AlleleBalanceFilter.java

/*
 * The MIT License
 *
 * Copyright (c) 2014 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
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 * THE SOFTWARE.
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package picard.vcf.filter;

import htsjdk.samtools.util.CollectionUtil;
import htsjdk.variant.variantcontext.Allele;
import htsjdk.variant.variantcontext.Genotype;
import htsjdk.variant.variantcontext.GenotypesContext;
import htsjdk.variant.variantcontext.VariantContext;
import htsjdk.variant.variantcontext.VariantContextUtils;
import htsjdk.variant.vcf.VCFFilterHeaderLine;

import java.util.HashMap;
import java.util.List;
import java.util.Map;

/**
 * Filters out a record if the allele balance for heterozygotes is out of a defined range across all samples.
 * The threshold is set as the minimum fraction of the data drawn from the less-represented allele - e.g. 0.3 would
 * set that whichever allele has lower representation across all heterozygous individuals must account for at least 30% of the
 * total observations.
 */
public class AlleleBalanceFilter implements VariantFilter {
    /** The filter string used for sites that fail the allele balance filter. */
    public static final String AB_FILTER = "AlleleBalance";

    private final double hetAlleleBalance;

    public AlleleBalanceFilter(final double hetAlleleBalance) {
        this.hetAlleleBalance = hetAlleleBalance;
    }

    private static class Counts { int samples; int allele1; int allele2; }

    @Override
    public List<VCFFilterHeaderLine> headerLines() {
        return CollectionUtil.makeList(new VCFFilterHeaderLine(AB_FILTER, "Heterozygote allele balance below required threshold."));
    }

    @Override
    public String filter(final VariantContext ctx) {
        if (ctx.getHetCount() == 0) return null;
        final Map<List<Allele>, Counts> countsMap = new HashMap<List<Allele>, Counts>();

        for (final Genotype gt : ctx.getGenotypesOrderedByName()) {
            if (gt.isNoCall() || !gt.isHet()) continue;

            final List<Allele> alleles = gt.getAlleles();
            Counts counts = countsMap.get(alleles);
            if (counts == null) {
                counts = new Counts();
                countsMap.put(alleles, counts);
            }

            counts.allele1 += gt.getAD()[ctx.getAlleleIndex(alleles.get(0))];
            counts.allele2 += gt.getAD()[ctx.getAlleleIndex(alleles.get(1))];
        }

        for (final Counts counts : countsMap.values()) {
            final int total = counts.allele1 + counts.allele2;
            if (total > 0 && Math.min(counts.allele1, counts.allele2) / (double) total < this.hetAlleleBalance) return AB_FILTER;
        }

        return null;
    }
}