRecord> downsampled_reads = new ArrayList<SAMRecord>();
ArrayList<Integer> downsampled_offsets = new ArrayList<Integer>();
for (int i = 0; i < perm.size(); i++)
{
downsampled_reads.add(reads[j].get(perm.get(i)));
downsampled_offsets.add(offsets[j].get(perm.get(i)));
}
reads[j] = downsampled_reads;
offsets[j] = downsampled_offsets;
contexts[j] = new LocusContext(context.getLocation(), reads[j], offsets[j]);
}
}
else
{
for (int j = 0; j < reads.length; j++)
{
contexts[j] = new LocusContext(context.getLocation(), reads[j], offsets[j]);
}
}
return contexts;
}
// END Utility functions
/////////
}

259
java/src/org/broadinstitute/sting/playground/gatk/walkers/PoolCaller.java
View File

@ -9,9 +9,9 @@ import org.broadinstitute.sting.gatk.LocusContext;
import org.broadinstitute.sting.gatk.refdata.RefMetaDataTracker; import org.broadinstitute.sting.gatk.refdata.RefMetaDataTracker;
import org.broadinstitute.sting.gatk.walkers.LocusWalker; import org.broadinstitute.sting.gatk.walkers.LocusWalker;
import org.broadinstitute.sting.playground.utils.AlleleFrequencyEstimate; import org.broadinstitute.sting.playground.utils.AlleleFrequencyEstimate;
import org.broadinstitute.sting.utils.GenomeLoc; import org.broadinstitute.sting.utils.*;
import org.broadinstitute.sting.playground.utils.*;
import org.broadinstitute.sting.utils.ReadBackedPileup; import org.broadinstitute.sting.utils.ReadBackedPileup;
import org.broadinstitute.sting.utils.Utils;
import org.broadinstitute.sting.utils.cmdLine.Argument; import org.broadinstitute.sting.utils.cmdLine.Argument;
import java.util.*; import java.util.*;
@ -21,7 +21,7 @@ import java.io.*;
// Draft iterative pooled caller // Draft iterative pooled caller
// j.maguire 4-27-2009 // j.maguire 4-27-2009
public class PoolCaller extends LocusWalker<AlleleFrequencyEstimate, String> public class PoolCaller extends LocusWalker<AlleleFrequencyEstimate[], String[]>
{ {
List<SingleSampleGenotyper> callers = null; List<SingleSampleGenotyper> callers = null;
List<String> sample_names = null; List<String> sample_names = null;
@ -38,9 +38,6 @@ public class PoolCaller extends LocusWalker<AlleleFrequencyEstimate, String>
private PrintStream discovery_output_file; private PrintStream discovery_output_file;
private PrintStream individual_output_file; private PrintStream individual_output_file;
AlleleFrequencyEstimate[] calls;
ArrayList<String> caller_sums;
public void initialize() public void initialize()
{ {
try try
@ -59,15 +56,8 @@ public class PoolCaller extends LocusWalker<AlleleFrequencyEstimate, String>
this.header = toolkit.getEngine().getSAMHeader(); this.header = toolkit.getEngine().getSAMHeader();
List<SAMReadGroupRecord> read_groups = header.getReadGroups(); List<SAMReadGroupRecord> read_groups = header.getReadGroups();
/*
GenomeAnalysisEngine toolkit = this.getToolkit();
SAMFileHeader header = toolkit.getSamReader().getFileHeader();
List<SAMReadGroupRecord> read_groups = header.getReadGroups();
*/
sample_names = new ArrayList<String>(); sample_names = new ArrayList<String>();
callers = new ArrayList<SingleSampleGenotyper>(); callers = new ArrayList<SingleSampleGenotyper>();
caller_sums = new ArrayList<String>();
random = new Random(42); random = new Random(42);
@ -93,12 +83,11 @@ public class PoolCaller extends LocusWalker<AlleleFrequencyEstimate, String>
caller.SAMPLE_NAME_REGEX = SAMPLE_NAME_REGEX; caller.SAMPLE_NAME_REGEX = SAMPLE_NAME_REGEX;
caller.initialize(); caller.initialize();
caller.variantsOut = individual_output_file; caller.variantsOut = individual_output_file;
caller_sums.add(caller.reduceInit());
callers.add(caller); callers.add(caller);
} }
} }
public AlleleFrequencyEstimate map(RefMetaDataTracker tracker, char ref, LocusContext context) public AlleleFrequencyEstimate[] map(RefMetaDataTracker tracker, char ref, LocusContext context)
{ {
if (ref == 'N') { return null; } if (ref == 'N') { return null; }
ref = Character.toUpperCase(ref); ref = Character.toUpperCase(ref);
@ -110,66 +99,151 @@ public class PoolCaller extends LocusWalker<AlleleFrequencyEstimate, String>
if (forward.getReads().size() == 0) { return null; } if (forward.getReads().size() == 0) { return null; }
if (backward.getReads().size() == 0) { return null; } if (backward.getReads().size() == 0) { return null; }
AlleleFrequencyEstimate estimate_both = EM(tracker, ref, context); // Pick the alternate base
AlleleFrequencyEstimate estimate_forward = EM(tracker, ref, forward); char alt = 'N';
AlleleFrequencyEstimate estimate_backward = EM(tracker, ref, backward); {
EM_Result result_both = EM(tracker, ref, context, -1, 'N', 1, lodThreshold, callers);
int[] counts = new int[4];
if (result_both.individuals == null) { return null; }
for (int i = 0; i < result_both.individuals.length; i++)
{
if (result_both.individuals[i] == null) { continue; }
if (result_both.individuals[i].lodVsRef >= lodThreshold)
{
counts[BaseUtils.simpleBaseToBaseIndex(result_both.individuals[i].alt)] += 1;
}
Integer[] perm = Utils.SortPermutation(counts);
alt = BaseUtils.baseIndexToSimpleBase(perm[3]);
}
}
discovery_output_file.printf("%s %c %f %c %f\n", double EM_alt_freq;
if (MAX_ITERATIONS == 1) { EM_alt_freq = -1; }
else { EM_alt_freq = 0.5; }
EM_Result result_both = EM(tracker, ref, context, EM_alt_freq, alt, MAX_ITERATIONS, lodThreshold, callers);
EM_Result result_forward = EM(tracker, ref, forward, EM_alt_freq, alt, MAX_ITERATIONS, lodThreshold, callers);
EM_Result result_backward = EM(tracker, ref, backward, EM_alt_freq, alt, MAX_ITERATIONS, lodThreshold, callers);
EM_Result null_both = EM(tracker, ref, context, 0, alt, 1, 1e-3, callers);
EM_Result null_forward = EM(tracker, ref, forward, 0, alt, 1, 1e-3, callers);
EM_Result null_backward = EM(tracker, ref, backward, 0, alt, 1, 1e-3, callers);
if (result_both.pool == null) { return null; }
AlleleFrequencyEstimate estimate_both = result_both.pool;
double lod_forward;
double lod_backward;
double lod_both;
double strand_score;
char forward_alt;
char backward_alt;
if ((result_forward.pool == null) ||
(result_backward.pool == null) ||
(null_both == null) ||
(null_forward == null) ||
(null_backward == null))
{
lod_forward = 0;
lod_backward = 0;
lod_both = 0;
strand_score = 0;
forward_alt = 'N';
backward_alt = 'N';
}
else
{
AlleleFrequencyEstimate estimate_forward = result_forward.pool;
AlleleFrequencyEstimate estimate_backward = result_backward.pool;
double p_D_both = 0;
double p_D_forward = 0;
double p_D_backward = 0;
double p_D_null_both = 0;
double p_D_null_forward = 0;
double p_D_null_backward = 0;
for (int i = 0; i < result_both.individuals.length; i++)
{
double sum_both = 0;
double sum_forward = 0;
double sum_backward = 0;
double sum_null_both = 0;
double sum_null_forward = 0;
double sum_null_backward = 0;
for (int j = 0; j < result_both.individuals[i].genotypeLikelihoods.likelihoods.length; j++)
{
sum_both += Math.pow(10, result_both.individuals[i].genotypeLikelihoods.likelihoods[j]);
sum_forward += Math.pow(10, result_forward.individuals[i].genotypeLikelihoods.likelihoods[j]);
sum_backward += Math.pow(10, result_backward.individuals[i].genotypeLikelihoods.likelihoods[j]);
sum_null_both += Math.pow(10, null_both.individuals[i].genotypeLikelihoods.likelihoods[j]);
sum_null_forward += Math.pow(10, null_forward.individuals[i].genotypeLikelihoods.likelihoods[j]);
sum_null_backward += Math.pow(10, null_backward.individuals[i].genotypeLikelihoods.likelihoods[j]);
}
p_D_both += Math.log10(sum_both);
p_D_forward += Math.log10(sum_forward);
p_D_backward += Math.log10(sum_backward);
p_D_null_both += Math.log10(sum_null_both);
p_D_null_forward += Math.log10(sum_null_forward);
p_D_null_backward += Math.log10(sum_null_backward);
}
forward_alt = estimate_forward.alt;
backward_alt = estimate_backward.alt;
lod_forward = (p_D_forward + p_D_null_backward) - p_D_null_both;
lod_backward = (p_D_backward + p_D_null_backward) - p_D_null_both;
lod_both = p_D_both - p_D_null_both;
strand_score = Math.max(lod_forward - lod_both, lod_backward - lod_both);
}
System.out.printf("DBG %s %f %f %f %f\n", context.getLocation(), result_both.pool.pBest, null_both.pool.pBest, result_both.pool.pRef, null_both.pool.pBest);
discovery_output_file.printf("%s %c %c %f\n",
estimate_both.asPoolTabularString(), estimate_both.asPoolTabularString(),
estimate_forward.alt, forward_alt,
estimate_forward.lodVsRef, backward_alt,
estimate_backward.alt, strand_score);
estimate_backward.lodVsRef);
//discovery_output_file.printf("%s\n", estimate_forward.asPoolTabularString());
//discovery_output_file.printf("%s\n", estimate_backward.asPoolTabularString());
//discovery_output_file.printf("\n");
return null; return result_both.individuals;
} }
private AlleleFrequencyEstimate EM(RefMetaDataTracker tracker, char ref, LocusContext context) private class EM_Result
{
AlleleFrequencyEstimate pool;
AlleleFrequencyEstimate[] individuals;
public EM_Result(AlleleFrequencyEstimate pool, AlleleFrequencyEstimate[] individuals)
{
this.pool = pool;
this.individuals = individuals;
}
// Construct an EM_Result that indicates no data.
public EM_Result()
{
this.pool = null;
this.individuals = null;
}
}
private EM_Result EM(RefMetaDataTracker tracker, char ref, LocusContext context, double EM_alt_freq, char alt, int MAX_ITERATIONS, double lodThreshold, List<SingleSampleGenotyper> callers)
{ {
if (context.getReads().size() == 0) { return null; } if (context.getReads().size() == 0) { return null; }
LocusContext[] contexts = filterLocusContext(context, sample_names, 0); LocusContext[] contexts = filterLocusContext(context, sample_names, 0);
// EM Loop: // EM Loop:
double EM_alt_freq;
double EM_N = 0; double EM_N = 0;
calls = null; AlleleFrequencyEstimate[] calls = null;
// this line is kinda hacky
if (MAX_ITERATIONS == 1) { EM_alt_freq = -1; }
else { EM_alt_freq = 0.5; }
// (this loop is the EM cycle) // (this loop is the EM cycle)
double[] trajectory = new double[MAX_ITERATIONS + 1]; trajectory[0] = EM_alt_freq; double[] trajectory = new double[MAX_ITERATIONS + 1]; trajectory[0] = EM_alt_freq;
double[] likelihood_trajectory = new double[MAX_ITERATIONS + 1]; likelihood_trajectory[0] = 0.0; double[] likelihood_trajectory = new double[MAX_ITERATIONS + 1]; likelihood_trajectory[0] = 0.0;
boolean is_a_snp = false; boolean is_a_snp = false;
// Pick the alternate base
char alt = 'N';
{
ReadBackedPileup pileup = new ReadBackedPileup(ref, context);
String bases = pileup.getBases();
int A = 0;
int C = 0;
int G = 0;
int T = 0;
int max_count = -1;
for (int i = 0; i < bases.length(); i++)
{
char b = bases.charAt(i);
if (b == ref) { continue; }
switch (b)
{
case 'A' : A += 1; if (A > max_count) { max_count = A; alt = 'A'; } break;
case 'C' : C += 1; if (C > max_count) { max_count = C; alt = 'C'; } break;
case 'G' : G += 1; if (G > max_count) { max_count = G; alt = 'G'; } break;
case 'T' : T += 1; if (T > max_count) { max_count = T; alt = 'T'; } break;
}
}
}
for (int iterations = 0; iterations < MAX_ITERATIONS; iterations++) for (int iterations = 0; iterations < MAX_ITERATIONS; iterations++)
{ {
// 6. Re-call from shallow coverage using the estimated frequency as a prior, // 6. Re-call from shallow coverage using the estimated frequency as a prior,
@ -193,12 +267,11 @@ public class PoolCaller extends LocusWalker<AlleleFrequencyEstimate, String>
if (! FRACTIONAL_COUNTS) if (! FRACTIONAL_COUNTS)
{ {
//System.out.printf("DBG: %s %f %f\n", if (Math.abs(calls[i].lodVsRef) >= lodThreshold)
// context.getLocation(), {
// calls[i].lodVsNextBest, EM_sum += calls[i].emperical_allele_frequency() * calls[i].N;
// calls[i].lodVsRef); EM_N += calls[i].N;
EM_sum += calls[i].emperical_allele_frequency() * calls[i].N; }
EM_N += calls[i].N;
} }
else else
{ {
@ -218,14 +291,16 @@ public class PoolCaller extends LocusWalker<AlleleFrequencyEstimate, String>
if (likelihood_trajectory[iterations] == likelihood_trajectory[iterations+1]) { break; } if (likelihood_trajectory[iterations] == likelihood_trajectory[iterations+1]) { break; }
//System.out.printf("DBGTRAJ %s %f %f %f %f %f %f\n", /*
// context.getLocation(), System.out.printf("DBGTRAJ %s %f %f %f %f %f %f\n",
// EM_sum, context.getLocation(),
// EM_N, EM_sum,
// trajectory[iterations], EM_N,
// trajectory[iterations+1], trajectory[iterations],
// likelihood_trajectory[iterations], trajectory[iterations+1],
// likelihood_trajectory[iterations+1]); likelihood_trajectory[iterations],
likelihood_trajectory[iterations+1]);
*/
} }
// 7. Output some statistics. // 7. Output some statistics.
@ -246,9 +321,10 @@ public class PoolCaller extends LocusWalker<AlleleFrequencyEstimate, String>
{ {
if (calls[i].depth == 0) { continue; } if (calls[i].depth == 0) { continue; }
if (calls[i].lodVsRef < lodThreshold) { continue; }
discovery_likelihood += calls[i].pBest; discovery_likelihood += calls[i].pBest;
discovery_null += calls[i].pRef; discovery_null += calls[i].pRef;
//System.out.printf("DBG %f %f %c %s\n", calls[i].pBest, calls[i].pRef, ref, calls[i].bases);
if (calls[i].qhat == 0.0) { n_ref += 1; } if (calls[i].qhat == 0.0) { n_ref += 1; }
if (calls[i].qhat == 0.5) { n_het += 1; } if (calls[i].qhat == 0.5) { n_het += 1; }
@ -258,6 +334,8 @@ public class PoolCaller extends LocusWalker<AlleleFrequencyEstimate, String>
if (discovery_lod <= 0) { alt = 'N'; } if (discovery_lod <= 0) { alt = 'N'; }
//discovery_output_file.printf("%s %c %c %f %f %f %f %f %f %d %d %d\n", context.getLocation(), ref, alt, EM_alt_freq, discovery_likelihood, discovery_null, discovery_prior, discovery_lod, EM_N, n_ref, n_het, n_hom); //discovery_output_file.printf("%s %c %c %f %f %f %f %f %f %d %d %d\n", context.getLocation(), ref, alt, EM_alt_freq, discovery_likelihood, discovery_null, discovery_prior, discovery_lod, EM_N, n_ref, n_het, n_hom);
if (EM_N == 0) { return new EM_Result(); }
AlleleFrequencyEstimate estimate = new AlleleFrequencyEstimate(context.getLocation(), AlleleFrequencyEstimate estimate = new AlleleFrequencyEstimate(context.getLocation(),
ref, ref,
alt, alt,
@ -276,7 +354,7 @@ public class PoolCaller extends LocusWalker<AlleleFrequencyEstimate, String>
estimate.n_ref = n_ref; // HACK estimate.n_ref = n_ref; // HACK
estimate.n_het = n_het; // HACK estimate.n_het = n_het; // HACK
estimate.n_hom = n_hom; // HACK estimate.n_hom = n_hom; // HACK
return estimate; return new EM_Result(estimate, calls);
//for (int i = 0; i < likelihood_trajectory.length; i++) //for (int i = 0; i < likelihood_trajectory.length; i++)
@ -391,14 +469,7 @@ public class PoolCaller extends LocusWalker<AlleleFrequencyEstimate, String>
return contexts; return contexts;
} }
private void CollectStrandInformation(char ref, LocusContext context) public void onTraversalDone(String[] result)
{
List<SAMRecord> reads = context.getReads();
List<Integer> offsets = context.getOffsets();
}
public void onTraversalDone(String result)
{ {
try try
{ {
@ -411,32 +482,30 @@ public class PoolCaller extends LocusWalker<AlleleFrequencyEstimate, String>
{ {
e.printStackTrace(); e.printStackTrace();
} }
out.println("PoolCaller done.\n");
return; return;
} }
public String reduceInit() public String[] single_sample_reduce_sums = null;
public String[] reduceInit()
{ {
discovery_output_file.printf("loc ref alt EM_alt_freq discovery_likelihood discovery_null discovery_prior discovery_lod EM_N n_ref n_het n_hom fw_alt fw_lod bw_alt bw_lod\n"); discovery_output_file.printf("loc ref alt EM_alt_freq discovery_likelihood discovery_null discovery_prior discovery_lod EM_N n_ref n_het n_hom fw_alt bw_alt strand_score\n");
String[] single_sample_reduce_sums = new String[callers.size()];
for (int i = 0; i < callers.size(); i++) for (int i = 0; i < callers.size(); i++)
{ {
callers.get(i).reduceInit(); single_sample_reduce_sums[i] = callers.get(i).reduceInit();
} }
return ""; return single_sample_reduce_sums;
} }
public String reduce(AlleleFrequencyEstimate alleleFreq, String sum) public String[] reduce(AlleleFrequencyEstimate[] alleleFreqs, String[] sum)
{ {
if (calls == null) { return ""; } if (alleleFreqs == null) { return sum; }
for (int i = 0; i < callers.size(); i++) for (int i = 0; i < callers.size(); i++)
{ {
if (calls == null) { System.err.printf("calls == null\n"); } sum[i] = callers.get(i).reduce(alleleFreqs[i], sum[i]);
if (calls[i] == null) { System.err.printf("calls[%d] == null\n", i); }
if (caller_sums == null) { System.err.printf("caller_sums == null\n"); }
if (callers.get(i) == null) { System.err.printf("callers[%d] == null\n", i); }
if (caller_sums.get(i) == null) { System.err.printf("caller_sums[%d] == null\n", i); }
caller_sums.set(i, callers.get(i).reduce(calls[i], caller_sums.get(i)));
} }
return ""; return sum;
} }

14
java/src/org/broadinstitute/sting/playground/gatk/walkers/SingleSampleGenotyper.java
View File

@ -272,26 +272,12 @@ public class SingleSampleGenotyper extends LocusWalker<AlleleFrequencyEstimate,
this.alt_allele = alt; this.alt_allele = alt;
} }
// Given result of map function
private String confident_ref_interval_contig = "";
private long confident_ref_interval_start = 0;
private double confident_ref_interval_LOD_sum = 0;
private double confident_ref_interval_length = 0;
private long last_position_considered = -1;
private boolean inside_confident_ref_interval = false;
/** /**
* Initialize values appropriately for the reduce step. * Initialize values appropriately for the reduce step.
* *
* @return an empty string * @return an empty string
*/ */
public String reduceInit() { public String reduceInit() {
confident_ref_interval_contig = "";
confident_ref_interval_start = 0;
confident_ref_interval_LOD_sum = 0;
confident_ref_interval_length = 0;
last_position_considered = -1;
inside_confident_ref_interval = false;
return ""; return "";
} }

2
java/src/org/broadinstitute/sting/playground/utils/AlleleFrequencyEstimate.java
View File

@ -41,6 +41,8 @@ public class AlleleFrequencyEstimate {
public int n_het; public int n_het;
public int n_hom; public int n_hom;
public GenotypeLikelihoods genotypeLikelihoods = null;
GenomeLoc l; GenomeLoc l;

59
java/src/org/broadinstitute/sting/playground/utils/GenotypeLikelihoods.java
View File

@ -1,7 +1,6 @@
package org.broadinstitute.sting.playground.utils; package org.broadinstitute.sting.playground.utils;
import org.broadinstitute.sting.utils.GenomeLoc; import org.broadinstitute.sting.utils.*;
import org.broadinstitute.sting.utils.MathUtils;
import org.broadinstitute.sting.utils.Utils; import org.broadinstitute.sting.utils.Utils;
import org.broadinstitute.sting.utils.QualityUtils; import org.broadinstitute.sting.utils.QualityUtils;
@ -39,6 +38,7 @@ public class GenotypeLikelihoods {
public double[] likelihoods; public double[] likelihoods;
public String[] genotypes; public String[] genotypes;
public int coverage;
// The genotype priors; // The genotype priors;
private double priorHomRef; private double priorHomRef;
@ -76,6 +76,9 @@ public class GenotypeLikelihoods {
likelihoods = new double[10]; likelihoods = new double[10];
genotypes = new String[10]; genotypes = new String[10];
coverage = 0;
for (int i = 0; i < likelihoods.length; i++) { likelihoods[i] = Math.log10(0.1); }
genotypes[0] = "AA"; genotypes[0] = "AA";
genotypes[1] = "AC"; genotypes[1] = "AC";
@ -150,9 +153,21 @@ public class GenotypeLikelihoods {
} }
} }
public void add(char ref, char read, byte qual) { public void add(char ref, char read, byte qual)
for (int i = 0; i < genotypes.length; i++) { {
likelihoods[i] += calculateAlleleLikelihood(ref, read, genotypes[i], qual); if (coverage == 0)
{
for (int i = 0; i < likelihoods.length; i++)
{
likelihoods[i] = 0;
}
}
double sum = 0.0;
for (int i = 0; i < genotypes.length; i++)
{
double likelihood = calculateAlleleLikelihood(ref, read, genotypes[i], qual);
likelihoods[i] += likelihood;
coverage += 1;
} }
} }
@ -197,16 +212,40 @@ public class GenotypeLikelihoods {
public String toString(char ref) { public String toString(char ref) {
this.sort(); this.sort();
double sum = 0;
String s = String.format("%s %f %f ", this.BestGenotype(), this.LodVsNextBest(), this.LodVsRef(ref)); String s = String.format("%s %f %f ", this.BestGenotype(), this.LodVsNextBest(), this.LodVsRef(ref));
for (int i = 0; i < sorted_genotypes.length; i++) { for (int i = 0; i < sorted_genotypes.length; i++) {
if (i != 0) { if (i != 0) {
s = s + " "; s = s + " ";
} }
s = s + sorted_genotypes[i] + ":" + String.format("%.2f", sorted_likelihoods[i]); s = s + sorted_genotypes[i] + ":" + String.format("%.2f", sorted_likelihoods[i]);
sum += Math.pow(10,sorted_likelihoods[i]);
} }
s = s + String.format(" %f", sum);
return s; return s;
} }
public void ApplyPrior(char ref, double[] allele_likelihoods)
{
int k = 0;
for (int i = 0; i < 4; i++)
{
for (int j = i; j < 4; j++)
{
if (i == j)
{
this.likelihoods[k] += Math.log10(allele_likelihoods[i]) + Math.log10(allele_likelihoods[j]);
}
else
{
this.likelihoods[k] += Math.log10(allele_likelihoods[i]) + Math.log10(allele_likelihoods[j]) + Math.log10(2);
}
k++;
}
}
this.sort();
}
public void ApplyPrior(char ref, char alt, double p_alt) { public void ApplyPrior(char ref, char alt, double p_alt) {
for (int i = 0; i < genotypes.length; i++) { for (int i = 0; i < genotypes.length; i++) {
if ((p_alt == -1) || (p_alt <= 1e-6)) { if ((p_alt == -1) || (p_alt <= 1e-6)) {
@ -317,6 +356,12 @@ public class GenotypeLikelihoods {
return this.sorted_likelihoods[0]; return this.sorted_likelihoods[0];
} }
public double RefPosterior(char ref)
{
this.LodVsRef(ref);
return this.ref_likelihood;
}
public AlleleFrequencyEstimate toAlleleFrequencyEstimate(GenomeLoc location, char ref, int depth, String bases, double[] posteriors, String sample_name) { public AlleleFrequencyEstimate toAlleleFrequencyEstimate(GenomeLoc location, char ref, int depth, String bases, double[] posteriors, String sample_name) {
this.sort(); this.sort();
double qhat = Double.NaN; double qhat = Double.NaN;
@ -349,6 +394,8 @@ public class GenotypeLikelihoods {
this.LodVsRef(ref); //HACK this.LodVsRef(ref); //HACK
//System.out.printf("DBG: %f %f\n", sorted_likelihoods[0], ref_likelihood); //System.out.printf("DBG: %f %f\n", sorted_likelihoods[0], ref_likelihood);
return new AlleleFrequencyEstimate(location, ref, alt, 2, qhat, qstar, this.LodVsRef(ref), this.LodVsNextBest(), sorted_likelihoods[0], ref_likelihood, depth, bases, null, this.likelihoods, sample_name); AlleleFrequencyEstimate AFE = new AlleleFrequencyEstimate(location, ref, alt, 2, qhat, qstar, this.LodVsRef(ref), this.LodVsNextBest(), sorted_likelihoods[0], ref_likelihood, depth, bases, (double[][]) null, this.likelihoods, sample_name);
AFE.genotypeLikelihoods = this;
return AFE;
} }
} }

17
java/src/org/broadinstitute/sting/utils/ReadBackedPileup.java
View File

@ -79,6 +79,23 @@ public class ReadBackedPileup extends BasicPileup {
return secondaryQualPileupAsString(reads, offsets); return secondaryQualPileupAsString(reads, offsets);
} }
public String getBasePileupAsCountsString() {
String bases = basePileupAsString(reads, offsets);
int[] counts = new int[4];
for (int i = 0; i < reads.size(); i++)
{
char base = Character.toUpperCase((char)(reads.get(i).getReadBases()[offsets.get(i)]));
if (BaseUtils.simpleBaseToBaseIndex(base) == -1) { continue; }
counts[BaseUtils.simpleBaseToBaseIndex(base)]++;
}
return String.format("A[%d] C[%d] G[%d] T[%d]",
counts[0],
counts[1],
counts[2],
counts[3]);
}
public String getProbDistPileup() { public String getProbDistPileup() {
return probDistPileupAsString(reads, offsets); return probDistPileupAsString(reads, offsets);
} }