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fix(qannotate): MIUN was not being applied appropriately to SNPs #387

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Merged
merged 1 commit into from
Feb 11, 2025
Merged

fix(qannotate): MIUN was not being applied appropriately to SNPs #387

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61 changes: 34 additions & 27 deletions qannotate/src/au/edu/qimr/qannotate/modes/ConfidenceMode.java
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Original file line number Diff line number Diff line change
Expand Up @@ -8,13 +8,11 @@

import java.io.File;
import java.io.IOException;
import java.util.ArrayList;
import java.util.Arrays;
import java.util.Collections;
import java.util.List;
import java.util.Map;
import java.util.concurrent.atomic.AtomicInteger;
import java.util.stream.Collectors;

import org.qcmg.common.log.QLogger;
import org.qcmg.common.log.QLoggerFactory;
Expand Down Expand Up @@ -55,6 +53,8 @@ public class ConfidenceMode extends AbstractMode {
public static final int sBiasAltPercentage = 5;
public static final int sBiasCovPercentage = 5;

private static final int[] ZERO_ARRAY = {0, 0};

@Deprecated // using values (both hard cutoff and percentage) from MIN for MIUN annotation
public static final int MIUN_CUTOFF = 2; // based on existing values

Expand Down Expand Up @@ -230,7 +230,7 @@ void addAnnotation() {
/*
* look for MIUN, but only if we don't already have MIN
*/
checkMIUN(failedFilterStringBuilder, ffArr, i, alts, cov);
checkMIUN(failedFilterStringBuilder, ffArr, i, alts, cov, alleleDist);

if (!failedFilterStringBuilder.toString().contains(VcfHeaderUtils.FILTER_COVERAGE) && cov < controlCovCutoffForSomaticCalls) {
StringUtils.updateStringBuilder(failedFilterStringBuilder, VcfHeaderUtils.FILTER_COVERAGE, Constants.SEMI_COLON);
Expand All @@ -243,7 +243,7 @@ void addAnnotation() {
String gt = gtArray[i];
if ( ! StringUtils.isNullOrEmptyOrMissingData(gt) && ! "0/0".equals(gt)) {
int index = gt.indexOf(Constants.SLASH);
int[] gts = new int[]{Integer.parseInt(gt.substring(0, index)), Integer.parseInt(gt.substring(index + 1))};
int[] gts = new int[]{Integer.parseInt(gt, 0, index, 10), Integer.parseInt(gt, index + 1, gt.length(), 10)};

if (!alleleDist.isEmpty() && !isGATKCall) {
checkStrandBias(alts, failedFilterStringBuilder, alleleDist, gts, sBiasCovPercentage, sBiasAltPercentage);
Expand Down Expand Up @@ -304,12 +304,12 @@ void addAnnotation() {
}
}

private void checkMIUN(StringBuilder fSb, String[] ffArr, int i, String[] alts, int cov) {
private void checkMIUN(StringBuilder fSb, String[] ffArr, int i, String[] alts, int cov, Map<String, int[]> alleleDist) {
if (!fSb.toString().contains(VcfHeaderUtils.FILTER_MUTATION_IN_NORMAL)) {
if (null != ffArr && ffArr.length > i) {
String failedFilter = ffArr[i];
// using the same values as for the MIN annotation
checkMIUN(alts, cov, failedFilter, fSb, minCutoff, (float) minPercentage);
checkMIUN(alts, cov, failedFilter, fSb, minCutoff, (float) minPercentage, alleleDist);
}
}
}
Expand Down Expand Up @@ -385,7 +385,7 @@ public static void checkNNS(String nnsString, StringBuilder sb, int nnsCount) {
public static void checkMIN(String[] alts, int coverage, Map<String, int[]> alleleDist, StringBuilder sb, int minCutoff, float minPercentage) {
if (null != alts && null != alleleDist) {
for (String alt : alts) {
int altCov = Arrays.stream(alleleDist.getOrDefault(alt, new int[]{0, 0})).sum();
int altCov = Arrays.stream(alleleDist.getOrDefault(alt, ZERO_ARRAY)).sum();
boolean min = VcfUtils.mutationInNormal(altCov, coverage, minPercentage, minCutoff);
if (min) {
StringUtils.updateStringBuilder(sb, VcfHeaderUtils.FILTER_MUTATION_IN_NORMAL, Constants.SEMI_COLON);
Expand All @@ -407,25 +407,31 @@ public static void checkMIN(String[] alts, int coverage, Map<String, int[]> alle
* @param miunCutoff The minimum coverage cutoff for MIUN
* @param miunPercentage The minimum percentage cutoff for MIUN
*/
public static void checkMIUN(String[] alts, int coverage, String failedFilter, StringBuilder sb, int miunCutoff, float miunPercentage) {
if (null != alts && !StringUtils.isNullOrEmptyOrMissingData(failedFilter)) {
public static void checkMIUN(String[] alts, int coverage, String failedFilter, StringBuilder sb, int miunCutoff, float miunPercentage, Map<String, int[]> alleleDist) {
if (alts == null || alts.length == 0 || StringUtils.isNullOrEmptyOrMissingData(failedFilter)) {
return;
}

int totalCoverage = coverage + getCoverageFromFailedFilterString(failedFilter);
float cutoffToUse = Math.max(miunCutoff, (miunPercentage / 100) * totalCoverage);
int totalCoverage = coverage + getCoverageFromFailedFilterString(failedFilter);
float cutoffToUse = Math.max(miunCutoff, (miunPercentage / 100) * totalCoverage);

for (String alt : alts) {
int altIndex = failedFilter.indexOf(alt);
if (altIndex > -1) {
/*
* bases are separated by colons
*/
int semiColonIndex = failedFilter.indexOf(Constants.SEMI_COLON, altIndex);
int failedFilterCount = Integer.parseInt(failedFilter, altIndex + alt.length(), semiColonIndex > -1 ? semiColonIndex : failedFilter.length(), 10);

for (String alt : alts) {
int altIndex = failedFilter.indexOf(alt);
if (altIndex > -1) {
/*
* bases are separated by colons
*/
int semiColonIndex = failedFilter.indexOf(Constants.SEMI_COLON, altIndex);
int failedFilterCount = Integer.parseInt(failedFilter.substring(altIndex + alt.length(), semiColonIndex > -1 ? semiColonIndex : failedFilter.length()));
if (failedFilterCount >= cutoffToUse) {
StringUtils.updateStringBuilder(sb, VcfHeaderUtils.FILTER_MUTATION_IN_UNFILTERED_NORMAL, Constants.SEMI_COLON);
break;
}
// Add coverage from alleleDist map
int[] passedFilterCoverage = null != alleleDist ? alleleDist.getOrDefault(alt, ZERO_ARRAY) : ZERO_ARRAY;
int passedFilterCoverageSum = passedFilterCoverage[0] + passedFilterCoverage[1];
failedFilterCount += passedFilterCoverageSum;

if (failedFilterCount >= cutoffToUse) {
StringUtils.updateStringBuilder(sb, VcfHeaderUtils.FILTER_MUTATION_IN_UNFILTERED_NORMAL, Constants.SEMI_COLON);
break;
}
}
}
Expand All @@ -451,8 +457,8 @@ public static int endsOfReads(String[] alts, String gt, Map<String, int[]> oabsM
Map<String, int[]> eorMap = VcfUtils.getAllelicCoverageWithStrand(eor);
for (String alt : alts) {
if (gt.contains("" + i)) {
int[] altCov = oabsMap.getOrDefault(alt, new int[]{0, 0});
int[] altCovEOR = eorMap.getOrDefault(alt, new int[]{0, 0});
int[] altCov = oabsMap.getOrDefault(alt, ZERO_ARRAY);
int[] altCovEOR = eorMap.getOrDefault(alt, ZERO_ARRAY);
int middleOfReadForwardStrand = altCov[0] - altCovEOR[0];
int middleOfReadReverseStrand = altCov[1] - altCovEOR[1];
int middleOfReadCount = middleOfReadForwardStrand + middleOfReadReverseStrand;
Expand Down Expand Up @@ -545,7 +551,8 @@ public static int[] getFieldOfInts(String value) {
}
int cI = value.indexOf(Constants.COMMA);
if (cI == -1) return new int[]{Integer.parseInt(value)};
return new int[]{Integer.parseInt(value.substring(0, cI)), Integer.parseInt(value.substring(cI + 1))};
return new int[]{Integer.parseInt(value, 0, cI, 10), Integer.parseInt(value, cI + 1, value.length(), 10)};
// return new int[]{Integer.parseInt(value.substring(0, cI)), Integer.parseInt(value.substring(cI + 1))};
}

/**
Expand All @@ -566,7 +573,7 @@ public static int getCoverageFromFailedFilterString(String ff) {
// could probably start this at 1....
for (int i = 0; i < ff.length(); ) {
if (Character.isDigit(ff.charAt(i))) {
cov += Integer.parseInt(ff.substring(i, semiColonIndex > -1 ? semiColonIndex : ff.length()));
cov += Integer.parseInt(ff, i, semiColonIndex > -1 ? semiColonIndex : ff.length(), 10);
if (semiColonIndex == -1) {
break;
} else {
Expand Down
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