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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 imp;
import blbutil.Const;
import java.io.PrintWriter;
import java.text.DecimalFormat;
import java.util.stream.IntStream;
import vcf.Marker;
/**
* <p>Class {@code ImputeRecBuilder} contains methods for constructing
* and printing a VCF record in VCF 4.3 format. The sample data in
* the output VCF record are in the same order that the data were added
* with the {@code addSampleData()} method.
* </p>
* <p>Instances of class {@code ImputeRecBuilder} are not thread-safe.
* </p>
*
* @author Brian L. Browning {@code <browning@uw.edu>}
*/
public final class ImputedRecBuilder {
private static final DecimalFormat DF = new DecimalFormat("#.##");
private static final DecimalFormat DF2 = new DecimalFormat("0.00");
private static final DecimalFormat DF4 = new DecimalFormat("0.0000");
private static final String[] DS_VALS = IntStream.range(0, 201)
.mapToObj(j -> DF.format(j/100.0))
.toArray(String[]::new);
private static final String[] R2_VALS = IntStream.range(0, 101)
.limit(101)
.mapToObj(i -> (DS_VALS[i].length()!=4 ? DF2.format(i/100.0) : DS_VALS[i]))
.toArray(String[]::new);
private static final String[] DEFAULT_HOM_REF_FIELDS = defaultHomRefFields();
private final Marker marker;
private final int nAlleles;
private final int nInputTargHaps;
private final boolean ap;
private final boolean gp;
private final float[] sumAlProbs;
private final float[] sumAlProbs2;
private final String[] homRefField;
private final StringBuilder sampleData;
private int hapCnt;
/**
* Constructs a new {@code ImputedRecBuilder} instance for the specified
* number of samples.
*
* @param marker the marker corresponding to the VCF record
* @param nInputTargHaps the number of input target haplotypes for haploid
* and diploid samples
* @param ap {@code true} if posterior allele probabilities are to be printed
* @param gp {@code true} if posterior genotype probabilities are to be printed
* @throws IllegalArgumentException if {@code nInputTargHaps < 1}
* @throws NullPointerException if {@code marker == null}
*/
public ImputedRecBuilder(Marker marker, int nInputTargHaps, boolean ap,
boolean gp) {
if (nInputTargHaps < 1) {
throw new IllegalArgumentException(String.valueOf(nInputTargHaps));
}
this.marker = marker;
this.nAlleles = marker.nAlleles();
this.nInputTargHaps = nInputTargHaps;
this.ap = ap;
this.gp = gp;
this.sumAlProbs = new float[nAlleles];
this.sumAlProbs2 = new float[nAlleles];
this.sampleData = new StringBuilder(200 + nInputTargHaps*5);
this.homRefField = (ap || gp) ? homRefFields(ap, gp)
: DEFAULT_HOM_REF_FIELDS;
this.hapCnt = 0;
}
/**
* Returns the marker in the VCF record.
* @return the marker in the VCF record
*/
public Marker marker() {
return marker;
}
/**
* Returns the number of input target haplotypes for haploid
* and diploid samples.
* @return the number of input target haplotypes for haploid
* and diploid samples
*/
public int nInputTargHaps() {
return nInputTargHaps;
}
/**
* Returns the number of imputed alleles added by the addSampleData()
* methods.
* @return the number of imputed alleles added by the addSampleData()
* methods
*/
public int hapCnt() {
return hapCnt;
}
/**
* Scales the specified probabilities for each allele to each sum to 1.0,
* and adds the sample data to the VCF record. The contract
* for this method is undefined if any element of the specified arrays is
* not a finite non-negative number.
* @param a1 the allele probabilities for the first allele
* @param a2 the allele probabilities for the second allele
* @throws IndexOutOfBoundsException if
* {@code a1.length < this.marker().nAlleles()}
* @throws IndexOutOfBoundsException if
* {@code a2.length < this.marker().nAlleles()}
* @throws NullPointerException if {@code a1 == null || a2 == null}
*/
public void addSampleData(float[] a1, float[] a2) {
hapCnt+=2;
if (a1[0]==1.0f && a2[0]==1.0f && a1.length < DEFAULT_HOM_REF_FIELDS.length) {
sampleData.append(homRefField[a1.length]);
}
else {
scale(a1);
scale(a2);
sampleData.append(Const.tab);
sampleData.append(maxIndex(a1));
sampleData.append(Const.phasedSep);
sampleData.append(maxIndex(a2));
for (int a=1; a<nAlleles; ++a) {
float dose = a1[a] + a2[a];
float dose2 = a1[a]*a1[a] + a2[a]*a2[a];
sumAlProbs[a] += dose;
sumAlProbs2[a] += dose2;
sampleData.append( (a==1) ? Const.colon : Const.comma );
sampleData.append(DS_VALS[(int) Math.rint(100*dose)]);
}
if (ap) {
for (int a=1; a<nAlleles; ++a) {
sampleData.append( (a==1) ? Const.colon : Const.comma );
sampleData.append(DS_VALS[(int) Math.rint(100*a1[a])]);
}
for (int a=1; a<nAlleles; ++a) {
sampleData.append( (a==1) ? Const.colon : Const.comma );
sampleData.append(DS_VALS[(int) Math.rint(100*a2[a])]);
}
}
if (gp) {
for (int i2=0; i2<nAlleles; ++i2) {
for (int i1=0; i1<=i2; ++i1) {
float prob = a1[i1]*a2[i2];
if (i1!=i2) {
prob += a1[i2]*a2[i1];
}
sampleData.append( (i2==0) ? Const.colon : Const.comma );
sampleData.append(DS_VALS[(int) Math.rint(100*prob)]);
}
}
}
}
}
/**
* Scales the specified probabilities for each allele to each sum to 1.0,
* and adds the sample data to the VCF record. The contract
* for this method is undefined if any element of the specified arrays is
* not a finite non-negative number.
* @param a1 the allele probabilities
* @throws IndexOutOfBoundsException if
* {@code a1.length < this.marker().nAlleles()}
* @throws IndexOutOfBoundsException if
* {@code a2.length < this.marker().nAlleles()}
* @throws NullPointerException if {@code a1 == null || a2 == null}
*/
public void addSampleData(float[] a1) {
++hapCnt;
scale(a1);
sampleData.append(Const.tab);
sampleData.append(maxIndex(a1));
for (int a=1; a<nAlleles; ++a) {
float dose = a1[a];
float dose2 = a1[a]*a1[a];
sumAlProbs[a] += dose;
sumAlProbs2[a] += dose2;
sampleData.append( (a==1) ? Const.colon : Const.comma );
sampleData.append(DS_VALS[(int) Math.rint(100*dose)]);
}
if (ap) {
for (int a=1; a<nAlleles; ++a) {
sampleData.append( (a==1) ? Const.colon : Const.comma );
sampleData.append(DS_VALS[(int) Math.rint(100*a1[a])]);
}
}
}
private static void scale(float[] fa) {
float sum = 0f;
for (float f : fa) {
sum += f;
}
for (int j=0; j<fa.length; ++j) {
fa[j] /= sum;
}
}
private static int maxIndex(float[] fa) {
int maxIndex=0;
for (int j=1; j<fa.length; ++j) {
if (fa[j] > fa[maxIndex]) {
maxIndex = j;
}
}
return maxIndex;
}
/**
* Prints the VCF record to the specified {@code PrintWriter}.
* The INFO field of the VCF record will include the DR2 (dose r2) and
* AF (ALT allele frequency) subfields.
* @param isImputed {@code true} if the INFO field of the VCF record will
* have an IMP flag and {@code false} otherwise
*@param out the {@code PrintWriter} to which the VCF record will be
* printed
* @throws IllegalStateException if
* {@code this.hapCnt() != this.nInputTargHaps()}
* @throws NullPointerException if {@code out == null}
*/
public void printRec(PrintWriter out, boolean isImputed) {
if (hapCnt != nInputTargHaps) {
throw new IllegalStateException("inconsistent data");
}
printMarkerFields(marker, out);
out.print(Const.tab);
out.print(Const.MISSING_DATA_CHAR); // QUAL
out.print(Const.tab);
out.print("PASS"); // FILTER
out.print(Const.tab);
printInfoField(out, isImputed); // INFO
out.print(Const.tab);
out.print("GT:DS"); // FORMAT
if (ap) {
out.print(":AP1:AP2");
}
if (gp) {
out.print(":GP");
}
out.println(sampleData);
}
private static void printMarkerFields(Marker marker, PrintWriter out) {
out.print(marker.chrom());
out.print(Const.tab);
out.print(marker.pos());
int nIds = marker.nIds();
if (nIds==0) {
out.print(Const.tab);
out.print(Const.MISSING_DATA_CHAR);
}
else {
for (int j=0; j<nIds; ++j) {
out.print(j==0 ? Const.tab : Const.semicolon);
out.print(marker.id(j));
}
}
int nAlleles = marker.nAlleles();
if (nAlleles==1) {
out.print(Const.tab);
out.print(marker.allele(0));
out.print(Const.tab);
out.print(Const.MISSING_DATA_CHAR);
}
else {
for (int j=0; j<nAlleles; ++j) {
out.print(j<2 ? Const.tab : Const.comma);
out.print(marker.allele(j));
}
}
}
private void printInfoField(PrintWriter out, boolean isImputed) {
if (nAlleles==1) {
if (isImputed) {
out.print("IMP");
}
}
else {
for (int a=1; a<nAlleles; ++a) {
out.print( (a==1) ? "DR2=" : Const.comma);
out.print(R2_VALS[(int) Math.rint(100*r2(a))]);
}
for (int a=1; a<nAlleles; ++a) {
out.print( (a==1) ? ";AF=" : Const.comma);
out.print(DF4.format(sumAlProbs[a]/nInputTargHaps));
}
if (marker.end()!=-1) {
out.print(";END=");
out.print(marker.end());
}
if (isImputed) {
out.print(";IMP");
}
}
}
private float r2(int allele) {
float sum = sumAlProbs[allele];
if (sum==0f) {
return 0f;
}
else {
float sum2 = sumAlProbs2[allele];
float meanTerm = sum*sum/(nInputTargHaps);
float num = (sum2 - meanTerm);
float den = (sum - meanTerm);
return num <= 0 ? 0f : num/den;
}
}
private static String[] defaultHomRefFields() {
String[] sa = new String[5];
sa[1] = Const.tab + "0|0";
sa[2] = Const.tab + "0|0:0";
for (int j=3; j<sa.length; ++j) {
sa[j] = sa[j-1] + ",0";
}
return sa;
}
private static String[] homRefFields(boolean ap, boolean gp) {
String[] homRefField = new String[DEFAULT_HOM_REF_FIELDS.length];
for (int nAl=1; nAl<homRefField.length; ++nAl) {
StringBuilder sb = new StringBuilder(DEFAULT_HOM_REF_FIELDS[nAl]);
if (ap) {
for (int a=1; a<nAl; ++a) {
sb.append( (a==1) ? Const.colon : Const.comma );
sb.append(DS_VALS[0]);
}
for (int a=1; a<nAl; ++a) {
sb.append( (a==1) ? Const.colon : Const.comma );
sb.append(DS_VALS[0]);
}
}
if (gp) {
sb.append(Const.colon);
sb.append(DS_VALS[100]);
for (int i2=1; i2<nAl; ++i2) {
for (int i1=0; i1<=i2; ++i1) {
sb.append(Const.comma);
sb.append(DS_VALS[0]);
}
}
}
homRefField[nAl] = sb.toString();
}
return homRefField;
}
}
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