Include tumor-aware results when results have been rolled-up (sample …

…or library) (#642)


* new CLP CrosscheckFingerprints can crosscheck bams and vcfs
* added option to crosscheck by input file
* added choice of output format: Matrix or Metric File. Metric File outputs contains the LOD score and also the tumor-aware LOD scores.
* Includes tumor-aware results when results are emitted as a metric file
* new CLP ClusterCrosscheckMetrics that will take the metric output of CrosscheckFingerprints and find clusters of groups that connect with a high LOD
* tests refactored
* general purpose graph-clustering algorithm added
* removed deprecated GenotypeReader class
* add a deprecated wrapper named CrosscheckReadgroupFingerprints for backwards continuity
* crosscheck now allows missing RG tags in bam if VALIDATION_STRINGENCY is not STRICT.

build.gradle

@@ -160,7 +160,7 @@ ext.commandClasses = ["picard.sam.AddCommentsToBam", "picard.sam.AddOrReplaceRea
                           "picard.analysis.CollectWgsMetricsWithNonZeroCoverage", "picard.analysis.CompareMetrics", "picard.sam.CompareSAMs",
                           "picard.analysis.artifacts.ConvertSequencingArtifactToOxoG", "picard.sam.CreateSequenceDictionary", "picard.sam.DownsampleSam",
                           "picard.illumina.ExtractIlluminaBarcodes", "picard.sam.markduplicates.EstimateLibraryComplexity", "picard.sam.FastqToSam", "picard.util.FifoBuffer",
-                          "picard.vcf.MendelianViolations.FindMendelianViolations",
                           "picard.sam.FilterSamReads", "picard.vcf.filter.FilterVcf", "picard.sam.FixMateInformation", "picard.sam.GatherBamFiles", "picard.vcf.GatherVcfs",
                           "picard.vcf.GenotypeConcordance", "picard.illumina.IlluminaBasecallsToFastq", "picard.illumina.IlluminaBasecallsToSam", "picard.illumina.CheckIlluminaDirectory",
                           "picard.sam.CheckTerminatorBlock", "picard.util.IntervalListTools", "picard.util.LiftOverIntervalList", "picard.vcf.LiftoverVcf", "picard.vcf.MakeSitesOnlyVcf",

src/main/java/picard/fingerprint/CheckFingerprint.java

@@ -292,7 +292,7 @@ else if (!observedSampleAlias.equals(rec.getSample())) {
         return super.customCommandLineValidation();
     }
 
-    private boolean isBamOrSamFile(final File f) {
         return (BamFileIoUtils.isBamFile(f) || f.getName().endsWith(IOUtil.SAM_FILE_EXTENSION));
     }
 }

src/main/java/picard/fingerprint/ClusterCrosscheckMetrics.java

@@ -0,0 +1,135 @@
+
+/*
+ * The MIT License
+ *
+ * Copyright (c) 2017 The Broad Institute
+ *
+ * Permission is hereby granted, free of charge, to any person obtaining a copy
+ * of this software and associated documentation files (the "Software"), to deal
+ * in the Software without restriction, including without limitation the rights
+ * to use, copy, modify, merge, publish, distribute, sublicense, and/or sell
+ * copies of the Software, and to permit persons to whom the Software is
+ * furnished to do so, subject to the following conditions:
+ *
+ * The above copyright notice and this permission notice shall be included in
+ * all copies or substantial portions of the Software.
+ *
+ * THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR
+ * IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,
+ * FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE
+ * AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER
+ * LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM,
+ * OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN
+ * THE SOFTWARE.
+ */
+
+package picard.fingerprint;
+
+import htsjdk.samtools.metrics.MetricsFile;
+import htsjdk.samtools.util.IOUtil;
+import picard.cmdline.CommandLineProgram;
+import picard.cmdline.CommandLineProgramProperties;
+import picard.cmdline.Option;
+import picard.cmdline.StandardOptionDefinitions;
+import picard.cmdline.programgroups.Fingerprinting;
+import picard.util.GraphUtils;
+
+import java.io.File;
+import java.io.FileNotFoundException;
+import java.io.FileReader;
+import java.util.List;
+import java.util.Map;
+import java.util.Set;
+import java.util.stream.Collectors;
+
+/**
+ * Program to check that all (read-)groups within the set of input files appear to come from the same
+ * individual. Can be used to cross-check libraries, samples, or files.
+ *
+ * @author Yossi Farjoun
+ */
+@CommandLineProgramProperties(
+        usage = "Clusters the results from a CrosscheckFingerprints into groups that are connected according " +
+                "to a large enough LOD score.",
+        usageShort = "Clusters the results of a CrosscheckFingerprints run by LOD score.",
+        programGroup = Fingerprinting.class
+)
+public class ClusterCrosscheckMetrics extends CommandLineProgram {
+
+    @Option(shortName = StandardOptionDefinitions.INPUT_SHORT_NAME,
+            doc = "The cross-check metrics file to be clustered")
+    public File INPUT;
+
+    @Option(shortName = StandardOptionDefinitions.OUTPUT_SHORT_NAME, optional = true,
+            doc = "Optional output file to write metrics to. Default is to write to stdout.")
+    public File OUTPUT;
+
+    @Option(shortName = "LOD",
+            doc = "LOD score to be used as the threshold for clustering.")
+    public double LOD_THRESHOLD = 0;
+
+    @Override
+    protected int doWork() {
+        IOUtil.assertFileIsReadable(INPUT);
+        if(OUTPUT != null) IOUtil.assertFileIsWritable(OUTPUT);
+
+        final MetricsFile<CrosscheckMetric, ?> metricsFile = getMetricsFile();
+
+        try {
+            metricsFile.read(new FileReader(INPUT));
+        } catch (FileNotFoundException e) {
+            e.printStackTrace();
+            return 1;
+        }
+
+        clusterMetrics(metricsFile.getMetrics()).write(OUTPUT);
+
+        return 0;
+    }
+
+    private MetricsFile<ClusteredCrosscheckMetric, ?> clusterMetrics(final List<CrosscheckMetric> metrics) {
+        final GraphUtils.Graph<String> graph = new GraphUtils.Graph<>();
+        metrics.stream()
+                .filter(metric -> metric.LOD_SCORE > LOD_THRESHOLD)
+                .forEach(metric -> {
+                    final String lhsBy = metric.LEFT_GROUP_VALUE;
+                    final String rhsBy = metric.RIGHT_GROUP_VALUE;
+
+                    graph.addEdge(lhsBy, rhsBy);
+                });
+
+        final Map<String, Integer> clusters = graph.cluster();
+
+        // invert map...get map from group integer to list of group_value
+        final Map<Integer, Set<String>> collection = clusters.entrySet().stream()
+                .collect(Collectors.groupingBy(Map.Entry::getValue))
+                .entrySet()
+                .stream()
+                .collect(Collectors
+                        .toMap(Map.Entry::getKey, entry -> entry.getValue()
+                                .stream()
+                                .map(Map.Entry::getKey)
+                                .collect(Collectors.toSet())));
+
+        final MetricsFile<ClusteredCrosscheckMetric, ?> clusteredMetrics = getMetricsFile();
+        // for each cluster, find the metrics that compare groups that are both from the cluster
+        // and add them to the metrics file
+        for (final Map.Entry<Integer, Set<String>> cluster : collection.entrySet()) {
+
+            clusteredMetrics.addAllMetrics(
+                    metrics.stream()
+                            .filter(metric ->
+                                    cluster.getValue().contains(metric.LEFT_GROUP_VALUE) &&
+                                            cluster.getValue().contains(metric.RIGHT_GROUP_VALUE))
+                            .map(metric -> {
+                                final ClusteredCrosscheckMetric clusteredCrosscheckMetric = new ClusteredCrosscheckMetric(metric);
+                                clusteredCrosscheckMetric.CLUSTER = cluster.getKey();
+                                clusteredCrosscheckMetric.CLUSTER_SIZE = cluster.getValue().size();
+
+                                return clusteredCrosscheckMetric;
+                            })
+                            .collect(Collectors.toSet()));
+        }
+        return clusteredMetrics;
+    }
+}

src/main/java/picard/fingerprint/ClusteredCrosscheckMetric.java

@@ -0,0 +1,52 @@
+/*
+ * The MIT License
+ *
+ * Copyright (c) 2015 The Broad Institute
+ *
+ * Permission is hereby granted, free of charge, to any person obtaining a copy
+ * of this software and associated documentation files (the "Software"), to deal
+ * in the Software without restriction, including without limitation the rights
+ * to use, copy, modify, merge, publish, distribute, sublicense, and/or sell
+ * copies of the Software, and to permit persons to whom the Software is
+ * furnished to do so, subject to the following conditions:
+ *
+ * The above copyright notice and this permission notice shall be included in
+ * all copies or substantial portions of the Software.
+ *
+ * THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR
+ * IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,
+ * FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE
+ * AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER
+ * LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM,
+ * OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN
+ * THE SOFTWARE.
+ */
+
+package picard.fingerprint;
+
+import picard.util.ReflectionUtil;
+
+/**
+ * A Metric class to hold the result of clustered crosschecking fingerprints.
+ * The same metric will be used for crosschecking Readgroups, libraries, samples, or files.
+ *
+ * @author Yossi Farjoun
+ */
+
+public class ClusteredCrosscheckMetric extends CrosscheckMetric {
+    // Number indicating the cluster to which the groups within this metric belong.
+    // Metric-lines involving groups that are not in the same cluster should either
+    // be excluded, or given an error-indicating CLUSTER value (perhaps MIN_VALUE?).
+    public Integer CLUSTER;
+
+    public Integer CLUSTER_SIZE;
+
+    public ClusteredCrosscheckMetric() {
+        super();
+    }
+
+    public ClusteredCrosscheckMetric(CrosscheckMetric metric) {
+        super();
+        ReflectionUtil.copyFromBaseClass(metric, this);
+    }
+}