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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 ints.IntArray;
import ints.IntList;
import java.util.ArrayList;
import java.util.Arrays;
import java.util.List;
import java.util.stream.Collectors;
import java.util.stream.IntStream;
import java.util.stream.Stream;
import vcf.GT;
/**
* <p>Class {@code Ibs2Sets} partitions markers into steps, and stores
* the sets of samples whose genotypes are consistent with IBS2 in each
* step.</p>
*
* <p>Instances of {@code Ibs2Sets} are immutable.</p>
*
* @author Brian L. Browning {@code <browning@uw.edu>}
*/
public final class Ibs2Sets {
private static final float MAX_MISS_STEP_FREQ = 0.1f;
private final int nTargSamples;
private final int nMarkersM1;
private final IntArray windowStarts;
private final int[][][] ibs2Sets; //[window][targ_sample][ibs2_samples]
/**
* Constructs a new {@code Ibs2Sets} instance from the specified data.
* @param targGT the target genotype data
* @param ibs2Markers the markers and intervals that are used to detect
* IBS2 segments
* @throws IllegalArgumentException if
* {@code targGT.nMarkers() != ibs2Markers.nMarkers()}
* @throws NullPointerException if
* {@code (targGT == null || ibs2Markers == null)}
*/
public Ibs2Sets(GT targGT, Ibs2Markers ibs2Markers) {
if (targGT.nMarkers()!=ibs2Markers.nMarkers()) {
throw new IllegalArgumentException(String.valueOf(ibs2Markers.nMarkers()));
}
this.nMarkersM1 = targGT.nMarkers() - 1;
this.nTargSamples = targGT.nSamples();
this.windowStarts = ibs2Markers.stepStarts();
WrappedIbs2Sets[] results = IntStream.range(0, windowStarts.size())
.parallel()
.mapToObj(w -> ibs2Sets(targGT, ibs2Markers, windowStarts, w))
.toArray(WrappedIbs2Sets[]::new);
this.ibs2Sets = Arrays.stream(results)
.map(wrapper -> wrapper.ibsSets)
.toArray(int[][][]::new);
}
private static WrappedIbs2Sets ibs2Sets(GT targGT, Ibs2Markers ibs2Markers,
IntArray wStarts, int w) {
int wP1 = w + 1;
int start = wStarts.get(w);
int end = (wP1 < wStarts.size()) ? wStarts.get(wP1) : targGT.nMarkers();
int[] stepMarkers = ibs2Markers.markers(start, end);
List<SampClust> partition = new ArrayList<>(1);
partition.add(initCluster(targGT, stepMarkers));
for (int m : stepMarkers) {
int mm = m;
partition = partition.stream()
.flatMap(sampClust -> partition(targGT, sampClust, mm))
.collect(Collectors.toCollection(ArrayList::new));
}
return results(partition, targGT.nSamples());
}
private static SampClust initCluster(GT targGT, int[] stepMarkers) {
// exclude sample with more than MIX_MISS_FREQ missing genotypes
int nTargSamples = targGT.nSamples();
int[] missCnt = new int[nTargSamples];
for (int m : stepMarkers) {
for (int s=0; s<nTargSamples; ++s) {
int hap1 = s <<1;
if (targGT.allele(m, hap1)==-1 || targGT.allele(m, hap1 | 0b1)==-1) {
++missCnt[s];
}
}
}
int maxMiss = (int) Math.floor(MAX_MISS_STEP_FREQ*stepMarkers.length);
int[] initCluster = IntStream.range(0, nTargSamples)
.filter(s -> missCnt[s]<=maxMiss)
.toArray();
boolean isHomozygous = true;
return new SampClust(initCluster, isHomozygous);
}
private static Stream<SampClust> partition(GT targGT, SampClust parent,
int m) {
// this method assumes int[] parent.samples is sorted in increasing order
int nAlleles = targGT.marker(m).nAlleles();
IntList[] gtToList = new IntList[(nAlleles*(nAlleles+1))>>1];
boolean[] isHom = isHom(parent.isHomozygous, nAlleles);
IntList missing = new IntList(32);
for (int s : parent.samples) {
int gtIndex = getGT(m, s, targGT);
if (gtIndex<0) {
missing.add(s);
for (int k=0; k<gtToList.length; ++k) {
if (gtToList[k]!=null) {
gtToList[k].add(s);
}
}
}
else {
if (gtToList[gtIndex]==null) {
gtToList[gtIndex] = new IntList();
for (int j=0, n=missing.size(); j<n; ++j) {
gtToList[gtIndex].add(missing.get(j));
}
}
gtToList[gtIndex].add(s);
}
}
return IntStream.range(0, gtToList.length)
.filter(i -> gtToList[i]!=null && gtToList[i].size()>1)
.mapToObj(i -> new SampClust(gtToList[i].toArray(), isHom[i]));
}
private static int getGT(int m, int s, GT targGT) {
int hap1 = s << 1;
int a1 = targGT.allele(m, hap1);
int a2 = targGT.allele(m, hap1 | 0b1);
if (a1<0 || a2<0) {
return -1;
}
return a1<=a2 ? ((a2*(a2+1))>>1) + a1 : ((a1*(a1+1))>>1) + a2;
}
private static boolean[] isHom(boolean prevIsHom, int nAlleles) {
boolean[] isHom = new boolean[(nAlleles*(nAlleles+1))>>1];
if (prevIsHom) {
for (int a=0; a<nAlleles; ++a) {
isHom[((a*(a+1))>>1) + a] = true;
}
}
return isHom;
}
private static WrappedIbs2Sets results(List<SampClust> ibd2Lists,
int nTargSamples) {
final int[] EMPTY_ARRAY = new int[0];
int[][] results = IntStream.range(0, nTargSamples)
.mapToObj(i -> EMPTY_ARRAY)
.toArray(int[][]::new);
for (int j=0, n=ibd2Lists.size(); j<n; ++j) {
SampClust ibd2List = ibd2Lists.get(j);
if (ibd2List.isHomozygous==false) {
int[] ia = ibd2List.samples;
assert ia.length>1;
for (int s : ia) {
if (results[s]==EMPTY_ARRAY) {
results[s] = ia;
}
else {
// sample can be in >1 list due to missing genotypes
IntStream is1 = Arrays.stream(results[s]);
IntStream is2 = Arrays.stream(ia);
results[s] = IntStream.concat(is1, is2)
.sorted()
.distinct()
.toArray();
}
}
}
}
return new WrappedIbs2Sets(results);
}
/**
* Returns the number of target samples.
* @return the number of target samples
*/
public int nTargSamples() {
return nTargSamples;
}
/**
* Returns the detected IBS2 sample segments.
* @param sample a sample index
* @return the detected IBS2 sample segments
* @throws IndexOutOfBoundsException if
* {@code sample < 0 || sample >= this.nTargSamples()}
*/
public SampleSeg[] segList(int sample) {
List<SampleSeg> list = new ArrayList<>();
for (int w=0; w<ibs2Sets.length; ++w) {
int[] ia = ibs2Sets[w][sample];
if (ia.length>0) {
int wP1 = w + 1;
int start = windowStarts.get(w);
int inclEnd = wP1 < windowStarts.size()
? windowStarts.get(wP1) - 1 : nMarkersM1;
for (int s2 : ia) {
if (s2!=sample) {
list.add(new SampleSeg(s2, start, inclEnd));
}
}
}
}
return list.toArray(new SampleSeg[0]);
}
private static class SampClust {
private final int[] samples;
private final boolean isHomozygous;
private SampClust(int[] samples, boolean areHomozygous) {
this.samples = samples;
this.isHomozygous = areHomozygous;
}
private SampClust(int nSamples) {
this.samples = IntStream.range(0, nSamples).toArray();
this.isHomozygous = true;
}
}
private static class WrappedIbs2Sets {
// final field ensures visibility of IBS sets across threads
private final int[][] ibsSets; // [targ_sample][ibs2_samples]
private WrappedIbs2Sets(int[][] ibsSets) {
this.ibsSets = ibsSets;
}
}
}
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