package picard.vcf;
import htsjdk.samtools.metrics.MetricsFile;
import htsjdk.samtools.util.FormatUtil;
import htsjdk.samtools.util.IOUtil;
import htsjdk.variant.variantcontext.Allele;
import htsjdk.variant.variantcontext.Genotype;
import htsjdk.variant.variantcontext.GenotypeBuilder;
import htsjdk.variant.variantcontext.VariantContext;
import htsjdk.variant.variantcontext.VariantContextBuilder;
import org.testng.Assert;
import org.testng.annotations.AfterClass;
import org.testng.annotations.DataProvider;
import org.testng.annotations.Test;
import picard.vcf.GenotypeConcordanceStates.CallState;
import picard.vcf.GenotypeConcordanceStates.TruthAndCallStates;
import picard.vcf.GenotypeConcordanceStates.TruthState;
import java.io.File;
import java.io.FileNotFoundException;
import java.io.FileReader;
import java.util.ArrayList;
import java.util.Arrays;
import java.util.Collections;
import java.util.HashMap;
import java.util.HashSet;
import java.util.List;
import java.util.Map;
import java.util.Set;
public class GenotypeConcordanceTest {
private static final File OUTPUT_DATA_PATH = IOUtil.createTempDir("GenotypeConcordanceTest", null);
private static final File TEST_DATA_PATH = new File("testdata/picard/vcf/");
// Test VCFs
private static final File CEU_TRIOS_SNPS_VCF = new File(TEST_DATA_PATH, "CEUTrio-snps.vcf");
private static final File CEU_TRIOS_INDELS_VCF = new File(TEST_DATA_PATH, "CEUTrio-indels.vcf");
// Test that we notice a difference on the first line
private static final File CEU_TRIOS_SNPS_FIRST_LINE_DIFF_VCF = new File(TEST_DATA_PATH, "CEUTrio-snps_first_line_diff.vcf");
// Test that we notice a difference on the last line
private static final File CEU_TRIOS_SNPS_LAST_LINE_DIFF_VCF = new File(TEST_DATA_PATH, "CEUTrio-snps_last_line_diff.vcf");
// Test that we notice a deleted line
private static final File CEU_TRIOS_SNPS_DEL_LINE_VCF = new File(TEST_DATA_PATH, "CEUTrio-snps_del_line.vcf");
// Existing/expected base metrics file names
private static final String CEU_TRIOS_SNPS_VS_CEU_TRIOS_SNPS_GC = "CEUTrio-snps_vs_CEUTrio-snps_GtConcordanceDiff";
private static final String CEU_TRIOS_INDELS_VS_CEU_TRIOS_INDELS_GC = "CEUTrio-indels_vs_CEUTrio-indels_GtConcordanceDiff";
private static final String CEU_TRIOS_SNPS_VS_CEU_TRIOS_SNPS_FIRST_LINE_DIFF_GC = "CEUTrio-snps_CEUTrio-snps_first_line_GtConcordanceDiff";
private static final String CEU_TRIOS_SNPS_VS_CEU_TRIOS_SNPS_LAST_LINE_DIFF_GC = "CEUTrio-snps_CEUTrio-snps_last_line_GtConcordanceDiff";
private static final String CEU_TRIOS_SNPS_VS_CEU_TRIOS_SNPS_DEL_LINE_GC = "CEUTrio-snps_CEUTrio-snps_del_line_GtConcordanceDiff";
private static final String CEU_TRIOS_SNPS_VS_CEU_TRIOS_SNPS_GC_ALL_ROWS = "CEUTrio-snps_vs_CEUTrio-snps_GtConcordanceDiff_AllRows";
private static final String CEU_TRIOS_SNPS_VS_CEU_TRIOS_SNPS_GC_MIN_GQ = "CEUTrio-snps_vs_CEUTrio-snps_GtConcordanceDiff_MinGq";
private static final String CEU_TRIOS_SNPS_VS_CEU_TRIOS_SNPS_GC_MIN_DP = "CEUTrio-snps_vs_CEUTrio-snps_GtConcordanceDiff_MinDp";
private static final File INTERVALS_FILE = new File(TEST_DATA_PATH, "IntervalListChr1Small.interval_list");
private static final String TRUTH_SAMPLE_NAME = "Foo";
private static final String CALL_SAMPLE_NAME = "Foo";
// A [ref] / T at 10
private static final String snpLoc = "chr1";
private static final int snpLocStart = 10;
private static final int snpLocStop = 10;
private static final Allele Aref = Allele.create("A", true);
private static final Allele C = Allele.create("C");
private static final Allele G = Allele.create("G");
private static final Allele T = Allele.create("T");
private static final Allele AA = Allele.create("AA");
private static final Allele AAA = Allele.create("AAA");
private static final Allele AAAA = Allele.create("AAAA");
private static final Allele AAAAA = Allele.create("AAAAA");
@AfterClass
public void teardown() {
IOUtil.deleteDirectoryTree(OUTPUT_DATA_PATH);
}
@DataProvider(name = "genotypeConcordanceTestFileData")
public Object[][] getGenotypeConcordanceTestFileData() {
return new Object[][]{
{CEU_TRIOS_SNPS_VCF, "NA12878", CEU_TRIOS_SNPS_VCF, "NA12878", null, null, false, CEU_TRIOS_SNPS_VS_CEU_TRIOS_SNPS_GC},
{CEU_TRIOS_INDELS_VCF, "NA12878", CEU_TRIOS_INDELS_VCF, "NA12878", null, null, false, CEU_TRIOS_INDELS_VS_CEU_TRIOS_INDELS_GC},
{CEU_TRIOS_SNPS_VCF, "NA12878", CEU_TRIOS_SNPS_FIRST_LINE_DIFF_VCF, "NA12878", null, null, false, CEU_TRIOS_SNPS_VS_CEU_TRIOS_SNPS_FIRST_LINE_DIFF_GC},
{CEU_TRIOS_SNPS_VCF, "NA12878", CEU_TRIOS_SNPS_LAST_LINE_DIFF_VCF, "NA12878", null, null, false, CEU_TRIOS_SNPS_VS_CEU_TRIOS_SNPS_LAST_LINE_DIFF_GC},
{CEU_TRIOS_SNPS_VCF, "NA12878", CEU_TRIOS_SNPS_DEL_LINE_VCF, "NA12878", null, null, false, CEU_TRIOS_SNPS_VS_CEU_TRIOS_SNPS_DEL_LINE_GC},
{CEU_TRIOS_SNPS_VCF, "NA12878", CEU_TRIOS_SNPS_VCF, "NA12878", null, null, true, CEU_TRIOS_SNPS_VS_CEU_TRIOS_SNPS_GC_ALL_ROWS},
{CEU_TRIOS_SNPS_VCF, "NA12878", CEU_TRIOS_SNPS_VCF, "NA12891", 40, null, false, CEU_TRIOS_SNPS_VS_CEU_TRIOS_SNPS_GC_MIN_GQ},
{CEU_TRIOS_SNPS_VCF, "NA12878", CEU_TRIOS_SNPS_VCF, "NA12891", null, 40, false, CEU_TRIOS_SNPS_VS_CEU_TRIOS_SNPS_GC_MIN_DP}
};
}
@Test(dataProvider = "genotypeConcordanceTestFileData")
public void testGenotypeConcordance(final File vcf1, final String sample1, final File vcf2, final String sample2,
final Integer minGq, final Integer minDp, final boolean outputAllRows,
final String expectedOutputFileBaseName) throws Exception {
final File outputBaseFileName = new File(OUTPUT_DATA_PATH, "actualGtConc");
final File outputSummaryFile = new File(outputBaseFileName.getAbsolutePath() + GenotypeConcordance.SUMMARY_METRICS_FILE_EXTENSION);
final File outputDetailsFile = new File(outputBaseFileName.getAbsolutePath() + GenotypeConcordance.DETAILED_METRICS_FILE_EXTENSION);
final File outputContingencyFile = new File(outputBaseFileName.getAbsolutePath() + GenotypeConcordance.CONTINGENCY_METRICS_FILE_EXTENSION);
outputSummaryFile.deleteOnExit();
outputDetailsFile.deleteOnExit();
outputContingencyFile.deleteOnExit();
final GenotypeConcordance genotypeConcordance = new GenotypeConcordance();
genotypeConcordance.TRUTH_VCF = vcf1;
genotypeConcordance.TRUTH_SAMPLE = sample1;
genotypeConcordance.CALL_VCF = vcf2;
genotypeConcordance.CALL_SAMPLE = sample2;
if (minGq != null) genotypeConcordance.MIN_GQ = minGq;
if (minDp != null) genotypeConcordance.MIN_DP = minDp;
genotypeConcordance.OUTPUT_ALL_ROWS = outputAllRows;
genotypeConcordance.OUTPUT = outputBaseFileName;
Assert.assertEquals(genotypeConcordance.instanceMain(new String[0]), 0);
assertMetricsFileEqual(outputSummaryFile, new File(TEST_DATA_PATH, expectedOutputFileBaseName + GenotypeConcordance.SUMMARY_METRICS_FILE_EXTENSION));
assertMetricsFileEqual(outputDetailsFile, new File(TEST_DATA_PATH, expectedOutputFileBaseName + GenotypeConcordance.DETAILED_METRICS_FILE_EXTENSION));
assertMetricsFileEqual(outputContingencyFile, new File(TEST_DATA_PATH, expectedOutputFileBaseName + GenotypeConcordance.CONTINGENCY_METRICS_FILE_EXTENSION));
}
private void assertMetricsFileEqual(final File actualMetricsFile, final File expectedMetricsFile) throws FileNotFoundException {
// Actual metrics file
final MetricsFile<GenotypeConcordanceSummaryMetrics, Comparable<?>> actual = new MetricsFile<GenotypeConcordanceSummaryMetrics, Comparable<?>>();
actual.read(new FileReader(actualMetricsFile));
// Expected metrics file
final MetricsFile<GenotypeConcordanceSummaryMetrics, Comparable<?>> expected = new MetricsFile<GenotypeConcordanceSummaryMetrics, Comparable<?>>();
expected.read(new FileReader(expectedMetricsFile));
// Note - cannot use .equals as it calls .areHeadersEqual and they are not since the timestamp (at a minimum is different)
Assert.assertTrue(expected.areMetricsEqual(actual));
Assert.assertTrue(expected.areHistogramsEqual(actual));
}
@Test
public void testGenotypeConcordanceDetails() throws Exception {
final File outputBaseFileName = new File(OUTPUT_DATA_PATH, "actualGtConc");
final File outputSummaryFile = new File(outputBaseFileName.getAbsolutePath() + GenotypeConcordance.SUMMARY_METRICS_FILE_EXTENSION);
final File outputDetailsFile = new File(outputBaseFileName.getAbsolutePath() + GenotypeConcordance.DETAILED_METRICS_FILE_EXTENSION);
outputSummaryFile.deleteOnExit();
outputDetailsFile.deleteOnExit();
final GenotypeConcordance genotypeConcordance = new GenotypeConcordance();
genotypeConcordance.TRUTH_VCF = CEU_TRIOS_SNPS_VCF;
genotypeConcordance.TRUTH_SAMPLE = "NA12878";
genotypeConcordance.CALL_VCF = CEU_TRIOS_SNPS_VCF;
genotypeConcordance.CALL_SAMPLE = "NA12878";
genotypeConcordance.OUTPUT = outputBaseFileName;
Assert.assertEquals(genotypeConcordance.instanceMain(new String[0]), 0);
final Map<TruthAndCallStates, Integer> nonZeroCounts = new HashMap<TruthAndCallStates, Integer>();
nonZeroCounts.put(new TruthAndCallStates(TruthState.HET_REF_VAR1, CallState.HET_REF_VAR1), 104);
nonZeroCounts.put(new TruthAndCallStates(TruthState.HOM_VAR1, CallState.HOM_VAR1), 59);
nonZeroCounts.put(new TruthAndCallStates(TruthState.VC_FILTERED, CallState.VC_FILTERED), 40);
GenotypeConcordanceCounts concordanceCounts = genotypeConcordance.getSnpCounter();
assertNonZeroCountsAgree(concordanceCounts, nonZeroCounts);
final FormatUtil fmt = new FormatUtil();
final GenotypeConcordanceScheme scheme = new GenotypeConcordanceScheme();
concordanceCounts.validateCountsAgainstScheme(scheme);
Assert.assertEquals(fmt.format(concordanceCounts.getSensitivity(scheme, GenotypeConcordanceCounts.HET_TRUTH_STATES)), "1");
Assert.assertEquals(fmt.format(concordanceCounts.Ppv(scheme, GenotypeConcordanceCounts.HET_CALL_STATES)), "1");
Assert.assertEquals(fmt.format(concordanceCounts.getSpecificity(scheme, GenotypeConcordanceCounts.HET_TRUTH_STATES)), "1");
Assert.assertEquals(fmt.format(concordanceCounts.getSensitivity(scheme, GenotypeConcordanceCounts.HOM_VAR_TRUTH_STATES)), "1");
Assert.assertEquals(fmt.format(concordanceCounts.Ppv(scheme, GenotypeConcordanceCounts.HOM_VAR_CALL_STATES)), "1");
Assert.assertEquals(fmt.format(concordanceCounts.getSpecificity(scheme, GenotypeConcordanceCounts.HOM_VAR_TRUTH_STATES)), "?");
Assert.assertEquals(fmt.format(concordanceCounts.getSensitivity(scheme, GenotypeConcordanceCounts.VAR_TRUTH_STATES)), "1");
Assert.assertEquals(fmt.format(concordanceCounts.Ppv(scheme, GenotypeConcordanceCounts.VAR_CALL_STATES)), "1");
Assert.assertEquals(fmt.format(concordanceCounts.getSpecificity(scheme, GenotypeConcordanceCounts.VAR_TRUTH_STATES)), "1");
// Now run it again with different samples
genotypeConcordance.TRUTH_VCF = CEU_TRIOS_SNPS_VCF;
genotypeConcordance.TRUTH_SAMPLE = "NA12878";
genotypeConcordance.CALL_VCF = CEU_TRIOS_SNPS_VCF;
genotypeConcordance.CALL_SAMPLE = "NA12891";
Assert.assertEquals(genotypeConcordance.instanceMain(new String[0]), 0);
nonZeroCounts.clear();
nonZeroCounts.put(new TruthAndCallStates(TruthState.HOM_REF, CallState.HET_REF_VAR1), 31);
nonZeroCounts.put(new TruthAndCallStates(TruthState.HET_REF_VAR1, CallState.HOM_REF), 30);
nonZeroCounts.put(new TruthAndCallStates(TruthState.HET_REF_VAR1, CallState.HET_REF_VAR1), 50);
nonZeroCounts.put(new TruthAndCallStates(TruthState.HET_REF_VAR1, CallState.HOM_VAR1), 24);
nonZeroCounts.put(new TruthAndCallStates(TruthState.HOM_VAR1, CallState.HET_REF_VAR1), 18);
nonZeroCounts.put(new TruthAndCallStates(TruthState.HOM_VAR1, CallState.HOM_VAR1), 41);
nonZeroCounts.put(new TruthAndCallStates(TruthState.VC_FILTERED, CallState.VC_FILTERED), 49);
concordanceCounts = genotypeConcordance.getSnpCounter();
assertNonZeroCountsAgree(concordanceCounts, nonZeroCounts);
Assert.assertEquals(fmt.format(concordanceCounts.getSensitivity(scheme, GenotypeConcordanceCounts.HET_TRUTH_STATES)), "0.711538");
Assert.assertEquals(fmt.format(concordanceCounts.Ppv(scheme, GenotypeConcordanceCounts.HET_CALL_STATES)), "0.686869");
Assert.assertEquals(fmt.format(concordanceCounts.getSpecificity(scheme, GenotypeConcordanceCounts.HET_TRUTH_STATES)), "0.769231");
Assert.assertEquals(fmt.format(concordanceCounts.getSensitivity(scheme, GenotypeConcordanceCounts.HOM_VAR_TRUTH_STATES)), "0.766234");
Assert.assertEquals(fmt.format(concordanceCounts.Ppv(scheme, GenotypeConcordanceCounts.HOM_VAR_CALL_STATES)), "0.730337");
Assert.assertEquals(fmt.format(concordanceCounts.getSpecificity(scheme, GenotypeConcordanceCounts.HOM_VAR_TRUTH_STATES)), "?");
Assert.assertEquals(fmt.format(concordanceCounts.getSensitivity(scheme, GenotypeConcordanceCounts.VAR_TRUTH_STATES)), "0.734807");
Assert.assertEquals(fmt.format(concordanceCounts.Ppv(scheme, GenotypeConcordanceCounts.VAR_CALL_STATES)), "0.707447");
Assert.assertEquals(fmt.format(concordanceCounts.getSpecificity(scheme, GenotypeConcordanceCounts.VAR_TRUTH_STATES)), "0.769231");
}
private void assertNonZeroCountsAgree(final GenotypeConcordanceCounts counter, final Map<TruthAndCallStates, Integer> expectedCountMap) {
for (final TruthState truthState : TruthState.values()) {
for (final CallState callState : CallState.values()) {
Integer expectedCount = expectedCountMap.get(new TruthAndCallStates(truthState, callState));
if (expectedCount == null) expectedCount = 0;
Assert.assertEquals(counter.getCount(truthState, callState), expectedCount.intValue());
}
}
}
@Test
public void testGenotypeConcordanceDetailsWithIntervals() throws Exception {
final File outputBaseFileName = new File(OUTPUT_DATA_PATH, "actualGtConc");
final File outputSummaryFile = new File(outputBaseFileName.getAbsolutePath() + GenotypeConcordance.SUMMARY_METRICS_FILE_EXTENSION);
final File outputDetailsFile = new File(outputBaseFileName.getAbsolutePath() + GenotypeConcordance.DETAILED_METRICS_FILE_EXTENSION);
outputSummaryFile.deleteOnExit();
outputDetailsFile.deleteOnExit();
final GenotypeConcordance genotypeConcordance = new GenotypeConcordance();
genotypeConcordance.TRUTH_VCF = CEU_TRIOS_SNPS_VCF;
genotypeConcordance.TRUTH_SAMPLE = "NA12878";
genotypeConcordance.CALL_VCF = CEU_TRIOS_SNPS_VCF;
genotypeConcordance.CALL_SAMPLE = "NA12878";
genotypeConcordance.INTERVALS = Collections.singletonList(INTERVALS_FILE);
genotypeConcordance.OUTPUT = outputBaseFileName;
Assert.assertEquals(genotypeConcordance.instanceMain(new String[0]), 0);
final Map<TruthAndCallStates, Integer> nonZeroCounts = new HashMap<TruthAndCallStates, Integer>();
nonZeroCounts.put(new TruthAndCallStates(TruthState.HET_REF_VAR1, CallState.HET_REF_VAR1), 1);
nonZeroCounts.put(new TruthAndCallStates(TruthState.VC_FILTERED, CallState.VC_FILTERED), 2);
GenotypeConcordanceCounts concordanceCounts = genotypeConcordance.getSnpCounter();
assertNonZeroCountsAgree(concordanceCounts, nonZeroCounts);
final FormatUtil fmt = new FormatUtil();
final GenotypeConcordanceScheme scheme = new GenotypeConcordanceScheme();
concordanceCounts.validateCountsAgainstScheme(scheme);
Assert.assertEquals(fmt.format(concordanceCounts.getSensitivity(scheme, GenotypeConcordanceCounts.HET_TRUTH_STATES)), "1");
Assert.assertEquals(fmt.format(concordanceCounts.Ppv(scheme, GenotypeConcordanceCounts.HET_CALL_STATES)), "1");
Assert.assertEquals(fmt.format(concordanceCounts.getSpecificity(scheme, GenotypeConcordanceCounts.HET_TRUTH_STATES)), "1");
Assert.assertEquals(fmt.format(concordanceCounts.getSensitivity(scheme, GenotypeConcordanceCounts.HOM_VAR_TRUTH_STATES)), "?");
Assert.assertEquals(fmt.format(concordanceCounts.Ppv(scheme, GenotypeConcordanceCounts.HOM_VAR_CALL_STATES)), "?");
Assert.assertEquals(fmt.format(concordanceCounts.getSpecificity(scheme, GenotypeConcordanceCounts.HOM_VAR_TRUTH_STATES)), "?");
Assert.assertEquals(fmt.format(concordanceCounts.getSensitivity(scheme, GenotypeConcordanceCounts.VAR_TRUTH_STATES)), "1");
Assert.assertEquals(fmt.format(concordanceCounts.Ppv(scheme, GenotypeConcordanceCounts.VAR_CALL_STATES)), "1");
Assert.assertEquals(fmt.format(concordanceCounts.getSpecificity(scheme, GenotypeConcordanceCounts.VAR_TRUTH_STATES)), "1");
// Now run it again with different samples
genotypeConcordance.TRUTH_VCF = CEU_TRIOS_SNPS_VCF;
genotypeConcordance.TRUTH_SAMPLE = "NA12878";
genotypeConcordance.CALL_VCF = CEU_TRIOS_SNPS_VCF;
genotypeConcordance.CALL_SAMPLE = "NA12891";
genotypeConcordance.INTERVALS = Collections.singletonList(INTERVALS_FILE);
Assert.assertEquals(genotypeConcordance.instanceMain(new String[0]), 0);
nonZeroCounts.clear();
nonZeroCounts.put(new TruthAndCallStates(TruthState.HOM_REF, CallState.HET_REF_VAR1), 1);
nonZeroCounts.put(new TruthAndCallStates(TruthState.HET_REF_VAR1, CallState.HET_REF_VAR1), 1);
nonZeroCounts.put(new TruthAndCallStates(TruthState.VC_FILTERED, CallState.VC_FILTERED), 2);
concordanceCounts = genotypeConcordance.getSnpCounter();
assertNonZeroCountsAgree(concordanceCounts, nonZeroCounts);
Assert.assertEquals(fmt.format(concordanceCounts.getSensitivity(scheme, GenotypeConcordanceCounts.HET_TRUTH_STATES)), "1");
Assert.assertEquals(fmt.format(concordanceCounts.Ppv(scheme, GenotypeConcordanceCounts.HET_CALL_STATES)), "0.5");
Assert.assertEquals(fmt.format(concordanceCounts.getSpecificity(scheme, GenotypeConcordanceCounts.HET_TRUTH_STATES)), "1");
Assert.assertEquals(fmt.format(concordanceCounts.getSensitivity(scheme, GenotypeConcordanceCounts.HOM_VAR_TRUTH_STATES)), "?");
Assert.assertEquals(fmt.format(concordanceCounts.Ppv(scheme, GenotypeConcordanceCounts.HOM_VAR_CALL_STATES)), "?");
Assert.assertEquals(fmt.format(concordanceCounts.getSpecificity(scheme, GenotypeConcordanceCounts.HOM_VAR_TRUTH_STATES)), "?");
Assert.assertEquals(fmt.format(concordanceCounts.getSensitivity(scheme, GenotypeConcordanceCounts.VAR_TRUTH_STATES)), "1");
Assert.assertEquals(fmt.format(concordanceCounts.Ppv(scheme, GenotypeConcordanceCounts.VAR_CALL_STATES)), "0.5");
Assert.assertEquals(fmt.format(concordanceCounts.getSpecificity(scheme, GenotypeConcordanceCounts.VAR_TRUTH_STATES)), "1");
}
@DataProvider(name = "genotypeConcordanceDetermineStateDataProvider")
public Object[][] genotypeConcordanceDetermineStateDataProvider() {
final Object[][] originalUnitTestData = new Object[][]{
{Aref, Aref, TruthState.HOM_REF, Aref, Aref, CallState.HOM_REF},
{Aref, Aref, TruthState.HOM_REF, Aref, C, CallState.HET_REF_VAR1},
{Aref, Aref, TruthState.HOM_REF, Aref, G, CallState.HET_REF_VAR1},
{Aref, Aref, TruthState.HOM_REF, Aref, T, CallState.HET_REF_VAR1},
{Aref, Aref, TruthState.HOM_REF, C, G, CallState.HET_VAR1_VAR2},
{Aref, Aref, TruthState.HOM_REF, C, T, CallState.HET_VAR1_VAR2},
{Aref, Aref, TruthState.HOM_REF, G, T, CallState.HET_VAR1_VAR2},
{Aref, Aref, TruthState.HOM_REF, C, C, CallState.HOM_VAR1},
{Aref, Aref, TruthState.HOM_REF, G, G, CallState.HOM_VAR1},
{Aref, Aref, TruthState.HOM_REF, T, T, CallState.HOM_VAR1},
//---
{Aref, C, TruthState.HET_REF_VAR1, Aref, Aref, CallState.HOM_REF},
{Aref, G, TruthState.HET_REF_VAR1, Aref, Aref, CallState.HOM_REF},
{Aref, T, TruthState.HET_REF_VAR1, Aref, Aref, CallState.HOM_REF},
{Aref, C, TruthState.HET_REF_VAR1, Aref, C, CallState.HET_REF_VAR1},
{Aref, C, TruthState.HET_REF_VAR1, Aref, G, CallState.HET_REF_VAR2},
{Aref, C, TruthState.HET_REF_VAR1, Aref, T, CallState.HET_REF_VAR2},
{Aref, G, TruthState.HET_REF_VAR1, Aref, C, CallState.HET_REF_VAR2},
{Aref, G, TruthState.HET_REF_VAR1, Aref, G, CallState.HET_REF_VAR1},
{Aref, G, TruthState.HET_REF_VAR1, Aref, T, CallState.HET_REF_VAR2},
{Aref, T, TruthState.HET_REF_VAR1, Aref, C, CallState.HET_REF_VAR2},
{Aref, T, TruthState.HET_REF_VAR1, Aref, G, CallState.HET_REF_VAR2},
{Aref, T, TruthState.HET_REF_VAR1, Aref, T, CallState.HET_REF_VAR1},
{Aref, C, TruthState.HET_REF_VAR1, C, G, CallState.HET_VAR1_VAR2},
{Aref, C, TruthState.HET_REF_VAR1, C, T, CallState.HET_VAR1_VAR2},
{Aref, C, TruthState.HET_REF_VAR1, G, T, CallState.HET_VAR3_VAR4}, // Why isn't this called HET_VAR2_VAR3???
{Aref, G, TruthState.HET_REF_VAR1, C, G, CallState.HET_VAR1_VAR2},
{Aref, G, TruthState.HET_REF_VAR1, C, T, CallState.HET_VAR3_VAR4},
{Aref, G, TruthState.HET_REF_VAR1, G, T, CallState.HET_VAR1_VAR2},
{Aref, T, TruthState.HET_REF_VAR1, C, G, CallState.HET_VAR3_VAR4},
{Aref, T, TruthState.HET_REF_VAR1, C, T, CallState.HET_VAR1_VAR2},
{Aref, T, TruthState.HET_REF_VAR1, G, T, CallState.HET_VAR1_VAR2},
{Aref, C, TruthState.HET_REF_VAR1, C, C, CallState.HOM_VAR1},
{Aref, C, TruthState.HET_REF_VAR1, G, G, CallState.HOM_VAR2},
{Aref, C, TruthState.HET_REF_VAR1, T, T, CallState.HOM_VAR2},
{Aref, G, TruthState.HET_REF_VAR1, C, C, CallState.HOM_VAR2},
{Aref, G, TruthState.HET_REF_VAR1, G, G, CallState.HOM_VAR1},
{Aref, G, TruthState.HET_REF_VAR1, T, T, CallState.HOM_VAR2},
{Aref, T, TruthState.HET_REF_VAR1, C, C, CallState.HOM_VAR2},
{Aref, T, TruthState.HET_REF_VAR1, G, G, CallState.HOM_VAR2},
{Aref, T, TruthState.HET_REF_VAR1, T, T, CallState.HOM_VAR1},
//---
{C, G, TruthState.HET_VAR1_VAR2, Aref, Aref, CallState.HOM_REF},
{C, T, TruthState.HET_VAR1_VAR2, Aref, Aref, CallState.HOM_REF},
{G, T, TruthState.HET_VAR1_VAR2, Aref, Aref, CallState.HOM_REF},
{C, G, TruthState.HET_VAR1_VAR2, Aref, C, CallState.HET_REF_VAR1},
{C, G, TruthState.HET_VAR1_VAR2, Aref, G, CallState.HET_REF_VAR1},
{C, G, TruthState.HET_VAR1_VAR2, Aref, T, CallState.HET_REF_VAR3},
{C, T, TruthState.HET_VAR1_VAR2, Aref, C, CallState.HET_REF_VAR1},
{C, T, TruthState.HET_VAR1_VAR2, Aref, G, CallState.HET_REF_VAR3},
{C, T, TruthState.HET_VAR1_VAR2, Aref, T, CallState.HET_REF_VAR1},
{G, T, TruthState.HET_VAR1_VAR2, Aref, C, CallState.HET_REF_VAR3},
{G, T, TruthState.HET_VAR1_VAR2, Aref, G, CallState.HET_REF_VAR1},
{G, T, TruthState.HET_VAR1_VAR2, Aref, T, CallState.HET_REF_VAR1},
{C, G, TruthState.HET_VAR1_VAR2, C, C, CallState.HOM_VAR1},
{C, G, TruthState.HET_VAR1_VAR2, G, G, CallState.HOM_VAR1},
{C, G, TruthState.HET_VAR1_VAR2, T, T, CallState.HOM_VAR3},
{C, T, TruthState.HET_VAR1_VAR2, C, C, CallState.HOM_VAR1},
{C, T, TruthState.HET_VAR1_VAR2, G, G, CallState.HOM_VAR3},
{C, T, TruthState.HET_VAR1_VAR2, T, T, CallState.HOM_VAR1},
{G, T, TruthState.HET_VAR1_VAR2, C, C, CallState.HOM_VAR3},
{G, T, TruthState.HET_VAR1_VAR2, G, G, CallState.HOM_VAR1},
{G, T, TruthState.HET_VAR1_VAR2, T, T, CallState.HOM_VAR1},
{C, G, TruthState.HET_VAR1_VAR2, C, G, CallState.HET_VAR1_VAR2},
{C, G, TruthState.HET_VAR1_VAR2, C, T, CallState.HET_VAR1_VAR3},
{C, G, TruthState.HET_VAR1_VAR2, G, T, CallState.HET_VAR1_VAR3},
{C, T, TruthState.HET_VAR1_VAR2, C, G, CallState.HET_VAR1_VAR3},
{C, T, TruthState.HET_VAR1_VAR2, C, T, CallState.HET_VAR1_VAR2},
{C, T, TruthState.HET_VAR1_VAR2, G, T, CallState.HET_VAR1_VAR3},
{G, T, TruthState.HET_VAR1_VAR2, C, G, CallState.HET_VAR1_VAR3},
{G, T, TruthState.HET_VAR1_VAR2, C, T, CallState.HET_VAR1_VAR3},
{G, T, TruthState.HET_VAR1_VAR2, G, T, CallState.HET_VAR1_VAR2},
//---
{C, C, TruthState.HOM_VAR1, Aref, Aref, CallState.HOM_REF},
{G, G, TruthState.HOM_VAR1, Aref, Aref, CallState.HOM_REF},
{T, T, TruthState.HOM_VAR1, Aref, Aref, CallState.HOM_REF},
{C, C, TruthState.HOM_VAR1, Aref, C, CallState.HET_REF_VAR1},
{C, C, TruthState.HOM_VAR1, Aref, G, CallState.HET_REF_VAR2},
{C, C, TruthState.HOM_VAR1, Aref, T, CallState.HET_REF_VAR2},
{G, G, TruthState.HOM_VAR1, Aref, C, CallState.HET_REF_VAR2},
{G, G, TruthState.HOM_VAR1, Aref, G, CallState.HET_REF_VAR1},
{G, G, TruthState.HOM_VAR1, Aref, T, CallState.HET_REF_VAR2},
{T, T, TruthState.HOM_VAR1, Aref, C, CallState.HET_REF_VAR2},
{T, T, TruthState.HOM_VAR1, Aref, G, CallState.HET_REF_VAR2},
{T, T, TruthState.HOM_VAR1, Aref, T, CallState.HET_REF_VAR1},
{C, C, TruthState.HOM_VAR1, C, C, CallState.HOM_VAR1},
{C, C, TruthState.HOM_VAR1, G, G, CallState.HOM_VAR2},
{C, C, TruthState.HOM_VAR1, T, T, CallState.HOM_VAR2},
{G, G, TruthState.HOM_VAR1, C, C, CallState.HOM_VAR2},
{G, G, TruthState.HOM_VAR1, G, G, CallState.HOM_VAR1},
{G, G, TruthState.HOM_VAR1, T, T, CallState.HOM_VAR2},
{T, T, TruthState.HOM_VAR1, C, C, CallState.HOM_VAR2},
{T, T, TruthState.HOM_VAR1, G, G, CallState.HOM_VAR2},
{T, T, TruthState.HOM_VAR1, T, T, CallState.HOM_VAR1},
{C, C, TruthState.HOM_VAR1, C, G, CallState.HET_VAR1_VAR2},
{C, C, TruthState.HOM_VAR1, C, T, CallState.HET_VAR1_VAR2},
{C, C, TruthState.HOM_VAR1, G, T, CallState.HET_VAR3_VAR4},
{G, G, TruthState.HOM_VAR1, C, G, CallState.HET_VAR1_VAR2},
{G, G, TruthState.HOM_VAR1, C, T, CallState.HET_VAR3_VAR4},
{G, G, TruthState.HOM_VAR1, G, T, CallState.HET_VAR1_VAR2},
{T, T, TruthState.HOM_VAR1, C, G, CallState.HET_VAR3_VAR4},
{T, T, TruthState.HOM_VAR1, C, T, CallState.HET_VAR1_VAR2},
{T, T, TruthState.HOM_VAR1, G, T, CallState.HET_VAR1_VAR2},
// Some Indel Cases
{AA, AA, TruthState.HOM_VAR1, AAAA, AAAAA, CallState.HET_VAR3_VAR4},
{AA, AAA, TruthState.HET_VAR1_VAR2, AAAA, AAAAA, CallState.HET_VAR3_VAR4},
// Mixed Cases
{C, AA, TruthState.IS_MIXED, AAAA, AAAAA, CallState.HET_VAR1_VAR2},
{AA, C, TruthState.IS_MIXED, AAAA, AAAAA, CallState.HET_VAR1_VAR2},
{AA, AA, TruthState.HOM_VAR1, C, AAAAA, CallState.IS_MIXED},
{AA, AAA, TruthState.HET_VAR1_VAR2, AAAA, C, CallState.IS_MIXED},
// No Call cases
{Allele.NO_CALL, Aref, TruthState.NO_CALL, Aref, Aref, CallState.HOM_REF},
{Aref, Allele.NO_CALL, TruthState.NO_CALL, Aref, Aref, CallState.HOM_REF},
{Allele.NO_CALL, Allele.NO_CALL, TruthState.NO_CALL, Aref, Aref, CallState.HOM_REF},
{Aref, Aref, TruthState.HOM_REF, Allele.NO_CALL, Aref, CallState.NO_CALL},
{Aref, Aref, TruthState.HOM_REF, Aref, Allele.NO_CALL, CallState.NO_CALL},
{Aref, Aref, TruthState.HOM_REF, Allele.NO_CALL, Allele.NO_CALL, CallState.NO_CALL}
};
// Rebuild a new set of unit test data with all permutations of alleles.
final List<Object[]> allPermutationUnitTestDataList = new ArrayList<Object[]>();
for (final Object[] unitTestData : originalUnitTestData) {
allPermutationUnitTestDataList.add(unitTestData);
final Allele truthAllele1 = (Allele) unitTestData[0];
final Allele truthAllele2 = (Allele) unitTestData[1];
final TruthState expectedTruthState = (TruthState) unitTestData[2];
final Allele callAllele1 = (Allele) unitTestData[3];
final Allele callAllele2 = (Allele) unitTestData[4];
final CallState expectedCallState = (CallState) unitTestData[5];
if (!callAllele1.equals(callAllele2)) {
allPermutationUnitTestDataList.add(new Object[]{truthAllele1, truthAllele2, expectedTruthState, callAllele2, callAllele1, expectedCallState});
}
if (!truthAllele1.equals(truthAllele2)) {
allPermutationUnitTestDataList.add(new Object[]{truthAllele2, truthAllele1, expectedTruthState, callAllele1, callAllele2, expectedCallState});
if (!callAllele1.equals(callAllele2)) {
allPermutationUnitTestDataList.add(new Object[]{truthAllele2, truthAllele1, expectedTruthState, callAllele2, callAllele1, expectedCallState});
}
}
}
Object[][] allPermutationUnitTestData = new Object[allPermutationUnitTestDataList.size()][];
allPermutationUnitTestData = allPermutationUnitTestDataList.toArray(allPermutationUnitTestData);
return allPermutationUnitTestData;
}
@Test(dataProvider = "genotypeConcordanceDetermineStateDataProvider")
public void testGenotypeConcordanceDetermineState(final Allele truthAllele1, final Allele truthAllele2, final TruthState expectedTruthState,
final Allele callAllele1, final Allele callAllele2, final CallState expectedCallState) throws Exception {
final List<Allele> truthAlleles = makeUniqueListOfAlleles(truthAllele1, truthAllele2);
final Genotype truthGt = GenotypeBuilder.create(TRUTH_SAMPLE_NAME, Arrays.asList(truthAllele1, truthAllele2));
final VariantContext truthVariantContext = new VariantContextBuilder("test", snpLoc, snpLocStart, snpLocStop, truthAlleles).genotypes(truthGt).make();
final List<Allele> callAlleles = makeUniqueListOfAlleles(callAllele1, callAllele2);
final Genotype callGt = GenotypeBuilder.create(CALL_SAMPLE_NAME, Arrays.asList(callAllele1, callAllele2));
final VariantContext callVariantContext = new VariantContextBuilder("test", snpLoc, snpLocStart, snpLocStop, callAlleles).genotypes(callGt).make();
testGenotypeConcordanceDetermineState(truthVariantContext, expectedTruthState, callVariantContext, expectedCallState, 0, 0);
}
@Test
public void testGenotypeConcordanceDetermineStateNull() throws Exception {
final List<Allele> alleles = makeUniqueListOfAlleles(Aref, C);
final Genotype gt1 = GenotypeBuilder.create(TRUTH_SAMPLE_NAME, Arrays.asList(Aref, C));
final VariantContext vc1 = new VariantContextBuilder("test", snpLoc, snpLocStart, snpLocStop, alleles).genotypes(gt1).make();
testGenotypeConcordanceDetermineState(null, TruthState.MISSING, null, CallState.MISSING, 0, 0);
testGenotypeConcordanceDetermineState(vc1, TruthState.HET_REF_VAR1, null, CallState.MISSING, 0, 0);
testGenotypeConcordanceDetermineState(null, TruthState.MISSING, vc1, CallState.HET_REF_VAR1, 0, 0);
}
@Test
public void testGenotypeConcordanceDetermineStateFilter() throws Exception {
final Set<String> filters = new HashSet<String>(Arrays.asList("BAD!"));
// Filtering on the variant context
final List<Allele> alleles1 = makeUniqueListOfAlleles(Aref, C);
final Genotype gt1 = GenotypeBuilder.create(TRUTH_SAMPLE_NAME, Arrays.asList(Aref, C));
final VariantContext vcFiltered = new VariantContextBuilder("test", snpLoc, snpLocStart, snpLocStop, alleles1).genotypes(gt1).filters(filters).make();
final List<Allele> alleles2 = makeUniqueListOfAlleles(Aref, T);
final Genotype gt2 = GenotypeBuilder.create(TRUTH_SAMPLE_NAME, Arrays.asList(Aref, T));
final VariantContext vcNotFiltered = new VariantContextBuilder("test", snpLoc, snpLocStart, snpLocStop, alleles2).genotypes(gt2).make();
testGenotypeConcordanceDetermineState(vcFiltered, TruthState.VC_FILTERED, vcNotFiltered, CallState.HET_REF_VAR1, 0, 0);
testGenotypeConcordanceDetermineState(vcNotFiltered, TruthState.HET_REF_VAR1, vcFiltered, CallState.VC_FILTERED, 0, 0);
testGenotypeConcordanceDetermineState(vcFiltered, TruthState.VC_FILTERED, vcFiltered, CallState.VC_FILTERED, 0, 0);
// Filtering on the genotype
final List<String> gtFilters = new ArrayList<String>(Arrays.asList("WICKED"));
final List<Allele> alleles3 = makeUniqueListOfAlleles(Aref, C);
final Genotype gt3 = new GenotypeBuilder(TRUTH_SAMPLE_NAME, Arrays.asList(Aref, C)).filters(gtFilters).make();
final VariantContext vcGtFiltered = new VariantContextBuilder("test", snpLoc, snpLocStart, snpLocStop, alleles3).genotypes(gt3).make();
testGenotypeConcordanceDetermineState(vcGtFiltered, TruthState.GT_FILTERED, vcNotFiltered, CallState.HET_REF_VAR1, 0, 0);
testGenotypeConcordanceDetermineState(vcNotFiltered, TruthState.HET_REF_VAR1, vcGtFiltered, CallState.GT_FILTERED, 0, 0);
testGenotypeConcordanceDetermineState(vcGtFiltered, TruthState.GT_FILTERED, vcGtFiltered, CallState.GT_FILTERED, 0, 0);
}
@Test
public void testGenotypeConcordanceDetermineStateDp() throws Exception {
final List<Allele> allelesNormal = makeUniqueListOfAlleles(Aref, C);
final Genotype gtNormal = GenotypeBuilder.create(TRUTH_SAMPLE_NAME, Arrays.asList(Aref, C));
final VariantContext vcNormal = new VariantContextBuilder("test", snpLoc, snpLocStart, snpLocStop, allelesNormal).genotypes(gtNormal).make();
final List<Allele> allelesLowDp = makeUniqueListOfAlleles(Aref, C);
final Genotype gtLowDp = new GenotypeBuilder(TRUTH_SAMPLE_NAME, Arrays.asList(Aref, C)).DP(4).make();
final VariantContext vcLowDp = new VariantContextBuilder("test", snpLoc, snpLocStart, snpLocStop, allelesLowDp).genotypes(gtLowDp).make();
testGenotypeConcordanceDetermineState(vcLowDp, TruthState.LOW_DP, vcNormal, CallState.HET_REF_VAR1, 0, 20);
testGenotypeConcordanceDetermineState(vcLowDp, TruthState.HET_REF_VAR1, vcLowDp, CallState.HET_REF_VAR1, 0, 2);
testGenotypeConcordanceDetermineState(vcNormal, TruthState.HET_REF_VAR1, vcLowDp, CallState.LOW_DP, 0, 20);
testGenotypeConcordanceDetermineState(vcNormal, TruthState.HET_REF_VAR1, vcLowDp, CallState.HET_REF_VAR1, 0, 2);
testGenotypeConcordanceDetermineState(vcLowDp, TruthState.LOW_DP, vcLowDp, CallState.LOW_DP, 0, 20);
testGenotypeConcordanceDetermineState(vcLowDp, TruthState.HET_REF_VAR1, vcLowDp, CallState.HET_REF_VAR1, 0, 2);
}
@Test
public void testGenotypeConcordanceDetermineStateGq() throws Exception {
final List<Allele> allelesNormal = makeUniqueListOfAlleles(Aref, C);
final Genotype gtNormal = GenotypeBuilder.create(TRUTH_SAMPLE_NAME, Arrays.asList(Aref, C));
final VariantContext vcNormal = new VariantContextBuilder("test", snpLoc, snpLocStart, snpLocStop, allelesNormal).genotypes(gtNormal).make();
final List<Allele> allelesLowGq = makeUniqueListOfAlleles(Aref, C);
final Genotype gtLowGq = new GenotypeBuilder(TRUTH_SAMPLE_NAME, Arrays.asList(Aref, C)).GQ(4).make();
final VariantContext vcLowGq = new VariantContextBuilder("test", snpLoc, snpLocStart, snpLocStop, allelesLowGq).genotypes(gtLowGq).make();
testGenotypeConcordanceDetermineState(vcLowGq, TruthState.LOW_GQ, vcNormal, CallState.HET_REF_VAR1, 20, 0);
testGenotypeConcordanceDetermineState(vcLowGq, TruthState.HET_REF_VAR1, vcLowGq, CallState.HET_REF_VAR1, 2, 0);
testGenotypeConcordanceDetermineState(vcNormal, TruthState.HET_REF_VAR1, vcLowGq, CallState.LOW_GQ, 20, 0);
testGenotypeConcordanceDetermineState(vcNormal, TruthState.HET_REF_VAR1, vcLowGq, CallState.HET_REF_VAR1, 2, 0);
testGenotypeConcordanceDetermineState(vcLowGq, TruthState.LOW_GQ, vcLowGq, CallState.LOW_GQ, 20, 0);
testGenotypeConcordanceDetermineState(vcLowGq, TruthState.HET_REF_VAR1, vcLowGq, CallState.HET_REF_VAR1, 2, 0);
}
/**
* Test method to determine that the expected truth and call states are returned for a pair of truth and call variant contexts.
* @param truthVariantContext
* @param expectedTruthState
* @param callVariantContext
* @param expectedCallState
* @param minGq
* @param minDp
*/
private void testGenotypeConcordanceDetermineState(final VariantContext truthVariantContext, final TruthState expectedTruthState,
final VariantContext callVariantContext, final CallState expectedCallState,
final int minGq, final int minDp) {
final GenotypeConcordance genotypeConcordance = new GenotypeConcordance();
genotypeConcordance.TRUTH_SAMPLE = TRUTH_SAMPLE_NAME;
genotypeConcordance.CALL_SAMPLE = CALL_SAMPLE_NAME;
final TruthAndCallStates truthAndCallStates = genotypeConcordance.determineState(truthVariantContext, TRUTH_SAMPLE_NAME,
callVariantContext, CALL_SAMPLE_NAME, minGq, minDp);
Assert.assertEquals(truthAndCallStates.truthState, expectedTruthState);
Assert.assertEquals(truthAndCallStates.callState, expectedCallState);
}
/**
* Simple method to return a list of unique alleles.
*/
private List<Allele> makeUniqueListOfAlleles(final Allele... alleles) {
final Set<Allele> uniqueAlleles = new HashSet<Allele>();
for (final Allele allele : alleles) {
if (!allele.equals(Allele.NO_CALL)) {
uniqueAlleles.add(allele);
}
}
if (!uniqueAlleles.contains(Aref)) uniqueAlleles.add(Aref);
return new ArrayList<Allele>(uniqueAlleles);
}
}