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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 beagleutil.PbwtDivUpdater;
import ints.IndexArray;
import ints.WrappedIntArray;
import java.util.Arrays;
import java.util.Random;
import java.util.stream.IntStream;
import vcf.XRefGT;
/**
* <p>Class {@code PbwtPhaseIBS} uses the Positional Burrows-Wheeler
* Transform (PBWT) to find long IBS haplotypes for each sample that
* contain a specified small genomic interval.</p>
*
* <p>Instances of class {@code PbwtPhaseIbs} are thread-safe.</p>
*
* <p>Reference: Durbin, R. 2014. Bioinformatics 30(9):1266–1272.
* doi:10.1093/bioinformatics/btu014</p>
*
* @author Brian L. Browning {@code <browning@uw.edu>}
*/
public final class PbwtPhaseIbs {
private final PhaseData phaseData;
private final XRefGT allHaps;
private final WrappedIntArray[] ibsHaps; //[step][targ hap]
/**
* Constructs a new {@code PbwtPhaseIBS} instance from the
* specified data.
* @param phaseData the current genotype phase estimates and parameter
* values
* @param codedSteps the coded steps
* @param useBwd {@code true} if last-to-first PBWT should be used
* @throws IllegalArgumentException if
* {@code phaseData.fpd().stage1Steps() != codedSteps.steps()}
* @throws IllegalArgumentException if
* {@code phaseData.fpd().stage1XRefGT()!=codedSteps.refHaps()}
* @throws IllegalArgumentException if
* {@code phaseData.fpd().targGT().samples()!=codedSteps.targSamples()}
* @throws NullPointerException if
* {@code phaseData == null || codedSteps == null}
*/
public PbwtPhaseIbs(PhaseData phaseData, CodedSteps codedSteps,
boolean useBwd) {
checkConsistency(phaseData, codedSteps);
this.phaseData = phaseData;
this.allHaps = codedSteps.allHaps();
PbwtIbsData data = new PbwtIbsData(phaseData, codedSteps);
if (useBwd) {
this.ibsHaps = IntStream.range(0, data.nBatches())
.parallel()
.mapToObj(j -> bwdIbsHaps(data, j))
.flatMap(a -> Arrays.stream(a))
.toArray(WrappedIntArray[]::new);
}
else {
this.ibsHaps = IntStream.range(0, data.nBatches())
.parallel()
.mapToObj(j -> fwdIbsHaps(data, j))
.flatMap(a -> Arrays.stream(a))
.toArray(WrappedIntArray[]::new);
}
}
private static void checkConsistency(PhaseData phaseData,
CodedSteps codedSteps) {
FixedPhaseData fpd = phaseData.fpd();
if (fpd.stage1Steps()!=codedSteps.steps()
|| fpd.stage1XRefGT()!=codedSteps.refHaps()
|| fpd.targGT().samples()!=codedSteps.targSamples()) {
throw new IllegalArgumentException("inconsistent data");
}
}
private WrappedIntArray[] bwdIbsHaps(PbwtIbsData data, int batch) {
int startStep = data.startStep(batch);
int endStep = data.endStep(batch);
int bufferEndStep = data.bufferEndStep(endStep);
WrappedIntArray[] ibsHaps0 = new WrappedIntArray[endStep - startStep];
int nHaps = data.nHaps();
PbwtDivUpdater pbwt = new PbwtDivUpdater(nHaps);
int[] a = IntStream.range(0, nHaps).toArray();
int[] d = IntStream.range(0, nHaps+1).map(j -> (bufferEndStep-1)).toArray(); // last entry is sentinal
for (int j=(bufferEndStep-1); j>=endStep; --j) {
IndexArray ia = data.codedSteps().get(j);
pbwt.bwdUpdate(ia, ia.valueSize(), j, a, d);
}
for (int j=(endStep-1); j>=startStep; --j) {
IndexArray ia = data.codedSteps().get(j);
pbwt.bwdUpdate(ia, ia.valueSize(), j, a, d);
ibsHaps0[j-startStep] = getBwdIbsHaps(j, a, d, data);
}
return ibsHaps0;
}
private WrappedIntArray[] fwdIbsHaps(PbwtIbsData data, int batch) {
int startStep = data.startStep(batch);
int endStep = data.endStep(batch);
int bufferStartStep = data.bufferStartStep(startStep);
WrappedIntArray[] ibsHaps0 = new WrappedIntArray[endStep - startStep];
int nHaps = data.nHaps();
PbwtDivUpdater pbwt = new PbwtDivUpdater(nHaps);
int[] a = IntStream.range(0, nHaps).toArray();
int[] d = IntStream.range(0, nHaps+1).map(j -> bufferStartStep).toArray(); // last entry is sentinal
for (int j=bufferStartStep; j<startStep; ++j) {
IndexArray ia = data.codedSteps().get(j);
pbwt.fwdUpdate(ia, ia.valueSize(), j, a, d);
}
for (int j=startStep; j<endStep; ++j) {
IndexArray ia = data.codedSteps().get(j);
pbwt.fwdUpdate(ia, ia.valueSize(), j, a, d);
ibsHaps0[j-startStep] = getfwdIbsHaps(j, a, d, data);
}
return ibsHaps0;
}
private WrappedIntArray getBwdIbsHaps(int step, int[] a, int[] d, PbwtIbsData data) {
Random rand = new Random(phaseData.seed() + step);
int mStart = data.codedSteps().steps().start(step);
int mInclEnd = data.codedSteps().steps().end(step) - 1;
int[] selectedHaps = new int[data.nTargHaps()];
Ibs2 ibs2 = phaseData.fpd().stage1Ibs2();
d[0] = d[a.length] = step - 2; // set sentinals
// no need to save and restore old d[0], d[a.length] values
for (int i=0; i<a.length; ++i) {
if (a[i]<data.nTargHaps()) {
int hap = a[i];
int s1 = hap>>1;
int u = i; // inclusive start
int v = i + 1; // exclusive end
int uNextMatchEnd = d[u];
int vNextMatchEnd = d[v];
while ((v - u)<data.nCandidates()
&& (step<=uNextMatchEnd || step<=vNextMatchEnd)) {
if (uNextMatchEnd<=vNextMatchEnd) {
vNextMatchEnd = Math.min(d[++v], vNextMatchEnd);
}
else {
uNextMatchEnd = Math.min(d[--u], uNextMatchEnd);
}
}
int n = v-u;
selectedHaps[hap] = -1;
if (n>1) {
int index = u + rand.nextInt(n);
for (int j=0; j<n; ++j, ++index) {
if (index==v) {
index = u;
}
if (index!=i) {
if (ibs2.areIbs2(s1, a[index]>>1, mStart, mInclEnd)==false) {
selectedHaps[hap] = a[index];
break;
}
}
}
}
}
}
return new WrappedIntArray(selectedHaps);
}
private WrappedIntArray getfwdIbsHaps(int step, int[] a, int[] d,
PbwtIbsData data) {
Steps steps = phaseData.fpd().stage1Steps();
Random rand = new Random(phaseData.seed() + step);
int nTargHaps = phaseData.fpd().targGT().nHaps();
int mStart = steps.start(step);
int mInclEnd = steps.end(step) - 1;
int[] selectedHaps = new int[nTargHaps];
Ibs2 ibs2 = phaseData.fpd().stage1Ibs2();
d[0] = d[a.length] = step + 2; // set sentinals
// no need to save and restore old d[0], d[a.length] values
for (int i=0; i<a.length; ++i) {
if (a[i]<nTargHaps) {
int hap = a[i];
int s1 = hap>>1;
int u = i; // inclusive start
int v = i + 1; // exclusive end
int uNextMatchStart = d[u];
int vNextMatchStart = d[v];
while ((v - u)<data.nCandidates()
&& (uNextMatchStart<=step || vNextMatchStart<=step)) {
if (vNextMatchStart<=uNextMatchStart) {
vNextMatchStart = Math.max(d[++v], vNextMatchStart);
}
else {
uNextMatchStart = Math.max(d[--u], uNextMatchStart);
}
}
int n = v-u;
selectedHaps[hap] = -1;
if (n>1) {
int index = u + rand.nextInt(n);
for (int j=0; j<n; ++j, ++index) {
if (index==v) {
index = u;
}
if (index!=i) {
if (ibs2.areIbs2(s1, a[index]>>1, mStart, mInclEnd)==false) {
selectedHaps[hap] = a[index];
break;
}
}
}
}
}
}
return new WrappedIntArray(selectedHaps);
}
/**
* Returns the current genotype phase estimates and parameter values.
* @return the current genotype phase estimates and parameter values
*/
public PhaseData phaseData() {
return phaseData;
}
/**
* Returns the estimated phased genotypes for the target and reference
* samples.
* @return the estimated phased genotypes for the target and reference
* samples
*/
public XRefGT allHaps() {
return allHaps;
}
/**
* Returns the index of a haplotype that is identical by state
* with the specified target haplotype in the specified genomic interval,
* or {@code -1} if there is no identical-by-state haplotype.
* @param hap a target haplotype index
* @param step an index of a genomic interval
* @return the index of a haplotype that is identical by state
* with the specified haplotype int the specified genomic interval
* @throws IndexOutOfBoundsException if
* {@code hap < 0 || hap >= this.phaseData().targGT().nHaps()}
* @throws IndexOutOfBoundsException if
* {@code step < 0 || step >= this.phaseData().fpd().stage1Steps().size()}
*/
public int ibsHap(int hap, int step) {
return ibsHaps[step].get(hap);
}
}
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