HaplotypeProbabilityOfNormalGivenTumor.java

/*
 * The MIT License
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 * Copyright (c) 2016 The Broad Institute
 *
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 * IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,
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package picard.fingerprint;

/**
 * A wrapper class for any HaplotypeProbabilities instance that will assume that the given evidence is that of a tumor sample and
 * provide an hp for the normal sample that tumor came from. This models possible loss of hetrozygosity where het genotypes
 * turn into a homozygous genotype with probability pLoH.
 *
 * The shortcoming of this model is that we assume that the events are all independent, but this way they are allowed.
 *
 * @author farjoun
 */

public class HaplotypeProbabilityOfNormalGivenTumor extends HaplotypeProbabilities {

    private final double[][] transitionMatrix;
    private final HaplotypeProbabilities hpOfTumor;

    public HaplotypeProbabilityOfNormalGivenTumor(final HaplotypeProbabilities hpOfTumor, final double pLoH) {
        super(hpOfTumor.getHaplotype());

        this.hpOfTumor = hpOfTumor;
        transitionMatrix = new double[][]{
                //This is P(g_t|g_n)
                //tumor genotype are the columns.
                {1,               0,        0},  //normal is hom_ref => tumor must be the same
                {pLoH / 2, 1 - pLoH, pLoH / 2},  //normal is het     => tumor may have transitioned
                {0,               0,        1}}; //normal is hom_var => tumor must be the same
    }

    // This function needs to be overridden since we want likelihood to mean the probability of the
    // data given a particular _normal_ genotype, however, the likelihood as given is that where the
    // genotype is of the tumor (if that's what the data was measuring)

    // P(D_t|g_n) = \sum_{g_t}  P(D_t|g_t,g_n)
    //            = \sum P(D_t|g_t, g_n) P(g_t|g_n)
    //            = \sum P(D_t|g_t) P(g_t|g_n)
    //            = hpOfTumor.getLikelihoods() * transitionMatrix
    // where the * operator is understood as linear algebra operation.

    @Override
    public double[] getLikelihoods() {
        final double[] normalHaplotypeLikelihoods = new double[3];
        final double[] tumorHaplotypeLikelihoods = hpOfTumor.getLikelihoods();
        for (final Genotype g_n : Genotype.values()) {
            normalHaplotypeLikelihoods[g_n.v] = 0D;
            for (final Genotype g_t : Genotype.values()) {
                normalHaplotypeLikelihoods[g_n.v] += tumorHaplotypeLikelihoods[g_t.v] * transitionMatrix[g_n.v][g_t.v];
            }
        }
        return normalHaplotypeLikelihoods;
    }

    @Override
    public Snp getRepresentativeSnp() {
        return hpOfTumor.getRepresentativeSnp();
    }

    @Override
    public void merge(final HaplotypeProbabilities ignored) {
        throw new IllegalArgumentException("Cannot merge HaplotypeProbabilityOfNormalGivenTumor. Merge the underlying object and create a new wrapper.");
    }

    @Override
    public int getObsAllele1() {
        return hpOfTumor.getObsAllele1();
    }

    @Override
    public int getObsAllele2() {
        return hpOfTumor.getObsAllele2();
    }

    @Override
    public int getTotalObs() {
        return hpOfTumor.getTotalObs();
    }

    @Override
    public boolean hasEvidence() {
        return hpOfTumor.hasEvidence();
    }
}