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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 vcf.Steps;
import blbutil.Utilities;
import ints.IntIntMap;
import ints.IntList;
import java.util.PriorityQueue;
import java.util.Random;
import java.util.stream.IntStream;
import beagleutil.CompHapSegment;
import vcf.XRefGT;
/**
* <p>Class {@code LowFreqPhaseStates} has methods for constructing a Li and
* Stephens HMM for a target haplotype. The resulting HMM states are
* enriched for reference haplotypes carrying low frequency variants.
* </p>
* <p>Instances of {@code LowFreqPhaseStates} are not thread-safe.
* </p>
*
* @author Brian L. Browning {@code <browning@uw.edu>}
*/
public final class LowFreqPhaseStates {
private static final int NIL = -103;
private final LowFreqPhaseIbs ibsHaps;
private final PhaseData phaseData;
private final Steps steps;
private final XRefGT allHaps;
private final int nMarkers;
private final int maxStates;
private final int minSteps;
private final IntIntMap hapToLastIbsStep;
private final PriorityQueue<CompHapSegment> q;
private final IntList[] compHapHap;
private final IntList[] compHapEnd;
private final int[] segmentIndex;
private final int[] compHapToHap;
private final int[] compHapToEnd;
/**
* Constructs a new {@code LowFreqPhaseStates} object from the specified
* data.
* @param ibsHaps the IBS haplotype segments
* @param maxStates the maximum number of composite reference
* haplotypes that will be constructed
* @throws IllegalArgumentException if {@code maxStates < 1}
* @throws NullPointerException if {@code ibsHaps == null}
*/
public LowFreqPhaseStates(LowFreqPhaseIbs ibsHaps, int maxStates) {
if (maxStates < 1) {
throw new IllegalArgumentException(String.valueOf(maxStates));
}
this.ibsHaps = ibsHaps;
this.phaseData = ibsHaps.phaseData();
this.steps = phaseData.fpd().stage1Steps();
this.allHaps = ibsHaps.allHaps();
this.nMarkers = allHaps.nMarkers();
this.maxStates = maxStates;
float phaseStep = phaseData.fpd().ibsStep();
this.minSteps = Math.max(200, (int) Math.ceil(1.0f/phaseStep)); // 200 steps and 1 cM
this.hapToLastIbsStep = new IntIntMap(maxStates);
this.q = new PriorityQueue<>(maxStates);
this.compHapHap = IntStream.range(0, maxStates)
.mapToObj(j -> new IntList())
.toArray(IntList[]::new);
this.compHapEnd = IntStream.range(0, maxStates)
.mapToObj(j -> new IntList())
.toArray(IntList[]::new);
this.segmentIndex = new int[maxStates];
this.compHapToHap = new int[maxStates];
this.compHapToEnd = new int[maxStates];
}
/**
* Returns the number of target haplotypes.
* @return the number of target haplotypes
*/
public int nTargHaps() {
return phaseData.fpd().targGT().nHaps();
}
/**
* Returns the number of markers.
* @return the number of markers
*/
public int nMarkers() {
return phaseData.fpd().targGT().nMarkers();
}
/**
* Returns the maximum number of HMM states at a marker.
* @return the maximum number of HMM states at a marker
*/
public int maxStates() {
return maxStates;
}
/**
* Stores the Li and Stephens HMM for the specified target
* haplotype in the specified arrays. The haplotype for the
* {@code j}-th state at the {@code m}-th marker is stored
* in {@code haps[m][j]}. The number of allele mismatches (0 or 1)
* between the haplotype for the {@code j}-th state and the
* target haplotype at the {@code m}-th marker is stored in
* {@code nMismatches[m][j]}.
* The number of HMM states states at each marker is returned.
* @param targHap the haplotype index
* @param haps the two-dimensional array in which the
* haplotype for each HMM state will be stored
* @param nMismatches the two-dimensional array in which the number
* of allele mismatches (0 or 1) for each HMM state will be stored
* @return the number of HMM states at each marker
*
* @throws IndexOutOfBoundsException if
* {@code targHap < 0 || targHap >= this.nTargHaps()}
* @throws IndexOutOfBoundsException if
* {@code haps.length < this.nMarkers()}
* @throws IndexOutOfBoundsException if
* {@code nMismatches.length < this.nMarkers()}
* @throws IndexOutOfBoundsException if {@code haps[m].length}
* is less than the number of HMM states for any marker {@code m}
* satisfying {@code (0 <= m && m < haps.length)}
* @throws IndexOutOfBoundsException if {@code nMismatches[m].length}
* is less than the number of HMM states for any marker {@code m}
* satisfying {@code (0 <= m && m < nMismatches.length)}
* @throws NullPointerException if any array is {@code null}
*/
public int ibsStates(int targHap, int[][] haps, byte[][] nMismatches) {
int nCompHaps = setCompRefHaps(targHap);
copyData(targHap, nCompHaps, haps, nMismatches);
return nCompHaps;
}
private int setCompRefHaps(int targHap) {
q.clear();
hapToLastIbsStep.clear();
for (int j=0, n=maxStates; j<n; ++j) {
compHapHap[j].clear();
compHapEnd[j].clear();
}
for (int step=0, n=steps.size(); step<n; ++step) {
//ibsHaps.ibsHaps(targHap, step, ibsHapList);
addIbsHap(ibsHaps.fwdIbsHap(targHap, step), step);
addIbsHap(ibsHaps.bwdIbsHap(targHap, step), step);
}
if (q.isEmpty()) {
fillQWithRandomHaps(targHap);
}
int nCompHaps = setFinalRefSegs();
return nCompHaps;
}
private void addIbsHap(int ibsHap, int step) {
if (ibsHap<0) {
return;
}
if (hapToLastIbsStep.get(ibsHap, NIL)==NIL) { // hap is not currently in q
updateHeadOfQ();
if (q.size()==maxStates
|| (q.isEmpty()==false && (step - q.peek().lastIbsStep()) >= minSteps)) {
CompHapSegment head = q.poll();
int index = head.compHapIndex();
int prevHap = head.hap();
int nextStart = steps.start((head.lastIbsStep() + step) >>> 1);
hapToLastIbsStep.remove(prevHap);
compHapHap[index].add(ibsHap); // hap of new segment
compHapEnd[index].add(nextStart); // end of old segment
head.updateSegment(ibsHap, nextStart, step);
q.add(head);
}
else {
int index = q.size();
compHapHap[index].add(ibsHap); // hap of new segment
q.add(new CompHapSegment(ibsHap, 0, step, index));
}
}
hapToLastIbsStep.put(ibsHap, step);
}
private void updateHeadOfQ() {
CompHapSegment head = q.peek();
if (head!=null) {
int lastIbsStep = hapToLastIbsStep.get(head.hap(), NIL);
while (head.lastIbsStep()!=lastIbsStep) {
head = q.poll();
head.setLastIbsStep(lastIbsStep);
q.offer(head);
head = q.peek();
lastIbsStep = hapToLastIbsStep.get(head.hap(), NIL);
}
}
}
private int setFinalRefSegs() {
int nCompHaps = q.size();
CompHapSegment head = q.poll();
while (head!=null) {
int compHap = head.compHapIndex();
compHapEnd[compHap].add(nMarkers); // add missing end of last segment
segmentIndex[compHap] = 0;
compHapToHap[compHap] = compHapHap[compHap].get(0);
compHapToEnd[compHap] = compHapEnd[compHap].get(0);
head = q.poll();
}
return nCompHaps;
}
private void copyData(int targHap, int nCompHaps, int[][] haps, byte[][] nMismatches) {
for (int m=0; m<nMarkers; ++m) {
int obsAllele = allHaps.allele(m, targHap);
for (int j=0; j<nCompHaps; ++j) {
if (m==compHapToEnd[j]) {
++segmentIndex[j];
compHapToHap[j] = compHapHap[j].get(segmentIndex[j]);
compHapToEnd[j] = compHapEnd[j].get(segmentIndex[j]);
}
int refHap = compHapToHap[j];
haps[m][j] = refHap;
nMismatches[m][j] = allHaps.allele(m, refHap)==obsAllele
? (byte) 0 : (byte) 1;
}
}
}
private void fillQWithRandomHaps(int hap) {
assert q.isEmpty();
int nHaps = allHaps.nHaps();
int nStates = Math.min(nHaps-2, maxStates);
if (nStates<=0) {
Utilities.exit("ERROR: there is only one sample");
}
else {
Random rand = new Random(phaseData.seed() + hap);
int sample = hap>>1;
int ibsStep = 0;
int startMarker = 0;
for (int j=0; j<nStates; ++j) {
int h = rand.nextInt(nHaps);
while ((h>>1)==sample) {
h = rand.nextInt(nHaps);
}
compHapHap[q.size()].add(h);
q.add(new CompHapSegment(h, startMarker, ibsStep, j));
}
}
}
}
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