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/*
* Copyright (C) 2014-2021 Brian L. Browning
*
* This file is part of Beagle
*
* Beagle is free software: you can redistribute it and/or modify
* it under the terms of the GNU General Public License as published by
* the Free Software Foundation, either version 3 of the License, or
* (at your option) any later version.
*
* Beagle is distributed in the hope that it will be useful,
* but WITHOUT ANY WARRANTY; without even the implied warranty of
* MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the
* GNU General Public License for more details.
*
* You should have received a copy of the GNU General Public License
* along with this program. If not, see <http://www.gnu.org/licenses/>.
*/
package phase;
import blbutil.BitArray;
import blbutil.DoubleArray;
import ints.IntArray;
import ints.IntList;
import java.util.Arrays;
import java.util.stream.IntStream;
import java.util.stream.Stream;
import vcf.Markers;
/**
* <p>Each instance of class {@code SamplePhase} stores an estimated haplotype
* pair for a sample, the list of markers with missing genotypes for the sample,
* a list of markers whose genotype phase with respect to the preceding
* heterozygote genotype is considered to be uncertain for the sample, and
* a set of marker clusters for the sample.
* </p>
* <p>Instances of class {@code SamplePhase} are not thread-safe.
* </p>
*
* @author Brian L. Browning {@code <browning@uw.edu>}
*/
public final class SamplePhase {
private final Markers markers;
private BitArray hap1;
private BitArray hap2;
private IntArray unphased;
private final IntArray missing;
private final byte[] clustSize;
/**
* Constructs a new {@code SamplePhase} instance from the specified data.
* @param markers the list of markers
* @param genPos the genetic positions of the specifed markers
* @param hap1 the list of alleles on the first haplotype
* @param hap2 the list of alleles on the second haplotype
* @param unphased the indices of markers whose genotype phase with respect
* to the preceding heterozygote is unknown
* @param missing the indices of markers whose genotype is missing
* @throws IllegalArgumentException if
* {@code genPos.size() != markers.nMarkers()}
* @throws IllegalArgumentException if
* {@code hap1.length != markers.nMarkers()
* || hap2.length != markers.nMarkers()}
* @throws IllegalArgumentException if the specified {@code unphased} or
* {@code missing} list is not a strictly increasing list of
* marker indices between 0 (inclusive) and {@code markers.nMarkers()}
* (exclusive)
* @throws NullPointerException if any argument is {@code null}
*/
public SamplePhase(Markers markers, DoubleArray genPos,
int[] hap1, int[] hap2, IntArray unphased, IntArray missing) {
int nMarkers = markers.size();
if (nMarkers!=genPos.size()) {
throw new IllegalArgumentException(String.valueOf(genPos.size()));
}
if (hap1.length!=nMarkers) {
throw new IllegalArgumentException(String.valueOf(hap1.length));
}
if (hap2.length!=nMarkers) {
throw new IllegalArgumentException(String.valueOf(hap2.length));
}
checkIncreasing(unphased, nMarkers);
checkIncreasing(missing, nMarkers);
this.markers = markers;
this.hap1 = new BitArray(markers.sumHapBits());
this.hap2 = new BitArray(markers.sumHapBits());
markers.allelesToBits(hap1, this.hap1);
markers.allelesToBits(hap2, this.hap2);
this.unphased = unphased;
this.missing = missing;
float maxClusterCM = 0.005f;
this.clustSize = clustSize(hap1, hap2, missing, genPos, maxClusterCM);
}
private static void checkIncreasing(IntArray ia, int nMarkers) {
int last = -1;
for (int j=0, n=ia.size(); j<n; ++j) {
if (ia.get(j)<=last) {
throw new IllegalArgumentException(ia.toString());
}
last = ia.get(j);
}
if (last>=nMarkers) {
throw new IllegalArgumentException(ia.toString());
}
}
private static byte[] clustSize(int[] hap1, int[] hap2, IntArray missing,
DoubleArray genPos, float maxCM) {
IntList clustSizes = new IntList(1<<12);
int nMarkers = genPos.size();
double maxClustEnd = genPos.get(0) + maxCM;
boolean prevIsMissOrHet = false;
int lastEnd = 0;
int missIndex = 0;
int nextMiss = missIndex<missing.size() ? missing.get(missIndex++) : -1;
for (int m=0; m<nMarkers; ++m) {
int size = m - lastEnd;
boolean isMissing = m==nextMiss;
if (isMissing) {
nextMiss = missIndex<missing.size() ? missing.get(missIndex++) : -1;
}
boolean isMissOrHet = isMissing || hap1[m]!=hap2[m];
if (prevIsMissOrHet || isMissOrHet || genPos.get(m)>maxClustEnd || size==255) {
if (m>0) {
clustSizes.add(size);
maxClustEnd = genPos.get(m) + maxCM;
lastEnd = m;
}
}
prevIsMissOrHet = isMissOrHet;
}
clustSizes.add(nMarkers - lastEnd);
return toByteArray(clustSizes);
}
private static byte[] toByteArray(IntList intList) {
byte[] ba = new byte[intList.size()];
for (int j=0; j<ba.length; ++j) {
ba[j] = (byte) intList.get(j);
}
return ba;
}
/**
* Returns the (exclusive) end marker indices of each marker cluster.
* The returned list is sorted in increasing order.
* @return the (exclusive) end marker indices of each marker cluster
*/
public int[] clustEnds() {
int[] clustEnds = new int[clustSize.length];
int cumSum = 0;
for (int j=0; j<clustSize.length; ++j) {
cumSum += (clustSize[j] & 0xff); // convert unsigned byte to integer
clustEnds[j] = cumSum;
}
return clustEnds;
}
/**
* Returns the list of markers.
* @return the list of markers
*/
public Markers markers() {
return markers;
}
/**
* Returns a list of marker indices in increasing order for which
* the genotype is missing.
* @return a list of marker indices in increasing order for which
* the genotype is missing
*/
public IntArray missing() {
return missing;
}
/**
* Returns a list of marker indices in increasing order whose genotype
* phase with respect to the preceding non-missing heterozygote genotype
* is unknown.
* @return a list of markers indices in increasing order whose genotype
* phase with respect to the preceding non-missing heterozygote genotype
* is unknown
*/
public IntArray unphased() {
return unphased;
}
/**
* Sets the list of markers whose genotype phase with respect to
* the preceding non-missing heterozygote genotype is unknown.
* @param unphased a list of markers whose genotype phase with respect to
* the preceding non-missing heterozygote genotype is unknown
* @throws IllegalArgumentException if the specified list or marker
* indices is not a strictly increasing list of indices between 0
* (inclusive) and {@code this.markers().nMarkers()} (exclusive)
* @throws NullPointerException if {@code unphased == null}
*/
public void setUnphased(IntArray unphased) {
checkIncreasing(unphased, markers.size());
this.unphased = unphased;
}
/**
* Copies the stored haplotypes to the specified {@code BitList} objects
* @param hap1 a {@code BitList} in which the sample's first haplotype's
* alleles will be stored
* @param hap2 a {@code BitList} in which the sample's second haplotype's
* alleles will be stored
* @throws IllegalArgumentException if
* {@code hap1.size() != this.markers().sumHaplotypeBits()}
* @throws IllegalArgumentException if
* {@code hap2.size()!= this.markers().sumHaplotypeBits()}
* @throws NullPointerException if {@code hap1 == null || hap2 == null}
*/
public void getHaps(BitArray hap1, BitArray hap2) {
int nBits = markers.sumHapBits();
if (hap1.size() != nBits || hap2.size() != nBits) {
throw new IllegalArgumentException("inconsistent data");
}
hap1.copyFrom(this.hap1, 0, this.hap1.size());
hap2.copyFrom(this.hap2, 0, this.hap2.size());
}
/**
* Returns the allele on the first haplotype for the specified marker.
* @param marker the marker index
* @return the allele on the first haplotype for the specified marker
* @throws IndexOutOfBoundsException if
* {@code marker < 0 || marker >= this.markers().nMarkers()}
*/
public int allele1(int marker) {
return markers.allele(hap1, marker);
}
/**
* Returns the allele on the second haplotype for the specified marker.
* @param marker the marker index
* @return the allele on the second haplotype for the specified marker
* @throws IndexOutOfBoundsException if
* {@code marker < 0 || marker >= this.markers().nMarkers()}
*/
public int allele2(int marker) {
return markers.allele(hap2, marker);
}
/**
* Sets the allele on the first haplotype for the specified marker
* to the specified allele
* @param marker the marker index
* @param allele the allele
* @throws IndexOutOfBoundsException if
* {@code marker < 0 || marker >= this.markers().nMarkers()}
* @throws IndexOutOfBoundsException if
* {@code allele < 0 || allele >= this.markers().marker(marker).nAlleles()}
*/
public void setAllele1(int marker, int allele) {
markers.setAllele(marker, allele, hap1);
}
/**
* Sets the allele on the second haplotype for the specified marker
* to the specified allele
* @param marker the marker index
* @param allele the allele
* @throws IndexOutOfBoundsException if
* {@code marker < 0 || marker >= this.markers().nMarkers()}
* @throws IndexOutOfBoundsException if
* {@code allele < 0 || allele >= this.markers().marker(marker).nAlleles()}
*/
public void setAllele2(int marker, int allele) {
markers.setAllele(marker, allele, hap2);
}
/**
* Swaps the alleles of the two haplotypes in the specified range of
* markers.
* @param start the start marker index (inclusive)
* @param end the end marker index (exclusive)
* @throws IndexOutOfBoundsException if
* {@code start < 0 || start > end || start >= this.markers().nMarkers()}
*/
public void swapHaps(int start, int end) {
int startBit = markers.sumHapBits(start);
int endBit = markers.sumHapBits(end);
BitArray.swapBits(hap1, hap2, startBit, endBit);
}
/**
* Returns the first haplotype. The haplotype is encoded with the
* {@code this.markers().allelesToBits()} method.
* @return the first haplotype
*/
public BitArray hap1() {
return new BitArray(this.hap1);
}
/**
* Returns the second haplotype. The haplotype is encoded with the
* {@code this.markers().allelesToBits()} method.
* @return the second haplotype
*/
public BitArray hap2() {
return new BitArray(this.hap2);
}
/**
* Returns the current estimated phased genotypes. This method converts
* column-major data into row-major data.
* @param estPhase the current estimated phased genotypes for each target
* sample
* @return the current estimated phased genotypes
* @throws NullPointerException if {@code estPhase == null}
*/
public static BitArray[] toBitLists(EstPhase estPhase) {
int nThreads = estPhase.fpd().par().nthreads();
int nMarkers = estPhase.fpd().stage1TargGT().nMarkers();
int nRecsPerBatch = (nMarkers + nThreads - 1)/nThreads;
while (nRecsPerBatch>4096) {
nRecsPerBatch = (nRecsPerBatch+1) >> 1;
}
int stepSize = nRecsPerBatch;
int nSteps = (nMarkers + (stepSize-1)) / stepSize;
return IntStream.range(0, nSteps)
.parallel()
.boxed()
.flatMap(step -> bitLists(estPhase, step, stepSize))
.toArray(BitArray[]::new);
}
private static Stream<BitArray> bitLists(EstPhase estPhase, int step, int stepSize) {
int nSamples = estPhase.fpd().targGT().nSamples();
int nHaps = nSamples<<1;
Markers markers = estPhase.fpd().stage1TargGT().markers();
int mStart = step*stepSize;
int mEnd = Math.min(mStart + stepSize, markers.size());
BitArray[] bitLists = IntStream.range(mStart, mEnd)
.mapToObj(j -> new BitArray(nHaps*markers.marker(j).bitsPerAllele()))
.toArray(BitArray[]::new);
int[] bitsPerAllele = IntStream.range(mStart, mEnd)
.map(m -> markers.marker(m).bitsPerAllele())
.toArray();
for (int s=0; s<nSamples; ++s) {
SamplePhase sampPhase = estPhase.get(s);
int h1 = s<<1;
int h2 = h1 | 0b1;
int inBit1 = markers.sumHapBits(mStart);
int inBit2 = markers.sumHapBits(mStart);
for (int m=mStart; m<mEnd; ++m) {
int mOffset = m - mStart;
int nBits = bitsPerAllele[mOffset];
int startOutBit1 = h1*nBits;
int startOutBit2 = h2*nBits;
for (int i=0; i<nBits; ++i) {
if (sampPhase.hap1.get(inBit1++)) {
bitLists[mOffset].set(startOutBit1 + i);
}
if (sampPhase.hap2.get(inBit2++)) {
bitLists[mOffset].set(startOutBit2 + i);
}
}
}
}
return Arrays.stream(bitLists);
}
}
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