{"action":"created","comment":{"url":"https://api.github.com/repos/broadinstitute/gatk-protected/pulls/comments/60165399","id":60165399,"diff_hunk":"@@ -0,0 +1,300 @@\n+package org.broadinstitute.hellbender.tools.exome;\n+\n+import htsjdk.samtools.ValidationStringency;\n+import htsjdk.samtools.util.IntervalList;\n+import org.apache.logging.log4j.LogManager;\n+import org.apache.logging.log4j.Logger;\n+import org.broadinstitute.hellbender.cmdline.*;\n+import org.broadinstitute.hellbender.cmdline.argumentcollections.ReferenceInputArgumentCollection;\n+import org.broadinstitute.hellbender.cmdline.argumentcollections.RequiredReferenceInputArgumentCollection;\n+import org.broadinstitute.hellbender.cmdline.programgroups.CopyNumberProgramGroup;\n+import org.broadinstitute.hellbender.exceptions.UserException;\n+import org.broadinstitute.hellbender.utils.read.ReadConstants;\n+\n+import java.io.File;\n+\n+/**\n+ * Calls heterozygous sites and output the ref and alt base counts at the called sites.\n+ * A list of SNP sites must be provided.\n+ *\n+ * The tool has three modes. The mode is automatically selected based on the provided arguments:\n+ *\n+ *   NORMAL_ONLY: this mode is chosen if just the normal BAM file is provided. The BALANCED prior\n+ *                is used for estimating the likelihood of het sites.\n+ *\n+ *   TUMOR_ONLY: this mode is chosen if just the tumor BAM file is provided. The HETEROGENEOUS prior\n+ *               is used for estimating the likelihood of het sites.\n+ *\n+ *   NORMAL_TUMOR: this mode is chosen if both normal and tumor BAM files are provided. The BALANCED prior is used\n+ *                 to estimate the likelihood of het sites on the normal reads. The base counts on the same het sites\n+ *                 are collected and reported from the tumor reads.\n+ *\n+ * @author Mehrtash Babadi &lt;mehrtash@brgoadinstitute.org&gt;\n+ */\n+@CommandLineProgramProperties(\n+        summary = \"Calls heterozygous sites and output the ref and alt base counts at the called sites.\",\n+        oneLineSummary = \"Calls heterozygous sites and output the ref and alt base counts at the called sites.\",\n+        programGroup = CopyNumberProgramGroup.class\n+)\n+public final class GetBayesianHetCoverage extends CommandLineProgram {\n+\n+    private final Logger logger = LogManager.getLogger(GetBayesianHetCoverage.class);\n+\n+    protected static final String READ_DEPTH_THRESHOLD_FULL_NAME = \"readDepthThreshold\";\n+    protected static final String READ_DEPTH_THRESHOLD_SHORT_NAME = \"readThresh\";\n+\n+    protected static final String MINIMUM_MAPPING_QUALITY_FULL_NAME = \"minimumMappingQuality\";\n+    protected static final String MINIMUM_MAPPING_QUALITY_SHORT_NAME = \"minMQ\";\n+\n+    protected static final String MINIMUM_BASE_QUALITY_FULL_NAME = \"minimumBaseQuality\";\n+    protected static final String MINIMUM_BASE_QUALITY_SHORT_NAME = \"minBQ\";\n+\n+    protected static final String HET_CALLING_STRINGENCY_FULL_NAME = \"hetCallingStringency\";\n+    protected static final String HET_CALLING_STRINGENCY_SHORT_NAME = \"hetS\";\n+\n+    protected static final String QUADRATURE_ORDER_FULL_NAME = \"quadratureOrder\";\n+    protected static final String QUADRATURE_ORDER_SHORT_NAME = \"quad\";\n+\n+    protected static final String MINIMUM_ABNORMAL_FRACTION_FULL_NAME = \"minimumAbnormalFraction\";\n+    protected static final String MINIMUM_ABNORMAL_FRACTION_SHORT_NAME = \"minAF\";\n+\n+    protected static final String MAXIMUM_ABNORMAL_FRACTION_FULL_NAME = \"maximumAbnormalFraction\";\n+    protected static final String MAXIMUM_ABNORMAL_FRACTION_SHORT_NAME = \"maxAF\";\n+\n+    protected static final String MAXIMUM_COPY_NUMBER_FULL_NAME = \"maximumCopyNumber\";\n+    protected static final String MAXIMUM_COPY_NUMBER_SHORT_NAME = \"maxCN\";\n+\n+    protected static final String ERROR_PROBABILITY_ADJUSTMENT_FACTOR_FULL_NAME = \"errorAdjustmentFactor\";\n+    protected static final String ERROR_PROBABILITY_ADJUSTMENT_FACTOR_SHORT_NAME = \"errFact\";\n+\n+    @ArgumentCollection\n+    protected static final ReferenceInputArgumentCollection REFERENCE_ARGUMENTS =\n+            new RequiredReferenceInputArgumentCollection();\n+\n+    @Argument(\n+            doc = \"Normal BAM file (for normal-only and paired normal-tumor cases).\",\n+            fullName = ExomeStandardArgumentDefinitions.NORMAL_BAM_FILE_LONG_NAME,\n+            shortName = ExomeStandardArgumentDefinitions.NORMAL_BAM_FILE_SHORT_NAME,\n+            optional = true\n+    )\n+    protected File normalBamFile;\n+\n+    @Argument(\n+            doc = \"Tumor BAM file (for tumor-only and paired normal-tumor cases).\",\n+            fullName = ExomeStandardArgumentDefinitions.TUMOR_BAM_FILE_LONG_NAME,\n+            shortName = ExomeStandardArgumentDefinitions.TUMOR_BAM_FILE_SHORT_NAME,\n+            optional = true\n+    )\n+    protected File tumorBamFile;\n+\n+    @Argument(\n+            doc = \"IntervalList file of common SNPs.\",\n+            fullName = ExomeStandardArgumentDefinitions.SNP_FILE_LONG_NAME,\n+            shortName = ExomeStandardArgumentDefinitions.SNP_FILE_SHORT_NAME,\n+            optional = false\n+    )\n+    protected File snpFile;\n+\n+    @Argument(\n+            doc = \"Output file for base counts at called heterozygous SNP sites (normal).\",\n+            fullName = ExomeStandardArgumentDefinitions.NORMAL_ALLELIC_COUNTS_FILE_LONG_NAME,\n+            shortName = ExomeStandardArgumentDefinitions.NORMAL_ALLELIC_COUNTS_FILE_SHORT_NAME,\n+            optional = true\n+    )\n+    protected File normalHetOutputFile;\n+\n+    @Argument(\n+            doc = \"Output file for base counts at called heterozygous SNP sites (tumor).\",\n+            fullName = ExomeStandardArgumentDefinitions.TUMOR_ALLELIC_COUNTS_FILE_LONG_NAME,\n+            shortName = ExomeStandardArgumentDefinitions.TUMOR_ALLELIC_COUNTS_FILE_SHORT_NAME,\n+            optional = true\n+    )\n+    protected File tumorHetOutputFile;\n+\n+    @Argument(\n+            doc = \"Minimum read depth; SNP sites with lower read depths will be ignored.\",\n+            fullName = READ_DEPTH_THRESHOLD_FULL_NAME,\n+            shortName = READ_DEPTH_THRESHOLD_SHORT_NAME,\n+            optional = true\n+    )\n+    protected int readDepthThreshold = 15;\n+\n+    @Argument(\n+            doc = \"Minimum mapping quality; reads with lower quality will be filtered out of pileup.\",\n+            shortName = MINIMUM_MAPPING_QUALITY_SHORT_NAME,\n+            fullName  = MINIMUM_MAPPING_QUALITY_FULL_NAME,\n+            optional = true\n+    )\n+    protected int minimumMappingQuality = 30;\n+\n+    @Argument(\n+            doc = \"Minimum base quality; base calls with lower quality will be filtered out of pileup.\",\n+            shortName = MINIMUM_BASE_QUALITY_SHORT_NAME,\n+            fullName = MINIMUM_BASE_QUALITY_FULL_NAME,\n+            optional = true\n+    )\n+    protected int minimumBaseQuality = 20;\n+\n+    @Argument(\n+            doc = \"Validation stringency for all BAM files read by this program.  Setting stringency to SILENT \" +\n+                    \"can improve performance when processing a BAM file in which variable-length data (read, qualities, tags) \" +\n+                    \"do not otherwise need to be decoded.\",\n+            common=true)\n+    protected ValidationStringency VALIDATION_STRINGENCY = ReadConstants.DEFAULT_READ_VALIDATION_STRINGENCY;\n+\n+    @Argument(\n+            doc = \"Heterozygosous SNP calling stringency.\",\n+            fullName = HET_CALLING_STRINGENCY_FULL_NAME,\n+            shortName = HET_CALLING_STRINGENCY_SHORT_NAME,\n+            optional = false\n+    )\n+    protected double hetCallingStringency = 5;\n+\n+    @Argument(\n+            doc = \"Estimated minimum abnormal cell fraction (for building the allele fraction prior; to be used for \" +\n+                    \"tumor-only cases)\",\n+            fullName = MINIMUM_ABNORMAL_FRACTION_FULL_NAME,\n+            shortName = MINIMUM_ABNORMAL_FRACTION_SHORT_NAME,\n+            optional = true\n+    )\n+    protected double minimumAbnormalFraction = 0.5;\n+\n+    @Argument(\n+            doc = \"Estimated maximum abnormal cell fraction (for building the allele fraction prior; to be used for \" +\n+                    \"tumor-only cases)\",\n+            fullName = MAXIMUM_ABNORMAL_FRACTION_FULL_NAME,\n+            shortName = MAXIMUM_ABNORMAL_FRACTION_SHORT_NAME,\n+            optional = true\n+    )\n+    protected double maximumAbnormalFraction = 0.8;\n+\n+    @Argument(\n+            doc = \"Estimated maximum copy number for either homologs in the abnormal portion of the sample (for \" +\n+                    \"building the allele fraction prior; to be used for tumor-only cases)\",\n+            fullName = MAXIMUM_COPY_NUMBER_FULL_NAME,\n+            shortName = MAXIMUM_COPY_NUMBER_SHORT_NAME,\n+            optional = true\n+    )\n+    protected int maximumCopyNumber = 2;\n+\n+    @Argument(\n+            doc = \"Integration quadrature order; a good choice is the typical read depth (to be used for tumor-only cases)\",\n+            fullName = QUADRATURE_ORDER_FULL_NAME,\n+            shortName = QUADRATURE_ORDER_SHORT_NAME,\n+            optional = true\n+    )\n+    protected int quadratureOrder = 200;\n+\n+    @Argument(\n+            doc = \"(Experimental) error probability adjustment factor (could be any positive value)\",\n+            fullName = ERROR_PROBABILITY_ADJUSTMENT_FACTOR_FULL_NAME,\n+            shortName = ERROR_PROBABILITY_ADJUSTMENT_FACTOR_SHORT_NAME,\n+            optional = true\n+    )\n+    protected double errorProbabilityAdjustmentFactor = 1.0;\n+\n+    private enum HetCoverageJobType {\n+        NORMAL_ONLY, TUMOR_ONLY, NORMAL_TUMOR, NONE\n+    }\n+\n+    @Override\n+    protected Object doWork() {\n+\n+        /* check for illegal arguments */\n+        if (normalBamFile == null && tumorBamFile == null) {\n+            throw new UserException.CommandLineException(\"At least one of normal and tumor BAM files must be provided. Stopping.\");\n+        }\n+        if (normalBamFile != null && normalHetOutputFile == null) {\n+            throw new UserException.CommandLineException(\"If the normal BAM file is provided, the normal Het output file must also be provided. Stopping.\");\n+        }\n+        if (tumorBamFile != null && tumorHetOutputFile == null) {\n+            throw new UserException.CommandLineException(\"If the tumor BAM file is provided, the tumor Het output file must also be provided. Stopping.\");\n+        }\n+\n+        /* determine the job type */\n+        HetCoverageJobType jobType = HetCoverageJobType.NONE;\n+        if (normalBamFile != null && tumorBamFile != null) {\n+            jobType = HetCoverageJobType.NORMAL_TUMOR;\n+            logger.info(\"NORMAL_TUMOR mode selected.\");\n+        }\n+        if (normalBamFile != null && tumorBamFile == null) {\n+            jobType = HetCoverageJobType.NORMAL_ONLY;\n+            logger.info(\"NORMAL_ONLY mode selected.\");\n+        }\n+        if (normalBamFile == null && tumorBamFile != null) {\n+            jobType = HetCoverageJobType.TUMOR_ONLY;\n+            logger.info(\"TUMOR_ONLY mode selected.\");\n+        }\n+\n+        BayesianHetPulldownCalculator normalHetPulldownCalculator, tumorHetPulldownCalculator;\n+        Pulldown normalHetPulldown, tumorHetPulldown;\n+\n+        /* run the job */\n+        switch (jobType) {\n+\n+            case NORMAL_ONLY:\n+","path":"src/main/java/org/broadinstitute/hellbender/tools/exome/GetBayesianHetCoverage.java","position":236,"original_position":236,"commit_id":"1937578df8078be19df3b7aced2788428521d73d","original_commit_id":"1937578df8078be19df3b7aced2788428521d73d","user":{"login":"vruano","id":791104,"avatar_url":"https://avatars.githubusercontent.com/u/791104?v=3","gravatar_id":"","url":"https://api.github.com/users/vruano","html_url":"https://github.com/vruano","followers_url":"https://api.github.com/users/vruano/followers","following_url":"https://api.github.com/users/vruano/following{/other_user}","gists_url":"https://api.github.com/users/vruano/gists{/gist_id}","starred_url":"https://api.github.com/users/vruano/starred{/owner}{/repo}","subscriptions_url":"https://api.github.com/users/vruano/subscriptions","organizations_url":"https://api.github.com/users/vruano/orgs","repos_url":"https://api.github.com/users/vruano/repos","events_url":"https://api.github.com/users/vruano/events{/privacy}","received_events_url":"https://api.github.com/users/vruano/received_events","type":"User","site_admin":false},"body":"In Java, switch cases code normally is not that long. Please, extract private methods out of each case but trying to share common code.","created_at":"2016-04-19T02:20:45Z","updated_at":"2016-04-19T02:20:45Z","html_url":"https://github.com/broadinstitute/gatk-protected/pull/444#discussion_r60165399","pull_request_url":"https://api.github.com/repos/broadinstitute/gatk-protected/pulls/444","_links":{"self":{"href":"https://api.github.com/repos/broadinstitute/gatk-protected/pulls/comments/60165399"},"html":{"href":"https://github.com/broadinstitute/gatk-protected/pull/444#discussion_r60165399"},"pull_request":{"href":"https://api.github.com/repos/broadinstitute/gatk-protected/pulls/444"}}},"pull_request":{"url":"https://api.github.com/repos/broadinstitute/gatk-protected/pulls/444","id":66513881,"html_url":"https://github.com/broadinstitute/gatk-protected/pull/444","diff_url":"https://github.com/broadinstitute/gatk-protected/pull/444.diff","patch_url":"https://github.com/broadinstitute/gatk-protected/pull/444.patch","issue_url":"https://api.github.com/repos/broadinstitute/gatk-protected/issues/444","number":444,"state":"open","locked":false,"title":"\"Bayesian\" Het pulldown","user":{"login":"mbabadi","id":15305869,"avatar_url":"https://avatars.githubusercontent.com/u/15305869?v=3","gravatar_id":"","url":"https://api.github.com/users/mbabadi","html_url":"https://github.com/mbabadi","followers_url":"https://api.github.com/users/mbabadi/followers","following_url":"https://api.github.com/users/mbabadi/following{/other_user}","gists_url":"https://api.github.com/users/mbabadi/gists{/gist_id}","starred_url":"https://api.github.com/users/mbabadi/starred{/owner}{/repo}","subscriptions_url":"https://api.github.com/users/mbabadi/subscriptions","organizations_url":"https://api.github.com/users/mbabadi/orgs","repos_url":"https://api.github.com/users/mbabadi/repos","events_url":"https://api.github.com/users/mbabadi/events{/privacy}","received_events_url":"https://api.github.com/users/mbabadi/received_events","type":"User","site_admin":false},"body":"New Het pulldown tool. At the moment, this CLI tool is separate from the original one (GetHetCoverage). We will eventually either drop the old tool or merge it with this.\r\n\r\nCloses issue #56.","created_at":"2016-04-14T16:25:10Z","updated_at":"2016-04-19T02:20:45Z","closed_at":null,"merged_at":null,"merge_commit_sha":"52bd6122e7df546d83e99c2a330d3a410778602c","assignee":{"login":"vruano","id":791104,"avatar_url":"https://avatars.githubusercontent.com/u/791104?v=3","gravatar_id":"","url":"https://api.github.com/users/vruano","html_url":"https://github.com/vruano","followers_url":"https://api.github.com/users/vruano/followers","following_url":"https://api.github.com/users/vruano/following{/other_user}","gists_url":"https://api.github.com/users/vruano/gists{/gist_id}","starred_url":"https://api.github.com/users/vruano/starred{/owner}{/repo}","subscriptions_url":"https://api.github.com/users/vruano/subscriptions","organizations_url":"https://api.github.com/users/vruano/orgs","repos_url":"https://api.github.com/users/vruano/repos","events_url":"https://api.github.com/users/vruano/events{/privacy}","received_events_url":"https://api.github.com/users/vruano/received_events","type":"User","site_admin":false},"milestone":{"url":"https://api.github.com/repos/broadinstitute/gatk-protected/milestones/7","html_url":"https://github.com/broadinstitute/gatk-protected/milestones/CNV%20Tools%20alpha-2%20release","labels_url":"https://api.github.com/repos/broadinstitute/gatk-protected/milestones/7/labels","id":1392082,"number":7,"title":"CNV Tools alpha-2 release","description":"#### ACNV\r\n\r\n- ACNV improvements, incl. Allelic PoN, CN LOH caller, more plotting, and (if time permits) improving calling balanced segments\r\n- ACNV additional evaluations, incl. \"Amaro's evaluation\"\r\n- case-only ACNV (if time permits)\r\n\r\n#### Germline\r\n- Germline improvements to algorithm\r\n- Germline exome evaluation\r\n- Germline gene panel evaluation\r\n- Tagging germline events in GATK CNV results\r\n\r\n#### WGS\r\n- WGS workflow, including performance (RAM/CPU time) improvements with spark\r\n\r\n#### Other\r\n- GC correction and eval on exome\r\n- Refactoring of copious Target/ReadCount classes (see 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