Added numerical-stability tests and updated test data for all ModelSegments single-sample and multiple-sample modes.

src/main/java/org/broadinstitute/hellbender/tools/copynumber/ModelSegments.java

@@ -746,6 +746,12 @@ private void setModesAndValidateArguments() {
                 "Must provide at least one denoised-copy-ratios file or allelic-counts file.");
         Utils.validateArg(!(inputAllelicCountsFiles.isEmpty() && inputNormalAllelicCountsFile != null),
                 "Must provide an allelic-counts file for the case sample to run in matched-normal mode.");
+        Utils.validateArg(!(inputNormalAllelicCountsFile != null && genotypingArguments.minTotalAlleleCountCase > 0),
+                "The minimum total count for filtering allelic counts in case samples must be set to zero in matched-normal mode. " +
+                        "If the effect of statistical noise due to low depth in case samples on segmentation is a concern, " +
+                        "consider using only denoised copy ratios or externally preprocessing allelic-count files " +
+                        "to remove sites that are poorly covered across all samples.");
+
 
         runMode = (inputDenoisedCopyRatiosFiles.size() > 1 || inputAllelicCountsFiles.size() > 1)
                 ? RunMode.MULTIPLE_SAMPLE

src/main/java/org/broadinstitute/hellbender/tools/copynumber/models/AlleleFractionLikelihoods.java

@@ -87,6 +87,8 @@ static double hetLogLikelihood(final AlleleFractionGlobalParameters parameters,
                 - n * log(majorFraction + minorFraction * lambda0RefMinor);
         final double refMinorLogLikelihood = logNotPi + logcRefMinor + Gamma.logGamma(rhoRefMinor) - rhoRefMinor * log(tauRefMinor);
 
+        // changing the factorial implementation below may introduce non-negligible numerical differences;
+        // note https://github.com/broadinstitute/gatk/pull/7652
         final double outlierLogLikelihood = logPi + log10ToLog(log10Factorial(a) + log10Factorial(r) - log10Factorial(a + r + 1));
 
         return NaturalLogUtils.logSumExp(altMinorLogLikelihood, refMinorLogLikelihood, outlierLogLikelihood);

src/test/resources/org/broadinstitute/hellbender/tools/copynumber/model-segments-expected/multiple-sample-ac-nac-tumor-1.af.igv.seg

@@ -0,0 +1,2 @@
+Sample	Chromosome	Start	End	Num_Probes	Segment_Mean
+SM-74P4M-1	20	138125	62871232	827	0.372342

src/test/resources/org/broadinstitute/hellbender/tools/copynumber/model-segments-expected/multiple-sample-ac-nac-tumor-1.cr.igv.seg

@@ -0,0 +1,2 @@
+Sample	Chromosome	Start	End	Num_Probes	Segment_Mean
+SM-74P4M-1	20	138125	62871232	0	NaN

src/test/resources/org/broadinstitute/hellbender/tools/copynumber/model-segments-expected/multiple-sample-ac-nac-tumor-1.cr.seg

@@ -0,0 +1,5 @@
+@HD	VN:1.6
+@SQ	SN:20	LN:63025520	UR:http://www.broadinstitute.org/ftp/pub/seq/references/Homo_sapiens_assembly19.fasta	AS:GRCh37	M5:0dec9660ec1efaaf33281c0d5ea2560f	SP:Homo Sapiens
+@RG	ID:GATKCopyNumber	SM:SM-74P4M-1
+CONTIG	START	END	NUM_POINTS_COPY_RATIO	MEAN_LOG2_COPY_RATIO
+20	138125	62871232	0	NaN