hmftools.wdl

version 1.0

# Copyright (c) 2020 Leiden University Medical Center
#
# 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.

task Amber {
    input {
        String referenceName
        File referenceBam
        File referenceBamIndex
        String tumorName
        File tumorBam
        File tumorBamIndex
        String outputDir = "./amber"
        File loci
        File referenceFasta
        File referenceFastaFai
        File referenceFastaDict

        Int threads = 2
        String memory = "85GiB"
        String javaXmx = "80G"
        Int timeMinutes = 480
        String dockerImage = "quay.io/biocontainers/hmftools-amber:3.5--0"
    }

    command {
        AMBER -Xmx~{javaXmx} \
        -reference ~{referenceName} \
        -reference_bam ~{referenceBam} \
        -tumor ~{tumorName} \
        -tumor_bam ~{tumorBam} \
        -output_dir ~{outputDir} \
        -threads ~{threads} \
        -ref_genome ~{referenceFasta} \
        -loci ~{loci}
    }

    output {
        File version = "~{outputDir}/amber.version"
        File tumorBafPcf = "~{outputDir}/~{tumorName}.amber.baf.pcf"
        File tumorBafTsv = "~{outputDir}/~{tumorName}.amber.baf.tsv"
        File tumorBafVcf = "~{outputDir}/~{tumorName}.amber.baf.vcf.gz"
        File tumorBafVcfIndex = "~{outputDir}/~{tumorName}.amber.baf.vcf.gz.tbi"
        File tumorContaminationVcf = "~{outputDir}/~{tumorName}.amber.contamination.vcf.gz"
        File tumorContaminationVcfIndex = "~{outputDir}/~{tumorName}.amber.contamination.vcf.gz.tbi"
        File tumorContaminationTsv = "~{outputDir}/~{tumorName}.amber.contamination.tsv"
        File tumorQc = "~{outputDir}/~{tumorName}.amber.qc"
        File normalSnpVcf = "~{outputDir}/~{referenceName}.amber.snp.vcf.gz"
        File normalSnpVcfIndex = "~{outputDir}/~{referenceName}.amber.snp.vcf.gz.tbi"
        Array[File] outputs = [version, tumorBafPcf, tumorBafTsv, tumorBafVcf, tumorBafVcfIndex,
            tumorContaminationVcf, tumorContaminationVcfIndex, tumorContaminationTsv, tumorQc,
            normalSnpVcf, normalSnpVcfIndex]
    }

    runtime {
        memory: memory
        time_minutes: timeMinutes # !UnknownRuntimeKey
        docker: dockerImage
        cpu: threads
    }

    parameter_meta {
        referenceName: {description: "the name of the normal sample.", category: "required"}
        referenceBam: {description: "The normal BAM file.", category: "required"}
        referenceBamIndex: {description: "The index for the normal BAM file.", category: "required"}
        tumorName: {description: "The name of the tumor sample.", category: "required"}
        tumorBam: {description: "The tumor BAM file.", category: "required"}
        tumorBamIndex: {description: "The index for the tumor BAM file.", category: "required"}
        outputDir: {description: "The path to the output directory.", category: "common"}
        loci: {description: "A VCF file containing likely heterozygous sites.", category: "required"}
        referenceFasta: {description: "The reference fasta file.", category: "required"}
        referenceFastaDict: {description: "The sequence dictionary associated with the reference fasta file.",
                             category: "required"}
        referenceFastaFai: {description: "The index for the reference fasta file.", category: "required"}
        threads: {description: "The number of threads the program will use.", category: "advanced"}
        memory: {description: "The amount of memory this job will use.", category: "advanced"}
        javaXmx: {description: "The maximum memory available to the program. Should be lower than `memory` to accommodate JVM overhead.",
                  category: "advanced"}
        timeMinutes: {description: "The maximum amount of time the job will run in minutes.", category: "advanced"}
        dockerImage: {description: "The docker image used for this task. Changing this may result in errors which the developers may choose not to address.",
                      category: "advanced"}
    }
}

task Cobalt {
    input {
        String referenceName
        File referenceBam
        File referenceBamIndex
        String tumorName
        File tumorBam
        File tumorBamIndex
        String outputDir = "./cobalt"
        File gcProfile

        Int threads = 1
        String memory = "5GiB"
        String javaXmx = "4G"
        Int timeMinutes = 480
        String dockerImage = "quay.io/biocontainers/hmftools-cobalt:1.11--0"
    }

    command {
        COBALT -Xmx~{javaXmx} \
        -reference ~{referenceName} \
        -reference_bam ~{referenceBam} \
        -tumor ~{tumorName} \
        -tumor_bam ~{tumorBam} \
        -output_dir ~{outputDir} \
        -threads ~{threads} \
        -gc_profile ~{gcProfile}
    }

    output {
        File version = "~{outputDir}/cobalt.version"
        File normalGcMedianTsv = "~{outputDir}/~{referenceName}.cobalt.gc.median.tsv"
        File normalRationMedianTsv = "~{outputDir}/~{referenceName}.cobalt.ratio.median.tsv"
        File normalRationPcf = "~{outputDir}/~{referenceName}.cobalt.ratio.pcf"
        File tumorGcMedianTsv = "~{outputDir}/~{tumorName}.cobalt.gc.median.tsv"
        File tumorRatioPcf = "~{outputDir}/~{tumorName}.cobalt.ratio.pcf"
        File tumorRatioTsv = "~{outputDir}/~{tumorName}.cobalt.ratio.tsv"
        File tumorChrLen = "~{outputDir}/~{tumorName}.chr.len"
        Array[File] outputs = [version, normalGcMedianTsv, normalRationMedianTsv,
            normalRationPcf, tumorGcMedianTsv, tumorRatioPcf, tumorRatioTsv, tumorChrLen]
    }

    runtime {
        memory: memory
        time_minutes: timeMinutes # !UnknownRuntimeKey
        docker: dockerImage
        cpu: threads
    }

    parameter_meta {
        referenceName: {description: "the name of the normal sample.", category: "required"}
        referenceBam: {description: "The normal BAM file.", category: "required"}
        referenceBamIndex: {description: "The index for the normal BAM file.", category: "required"}
        tumorName: {description: "The name of the tumor sample.", category: "required"}
        tumorBam: {description: "The tumor BAM file.", category: "required"}
        tumorBamIndex: {description: "The index for the tumor BAM file.", category: "required"}
        outputDir: {description: "The path to the output directory.", category: "common"}
        gcProfile: {description: "A file describing the GC profile of the reference genome.", category: "required"}
        threads: {description: "The number of threads the program will use.", category: "advanced"}
        memory: {description: "The amount of memory this job will use.", category: "advanced"}
        javaXmx: {description: "The maximum memory available to the program. Should be lower than `memory` to accommodate JVM overhead.",
                  category: "advanced"}
        timeMinutes: {description: "The maximum amount of time the job will run in minutes.", category: "advanced"}
        dockerImage: {description: "The docker image used for this task. Changing this may result in errors which the developers may choose not to address.",
                      category: "advanced"}
    }
}

task CupGenerateReport {
    input {
        String sampleName
        File cupData
        String outputDir = "./cuppa"

        String memory = "5GiB"
        Int timeMinutes = 10
        String dockerImage = "quay.io/biowdl/cuppa:1.6"
    }

    # This script writes to the directory that the input is located in.
    # Giving the input directly will cause the script to write in the
    # locallized input dir, which may cause issues with write permissions
    # in certain execution engines or backends. We, therefore, make links
    # to a working directory, and give that directory as input instead.
    # We can't just use the outputDir directly. This could be an
    # absolute path in which case the linking might fail due to name
    # collisions. Outputs are copied to the given output dir afterwards.
    command {
        set -e
        mkdir -p ./workdir ~{outputDir}
        ln -s -t workdir ~{cupData}
        CupGenerateReport \
        ~{sampleName} \
        workdir/
        mv -t ~{outputDir} \
        ./workdir/~{sampleName}.cup.report.summary.png \
        ./workdir/~{sampleName}_cup_report.pdf
        if [ -f ./workdir/~{sampleName}.cup.report.features.png ]
          then
            mv -t ~{outputDir} \
            ./workdir/~{sampleName}.cup.report.features.png
        fi
    }

    output {
        File summaryPng = "~{outputDir}/~{sampleName}.cup.report.summary.png"
        File? featuresPng = "~{outputDir}/~{sampleName}.cup.report.features.png"
        File reportPdf = "~{outputDir}/~{sampleName}_cup_report.pdf"
    }

    runtime {
        memory: memory
        time_minutes: timeMinutes # !UnknownRuntimeKey
        docker: dockerImage
    }

    parameter_meta {
        sampleName: {description: "The sample id.", category: "required"}
        cupData: {description: "The output produced by cuppa.", category: "required"}
        outputDir: {description: "The directory the ouput will be placed in.", category: "common"}

        memory: {description: "The amount of memory this job will use.", category: "advanced"}
        timeMinutes: {description: "The maximum amount of time the job will run in minutes.", category: "advanced"}
        dockerImage: {description: "The docker image used for this task. Changing this may result in errors which the developers may choose not to address.",
                      category: "advanced"}
    }
}

task Cuppa {
    input {
        Array[File]+ linxOutput
        Array[File]+ purpleOutput
        String sampleName
        Array[String]+ categories = ["DNA"]
        Array[File]+ referenceData
        File purpleSvVcf
        File purpleSvVcfIndex
        File purpleSomaticVcf
        File purpleSomaticVcfIndex
        String outputDir = "./cuppa"

        String javaXmx = "4G"
        String memory = "5GiB"
        Int timeMinutes = 10
        String dockerImage = "quay.io/biowdl/cuppa:1.6"
    }

    command {
        set -e
        mkdir -p sampleData ~{outputDir}
        ln -s -t sampleData ~{sep=" " linxOutput} ~{sep=" " purpleOutput}
        cuppa -Xmx~{javaXmx} \
        -output_dir ~{outputDir} \
        -output_id ~{sampleName} \
        -categories '~{sep="," categories}' \
        -ref_data_dir ~{sub(referenceData[0], basename(referenceData[0]), "")} \
        -sample_data_dir sampleData \
        -sample_data ~{sampleName} \
        -sample_sv_file ~{purpleSvVcf} \
        -sample_somatic_vcf ~{purpleSomaticVcf}
    }

    output {
        File cupData = "~{outputDir}/~{sampleName}.cup.data.csv"
    }

    runtime {
        memory: memory
        time_minutes: timeMinutes # !UnknownRuntimeKey
        docker: dockerImage
    }

    parameter_meta {
        linxOutput: {description: "The files produced by linx.", category: "required"}
        purpleOutput: {description: "The files produced by purple.", category: "required"}
        sampleName: {description: "The name of the sample.", category: "required"}
        categories: {description: "The classifiers to use.", category: "advanced"}
        referenceData : {description: "The reference data.", category: "required"}
        purpleSvVcf: {description: "The VCF file produced by purple which contains structural variants.", category: "required"}
        purpleSvVcfIndex: {description: "The index of the structural variants VCF file produced by purple.", category: "required"}
        purpleSomaticVcf: {description: "The VCF file produced by purple which contains somatic variants.", category: "required"}
        purpleSomaticVcfIndex: {description: "The index of the somatic VCF file produced by purple.", category: "required"}
        outputDir: {description: "The directory the ouput will be placed in.", category: "common"}
        memory: {description: "The amount of memory this job will use.", category: "advanced"}
        javaXmx: {description: "The maximum memory available to the program. Should be lower than `memory` to accommodate JVM overhead.",
                  category: "advanced"}
        timeMinutes: {description: "The maximum amount of time the job will run in minutes.", category: "advanced"}
        dockerImage: {description: "The docker image used for this task. Changing this may result in errors which the developers may choose not to address.",
                      category: "advanced"}
    }
}

task CuppaChart {
    input {
        String sampleName
        File cupData
        String outputDir = "./cuppa"

        String memory = "4GiB"
        Int timeMinutes = 5
        String dockerImage = "quay.io/biowdl/cuppa:1.6"
    }

    command {
        set -e
        mkdir -p ~{outputDir}
        cuppa-chart \
        -sample ~{sampleName} \
        -sample_data ~{cupData} \
        -output_dir ~{outputDir}
    }

    output {
        File cuppaChart = "~{outputDir}/~{sampleName}.cuppa.chart.png"
        File cuppaConclusion = "~{outputDir}/~{sampleName}.cuppa.conclusion.txt"
    }

    runtime {
        memory: memory
        time_minutes: timeMinutes # !UnknownRuntimeKey
        docker: dockerImage
    }

    parameter_meta {
        sampleName: {description: "The name of the sample.", category:"common"}
        cupData: {description: "The cuppa output.", category: "required"}
        outputDir: {description: "The directory the output will be written to.", category:"common"}
        memory: {description: "The amount of memory this job will use.", category: "advanced"}
        timeMinutes: {description: "The maximum amount of time the job will run in minutes.", category: "advanced"}
        dockerImage: {description: "The docker image used for this task. Changing this may result in errors which the developers may choose not to address.",
                      category: "advanced"}
    }
}

task Gripss {
    input {
        File referenceFasta
        File referenceFastaFai
        File referenceFastaDict
        File knownFusionPairBedpe
        File breakendPon
        File breakpointPon
        String referenceName
        String tumorName
        File vcf
        File vcfIndex
        String outputDir = "./"

        String memory = "17GiB"
        String javaXmx = "16G"
        Int timeMinutes = 50
        String dockerImage = "quay.io/biocontainers/hmftools-gripss:2.0--hdfd78af_0"
    }

    command {
        set -e
        mkdir -p ~{outputDir}
        gripss -Xmx~{javaXmx} -XX:ParallelGCThreads=1 \
        -ref_genome ~{referenceFasta} \
        -known_hotspot_file ~{knownFusionPairBedpe} \
        -pon_sgl_file ~{breakendPon} \
        -pon_sv_file ~{breakpointPon} \
        -reference ~{referenceName} \
        -sample ~{tumorName} \
        -vcf ~{vcf} \
        -output_dir ~{outputDir} \
        -output_id somatic
    }

    output {
        File fullVcf = "~{outputDir}/~{tumorName}.gripss.somatic.vcf.gz"
        File fullVcfIndex = "~{outputDir}/~{tumorName}.gripss.somatic.vcf.gz.tbi"
        File filteredVcf = "~{outputDir}/~{tumorName}.gripss.filtered.somatic.vcf.gz"
        File filteredVcfIndex = "~{outputDir}/~{tumorName}.gripss.filtered.somatic.vcf.gz.tbi"
    }

    runtime {
        memory: memory
        time_minutes: timeMinutes # !UnknownRuntimeKey
        docker: dockerImage
    }

    parameter_meta {
        referenceFasta: {description: "The reference fasta file.", category: "required"}
        referenceFastaDict: {description: "The sequence dictionary associated with the reference fasta file.",
                             category: "required"}
        referenceFastaFai: {description: "The index for the reference fasta file.", category: "required"}
        knownFusionPairBedpe: {description: "Equivalent to the `-known_hotspot_file` option.", category: "required"}
        breakendPon: {description: "Equivalent to the `-pon_sgl_file` option.", category: "required"}
        breakpointPon: {description: "Equivalent to the `-pon_sv_file` option.", category: "required"}
        tumorName: {description: "The name of the tumor sample.", category: "required"}
        referenceName: {description: "The name of the normal sample.", category: "required"}
        vcf: {description: "The input VCF.", category: "required"}
        vcfIndex: {description: "The index for the input VCF.", category: "required"}
        outputDir: {description: "The path the output will be written to.", category:"required"}

        memory: {description: "The amount of memory this job will use.", category: "advanced"}
        javaXmx: {description: "The maximum memory available to the program. Should be lower than `memory` to accommodate JVM overhead.",
                  category: "advanced"}
        timeMinutes: {description: "The maximum amount of time the job will run in minutes.", category: "advanced"}
        dockerImage: {description: "The docker image used for this task. Changing this may result in errors which the developers may choose not to address.",
                      category: "advanced"}
    }
}

task GripssApplicationKt {
    # Obsolete
    input {
        File inputVcf
        String outputPath = "gripss.vcf.gz"
        String tumorName
        String referenceName
        File referenceFasta
        File referenceFastaFai
        File referenceFastaDict
        File breakpointHotspot
        File breakendPon
        File breakpointPon

        String memory = "32GiB"
        String javaXmx = "31G"
        Int timeMinutes = 45
        String dockerImage = "quay.io/biocontainers/hmftools-gripss:1.11--hdfd78af_0"
    }

    command {
        java -Xmx~{javaXmx} -XX:ParallelGCThreads=1 \
        -cp /usr/local/share/hmftools-gripss-1.11-0/gripss.jar \
        com.hartwig.hmftools.gripss.GripssApplicationKt \
        -tumor ~{tumorName} \
        -reference ~{referenceName} \
        -ref_genome ~{referenceFasta} \
        -breakpoint_hotspot ~{breakpointHotspot} \
        -breakend_pon ~{breakendPon} \
        -breakpoint_pon ~{breakpointPon} \
        -input_vcf ~{inputVcf} \
        -output_vcf ~{outputPath} \
        -paired_normal_tumor_ordinals
    }

    output {
        File outputVcf = outputPath
        File outputVcfIndex = outputPath + ".tbi"
    }

    runtime {
        memory: memory
        time_minutes: timeMinutes # !UnknownRuntimeKey
        docker: dockerImage
    }

    parameter_meta {
        inputVcf: {description: "The input VCF.", category: "required"}
        outputPath: {description: "The path where th eoutput VCF will be written.", category: "common"}
        referenceName: {description: "The name of the normal sample.", category: "required"}
        tumorName: {description: "The name of the tumor sample.", category: "required"}
        referenceFasta: {description: "The reference fasta file.", category: "required"}
        referenceFastaDict: {description: "The sequence dictionary associated with the reference fasta file.",
                             category: "required"}
        referenceFastaFai: {description: "The index for the reference fasta file.", category: "required"}
        breakpointHotspot: {description: "Equivalent to the `-breakpoint_hotspot` option.", category: "required"}
        breakendPon: {description: "Equivalent to the `-breakend_pon` option.", category: "required"}
        breakpointPon: {description: "Equivalent to the `-breakpoint_pon` option.", category: "required"}
        memory: {description: "The amount of memory this job will use.", category: "advanced"}
        javaXmx: {description: "The maximum memory available to the program. Should be lower than `memory` to accommodate JVM overhead.",
                  category: "advanced"}
        timeMinutes: {description: "The maximum amount of time the job will run in minutes.", category: "advanced"}
        dockerImage: {description: "The docker image used for this task. Changing this may result in errors which the developers may choose not to address.",
                      category: "advanced"}
    }
}

task GripssHardFilterApplicationKt {
    # Obsolete
    input {
        File inputVcf
        String outputPath = "gripss_hard_filter.vcf.gz"

        String memory = "3GiB"
        String javaXmx = "2G"
        Int timeMinutes = 15
        String dockerImage = "quay.io/biocontainers/hmftools-gripss:1.11--hdfd78af_0"
    }

    command {
        java -Xmx~{javaXmx} -XX:ParallelGCThreads=1 \
        -cp /usr/local/share/hmftools-gripss-1.11-0/gripss.jar \
        com.hartwig.hmftools.gripss.GripssHardFilterApplicationKt \
        -input_vcf ~{inputVcf} \
        -output_vcf ~{outputPath}
    }

    output {
        File outputVcf = outputPath
        File outputVcfIndex = outputPath + ".tbi"
    }

    runtime {
        memory: memory
        time_minutes: timeMinutes # !UnknownRuntimeKey
        docker: dockerImage
    }

    parameter_meta {
        inputVcf: {description: "The input VCF.", category: "required"}
        outputPath: {description: "The path where th eoutput VCF will be written.", category: "common"}
        memory: {description: "The amount of memory this job will use.", category: "advanced"}
        javaXmx: {description: "The maximum memory available to the program. Should be lower than `memory` to accommodate JVM overhead.",
                  category: "advanced"}
        timeMinutes: {description: "The maximum amount of time the job will run in minutes.", category: "advanced"}
        dockerImage: {description: "The docker image used for this task. Changing this may result in errors which the developers may choose not to address.",
                      category: "advanced"}
    }
}

task HealthChecker {
    input {
        String outputDir = "."
        String referenceName
        File referenceFlagstats
        File referenceMetrics
        String tumorName
        File tumorFlagstats
        File tumorMetrics
        Array[File]+ purpleOutput

        String javaXmx = "2G"
        String memory = "3GiB"
        Int timeMinutes = 1
        String dockerImage = "quay.io/biowdl/health-checker:3.2"
    }

    command {
        set -e
        mkdir -p ~{outputDir}
        health-checker -Xmx~{javaXmx} -XX:ParallelGCThreads=1 \
        -reference ~{referenceName} \
        -ref_flagstat_file ~{referenceFlagstats} \
        -ref_wgs_metrics_file ~{referenceMetrics} \
        -tumor ~{tumorName} \
        -tum_flagstat_file ~{tumorFlagstats} \
        -tum_wgs_metrics_file ~{tumorMetrics} \
        -purple_dir ~{sub(purpleOutput[0], basename(purpleOutput[0]), "")} \
        -output_dir ~{outputDir}
        if [ -e '~{outputDir}/~{tumorName}.HealthCheckSucceeded' ]
          then
            echo 'true' > '~{outputDir}/succeeded'
        fi
        if [ -e '~{outputDir}/~{tumorName}.HealthCheckFailed' ]
          then
            echo 'false' > '~{outputDir}/succeeded'
        fi
    }

    output {
        Boolean succeeded = read_boolean("succeeded")
        File outputFile = if succeeded
                          then "~{outputDir}/~{tumorName}.HealthCheckSucceeded"
                          else "~{outputDir}/~{tumorName}.HealthCheckFailed"
    }

    runtime {
        memory: memory
        time_minutes: timeMinutes # !UnknownRuntimeKey
        docker: dockerImage
    }

    parameter_meta {
        outputDir: {description: "The path the output will be written to.", category:"required"}
        referenceName: {description: "The name of the normal sample.", category: "required"}
        referenceFlagstats: {description: "The flagstats for the normal sample.", category: "required"}
        referenceMetrics: {description: "The picard WGS metrics for the normal sample.", category: "required"}
        tumorName: {description: "The name of the tumor sample.", category: "required"}
        tumorFlagstats: {description: "The flagstats for the tumor sample.", category: "required"}
        tumorMetrics: {description: "The picard WGS metrics for the tumor sample.", category: "required"}
        purpleOutput: {description: "The files from purple's output directory.", category: "required"}
        memory: {description: "The amount of memory this job will use.", category: "advanced"}
        javaXmx: {description: "The maximum memory available to the program. Should be lower than `memory` to accommodate JVM overhead.",
                  category: "advanced"}
        timeMinutes: {description: "The maximum amount of time the job will run in minutes.", category: "advanced"}
        dockerImage: {description: "The docker image used for this task. Changing this may result in errors which the developers may choose not to address.",
                      category: "advanced"}
    }
}

task Linx {
    input {
        String sampleName
        File svVcf
        File svVcfIndex
        Array[File]+ purpleOutput
        String refGenomeVersion
        String outputDir = "./linx"
        File fragileSiteCsv
        File lineElementCsv
        File knownFusionCsv
        File driverGenePanel
        Boolean writeAllVisFusions = false
        #The following should be in the same directory.
        File geneDataCsv
        File proteinFeaturesCsv
        File transExonDataCsv
        File transSpliceDataCsv

        String memory = "9GiB"
        String javaXmx = "8G"
        Int timeMinutes = 10
        String dockerImage = "quay.io/biocontainers/hmftools-linx:1.18--hdfd78af_0"
    }

    command {
        linx -Xmx~{javaXmx} -XX:ParallelGCThreads=1 \
        -sample ~{sampleName} \
        -sv_vcf ~{svVcf} \
        -purple_dir ~{sub(purpleOutput[0], basename(purpleOutput[0]), "")} \
        -ref_genome_version ~{refGenomeVersion} \
        -output_dir ~{outputDir} \
        -fragile_site_file ~{fragileSiteCsv} \
        -line_element_file ~{lineElementCsv} \
        -ensembl_data_dir ~{sub(geneDataCsv, basename(geneDataCsv), "")} \
        -check_fusions \
        -known_fusion_file ~{knownFusionCsv} \
        -check_drivers \
        -driver_gene_panel ~{driverGenePanel} \
        -chaining_sv_limit 0 \
        -write_vis_data \
        ~{if writeAllVisFusions then "-write_all_vis_fusions" else ""}
    }

    output {
        File driverCatalog = "~{outputDir}/~{sampleName}.linx.driver.catalog.tsv"
        File linxBreakend = "~{outputDir}/~{sampleName}.linx.breakend.tsv"
        File linxClusters = "~{outputDir}/~{sampleName}.linx.clusters.tsv"
        File linxDrivers = "~{outputDir}/~{sampleName}.linx.drivers.tsv"
        File linxFusion = "~{outputDir}/~{sampleName}.linx.fusion.tsv"
        File linxLinks = "~{outputDir}/~{sampleName}.linx.links.tsv"
        File linxSvs = "~{outputDir}/~{sampleName}.linx.svs.tsv"
        File linxVisCopyNumber = "~{outputDir}/~{sampleName}.linx.vis_copy_number.tsv"
        File linxVisFusion = "~{outputDir}/~{sampleName}.linx.vis_fusion.tsv"
        File linxVisGeneExon = "~{outputDir}/~{sampleName}.linx.vis_gene_exon.tsv"
        File linxVisProteinDomain = "~{outputDir}/~{sampleName}.linx.vis_protein_domain.tsv"
        File linxVisSegments = "~{outputDir}/~{sampleName}.linx.vis_segments.tsv"
        File linxVisSvData = "~{outputDir}/~{sampleName}.linx.vis_sv_data.tsv"
        File linxVersion = "~{outputDir}/linx.version"
        Array[File] outputs = [driverCatalog, linxBreakend, linxClusters, linxDrivers, linxFusion,
                               linxLinks, linxSvs, linxVisCopyNumber, linxVisFusion,
                               linxVisGeneExon, linxVisProteinDomain, linxVisSegments, linxVisSvData,
                               linxVersion]
    }

    runtime {
        time_minutes: timeMinutes # !UnknownRuntimeKey
        docker: dockerImage
        memory: memory
    }

    parameter_meta {
        sampleName: {description: "The name of the sample.", category: "required"}
        svVcf: {description: "A VCF file containing structural variants, produced using GRIDSS, annotated for viral insertions and postprocessed with GRIPSS.", category: "required"}
        svVcfIndex: {description: "Index for the structural variants VCf file.", category: "required"}
        purpleOutput: {description: "The files produced by PURPLE.", category: "required"}
        refGenomeVersion: {description: "The version of the genome assembly used for alignment. Either \"37\" or \"38\".", category: "required"}
        outputDir: {description: "The directory the outputs will be written to.", category: "required"}
        fragileSiteCsv: {description: "A list of known fragile sites.", category: "required"}
        lineElementCsv: {description: "A list of known LINE source regions.", category: "required"}
        knownFusionCsv: {description: "A CSV file describing known fusions.", category: "required"}
        driverGenePanel: {description: "A TSV file describing the driver gene panel.", category: "required"}
        writeAllVisFusions: {description: "Equivalent to the -write_all_vis_fusions flag.", category: "advanced"}
        geneDataCsv: {description: "A  CSV file containing gene information, must be in the same directory as `proteinFeaturesCsv`, `transExonDataCsv` and `transSpliceDataCsv`.", category: "required"}
        proteinFeaturesCsv: {description: "A  CSV file containing protein feature information, must be in the same directory as `geneDataCsv`, `transExonDataCsv` and `transSpliceDataCsv`.", category: "required"}
        transExonDataCsv: {description: "A  CSV file containing transcript exon information, must be in the same directory as `geneDataCsv`, `proteinFeaturesCsv` and `transSpliceDataCsv`.", category: "required"}
        transSpliceDataCsv: {description: "A  CSV file containing transcript splicing information, must be in the same directory as `geneDataCsv`, `proteinFeaturesCsv` and `transExonDataCsv`.", category: "required"}

        memory: {description: "The amount of memory this job will use.", category: "advanced"}
        javaXmx: {description: "The maximum memory available to the program. Should be lower than `memory` to accommodate JVM overhead.",
                  category: "advanced"}
        timeMinutes: {description: "The maximum amount of time the job will run in minutes.", category: "advanced"}
        dockerImage: {description: "The docker image used for this task. Changing this may result in errors which the developers may choose not to address.",
                      category: "advanced"}
    }
}

task LinxVisualisations {
    input {
        String outputDir = "./linx_visualisation"
        String sample
        String refGenomeVersion
        Array[File]+ linxOutput
        Boolean plotReportable = true

        String memory = "9GiB"
        String javaXmx = "8G"
        Int timeMinutes = 1440
        String dockerImage = "quay.io/biocontainers/hmftools-linx:1.18--hdfd78af_0"
    }

    command {
        set -e
        mkdir -p ~{outputDir}
        java -Xmx~{javaXmx} -XX:ParallelGCThreads=1 \
        -cp /usr/local/share/hmftools-linx-1.18-0/sv-linx.jar \
        com.hartwig.hmftools.linx.visualiser.SvVisualiser \
        -sample ~{sample} \
        -ref_genome_version ~{refGenomeVersion} \
        -circos /usr/local/bin/circos \
        -vis_file_dir ~{sub(linxOutput[0], basename(linxOutput[0]), "")} \
        -data_out ~{outputDir}/circos \
        -plot_out ~{outputDir}/plots \
        ~{if plotReportable then "-plot_reportable" else ""}
    }

    output {
        Array[File] circos = glob("~{outputDir}/circos/*")
        Array[File] plots = glob("~{outputDir}/plots/*")
    }

    runtime {
        time_minutes: timeMinutes # !UnknownRuntimeKey
        docker: dockerImage
        memory: memory
    }

    parameter_meta {
        outputDir: {description: "The directory the outputs will be written to.", category: "required"}
        sample: {description: "The sample's name.", category: "required"}
        refGenomeVersion: {description: "The version of the genome assembly used for alignment. Either \"37\" or \"38\".", category: "required"}
        linxOutput: {description: "The directory containing the linx output.", category: "required"}
        plotReportable: {description: "Equivalent to the -plot_reportable flag.", category: "advanced"}

        memory: {description: "The amount of memory this job will use.", category: "advanced"}
        javaXmx: {description: "The maximum memory available to the program. Should be lower than `memory` to accommodate JVM overhead.",
                  category: "advanced"}
        timeMinutes: {description: "The maximum amount of time the job will run in minutes.", category: "advanced"}
        dockerImage: {description: "The docker image used for this task. Changing this may result in errors which the developers may choose not to address.",
                      category: "advanced"}
    }
}

task Orange {
    input {
        String outputDir = "./orange"
        File doidJson
        Array[String] sampleDoids
        String tumorName
        String referenceName
        File referenceMetrics
        File tumorMetrics
        File referenceFlagstats
        File tumorFlagstats
        File sageGermlineGeneCoverageTsv
        File sageSomaticRefSampleBqrPlot
        File sageSomaticTumorSampleBqrPlot
        File purpleGeneCopyNumberTsv
        File purpleGermlineDriverCatalogTsv
        File purpleGermlineVariantVcf
        File purpleGermlineVariantVcfIndex
        Array[File]+ purplePlots
        File purplePurityTsv
        File purpleQcFile
        File purpleSomaticDriverCatalogTsv
        File purpleSomaticVariantVcf
        File purpleSomaticVariantVcfIndex
        File linxFusionTsv
        File linxBreakendTsv
        File linxDriverCatalogTsv
        File linxDriverTsv
        Array[File]+ linxPlots
        File cuppaResultCsv
        File cuppaSummaryPlot
        File? cuppaFeaturePlot
        File chordPredictionTxt
        File peachGenotypeTsv
        File protectEvidenceTsv
        File annotatedVirusTsv
        #File pipelineVersionFile
        File cohortMappingTsv
        File cohortPercentilesTsv

        String memory = "17GiB"
        String javaXmx = "16G"
        Int timeMinutes = 10
        String dockerImage = "quay.io/biowdl/orange:v1.6"
    }

    command {
        set -e
        mkdir -p ~{outputDir}
        orange -Xmx~{javaXmx} -XX:ParallelGCThreads=1 \
        -output_dir ~{outputDir} \
        -doid_json ~{doidJson} \
        -primary_tumor_doids '~{sep=";" sampleDoids}' \
        -max_evidence_level C \
        -tumor_sample_id ~{tumorName} \
        -reference_sample_id ~{referenceName} \
        -ref_sample_wgs_metrics_file ~{referenceMetrics} \
        -tumor_sample_wgs_metrics_file ~{tumorMetrics} \
        -ref_sample_flagstat_file ~{referenceFlagstats} \
        -tumor_sample_flagstat_file ~{tumorFlagstats} \
        -sage_germline_gene_coverage_tsv ~{sageGermlineGeneCoverageTsv} \
        -sage_somatic_ref_sample_bqr_plot ~{sageSomaticRefSampleBqrPlot} \
        -sage_somatic_tumor_sample_bqr_plot ~{sageSomaticTumorSampleBqrPlot} \
        -purple_gene_copy_number_tsv ~{purpleGeneCopyNumberTsv} \
        -purple_germline_driver_catalog_tsv ~{purpleGermlineDriverCatalogTsv} \
        -purple_germline_variant_vcf ~{purpleGermlineVariantVcf} \
        -purple_plot_directory ~{sub(purplePlots[0], basename(purplePlots[0]), "")} \
        -purple_purity_tsv ~{purplePurityTsv} \
        -purple_qc_file ~{purpleQcFile} \
        -purple_somatic_driver_catalog_tsv ~{purpleSomaticDriverCatalogTsv} \
        -purple_somatic_variant_vcf ~{purpleSomaticVariantVcf} \
        -linx_fusion_tsv ~{linxFusionTsv} \
        -linx_breakend_tsv ~{linxBreakendTsv} \
        -linx_driver_catalog_tsv ~{linxDriverCatalogTsv} \
        -linx_driver_tsv ~{linxDriverTsv} \
        -linx_plot_directory ~{sub(linxPlots[0], basename(linxPlots[0]), "")} \
        -cuppa_result_csv ~{cuppaResultCsv} \
        -cuppa_summary_plot ~{cuppaSummaryPlot} \
        ~{"-cuppa_feature_plot " + cuppaFeaturePlot} \
        -chord_prediction_txt ~{chordPredictionTxt} \
        -peach_genotype_tsv ~{peachGenotypeTsv} \
        -protect_evidence_tsv ~{protectEvidenceTsv} \
        -annotated_virus_tsv ~{annotatedVirusTsv} \
        -cohort_mapping_tsv ~{cohortMappingTsv} \
        -cohort_percentiles_tsv ~{cohortPercentilesTsv}
    }
    #TODO may need to be added: -pipeline_version_file ~{pipelineVersionFile}

    output {
        File orangeJson = "~{outputDir}/~{tumorName}.orange.json"
        File orangePdf = "~{outputDir}/~{tumorName}.orange.pdf"
    }

    runtime {
        time_minutes: timeMinutes # !UnknownRuntimeKey
        docker: dockerImage
        memory: memory
    }

    parameter_meta {
        outputDir: {description: "The directory the outputs will be written to.", category: "common"}
        doidJson: {description: "A json with the DOID (Human Disease Ontology) tree.", category: "required"}
        sampleDoids: {description: "The DOIDs (Human Disease Ontology) for the primary tumor.", category: "required"}
        tumorName: {description: "The name of the tumor sample.", category: "required"}
        referenceName: {description: "The name of the normal sample.", category: "required"}
        referenceMetrics: {description: "The picard WGS metrics for the normal sample.", category: "required"}
        tumorMetrics: {description: "The picard WGS metrics for the tumor sample.", category: "required"}
        referenceFlagstats: {description: "The flagstats for the normal sample.", category: "required"}
        tumorFlagstats: {description: "The flagstats for the tumor sample.", category: "required"}
        sageGermlineGeneCoverageTsv: {description: "Gene coverage file produced by the germline sage run.", category: "required"}
        sageSomaticRefSampleBqrPlot: {description: "The reference bqr plot produced by the somatic sage run.", category: "required"}
        sageSomaticTumorSampleBqrPlot: {description: "The reference bqr plot produced by the somatic sage run.", category: "required"}
        purpleGeneCopyNumberTsv: {description: "Copy number tsv produced by purple.", category: "required"}
        purpleGermlineDriverCatalogTsv: {description: "Germline driver catalog produced by purple.", category: "required"}
        purpleGermlineVariantVcf: {description: "Germline variant vcf produced by purple.", category: "required"}
        purplePlots: {description: "The plots generated by purple.", category: "required"}
        purplePurityTsv: {description: "The purity file produced by purple.", category: "required"}
        purpleQcFile: {description: "The qc file produced by purple.", category: "required"}
        purpleSomaticDriverCatalogTsv: {description: "Somatic driver catalog produced by purple.", category: "required"}
        purpleSomaticVariantVcf: {description: "Somatic variant vcf produced by purple.", category: "required"}
        linxFusionTsv: {description: "The fusions tsv produced by linx.", category: "required"}
        linxBreakendTsv: {description: "The breakend tsv produced by linx.", category: "required"}
        linxDriverCatalogTsv: {description: "The driver catalog produced by linx.", category: "required"}
        linxDriverTsv: {description: "The driver tsv produced by linx.", category: "required"}
        linxPlots: {description: "The plots generated by linx.", category: "required"}
        cuppaResultCsv: {description: "The cuppa results csv.", category: "required"}
        cuppaSummaryPlot: {description: "The cuppa summary plot.", category: "required"}
        cuppaFeaturePlot: {description: "The cuppa feature plot.", category: "common"}
        chordPredictionTxt: {description: "Chord prediction results.", category: "required"}
        peachGenotypeTsv: {description: "Genotype tsv produced by peach.", category: "required"}
        protectEvidenceTsv: {description: "Evidence tsv produced by protect.", category: "required"}
        annotatedVirusTsv: {description: "Annotated virus tsv produced by virus-interpreter.", category: "required"}
        #pipelineVersionFile: {description: "", category: "required"}
        cohortMappingTsv: {description: "Cohort mapping file from the HMFTools resources.", category: "required"}
        cohortPercentilesTsv: {description: "Cohort percentile file from the HMFTools resources.", category: "required"}

        memory: {description: "The amount of memory this job will use.", category: "advanced"}
        javaXmx: {description: "The maximum memory available to the program. Should be lower than `memory` to accommodate JVM overhead.",
                  category: "advanced"}
        timeMinutes: {description: "The maximum amount of time the job will run in minutes.", category: "advanced"}
        dockerImage: {description: "The docker image used for this task. Changing this may result in errors which the developers may choose not to address.",
                      category: "advanced"}
    }
}

task Pave {
    input {
        String outputDir = "./"
        String sampleName
        File vcfFile
        File vcfFileIndex
        File referenceFasta
        File referenceFastaFai
        File referenceFastaDict
        String refGenomeVersion
        File driverGenePanel
        #The following should be in the same directory.
        File geneDataCsv
        File proteinFeaturesCsv
        File transExonDataCsv
        File transSpliceDataCsv

        Int timeMinutes = 50
        String javaXmx = "8G"
        String memory = "9GiB"
        String dockerImage = "quay.io/biowdl/pave:v1.0"
    }

    command {
        set -e
        mkdir -p ~{outputDir}
        pave -Xmx~{javaXmx} -XX:ParallelGCThreads=1 \
        -sample ~{sampleName} \
        -vcf_file ~{vcfFile} \
        -output_dir ~{outputDir} \
        -ensembl_data_dir ~{sub(geneDataCsv, basename(geneDataCsv), "")} \
        -ref_genome ~{referenceFasta} \
        -ref_genome_version ~{refGenomeVersion} \
        -driver_gene_panel ~{driverGenePanel}
    }

    output {
        File outputVcf = "~{outputDir}/~{sub(basename(vcfFile), 'vcf.gz$', 'pave.vcf.gz')}"
        File outputVcfIndex = "~{outputDir}/~{sub(basename(vcfFile), 'vcf.gz$', 'pave.vcf.gz.tbi')}"
    }

    runtime {
        time_minutes: timeMinutes # !UnknownRuntimeKey
        docker: dockerImage
        memory: memory
    }

    parameter_meta {
        outputDir: {description: "The directory the outputs will be written to.", category: "required"}
        sampleName: {description: "The name of the sample.", category: "required"}
        vcfFile: {description: "The input VCF file.", category: "required"}
        vcfFileIndex: {description: "The index for the input vcf file.", category: "required"}
        referenceFasta: {description: "The reference fasta file.", category: "required"}
        referenceFastaDict: {description: "The sequence dictionary associated with the reference fasta file.",
                             category: "required"}
        referenceFastaFai: {description: "The index for the reference fasta file.", category: "required"}
        refGenomeVersion: {description: "The version of the genome assembly used for alignment. Either \"HG19\" or \"HG38\".", category: "required"}
        driverGenePanel: {description: "A TSV file describing the driver gene panel.", category: "required"}
        geneDataCsv: {description: "A  CSV file containing gene information, must be in the same directory as `proteinFeaturesCsv`, `transExonDataCsv` and `transSpliceDataCsv`.", category: "required"}
        proteinFeaturesCsv: {description: "A  CSV file containing protein feature information, must be in the same directory as `geneDataCsv`, `transExonDataCsv` and `transSpliceDataCsv`.", category: "required"}
        transExonDataCsv: {description: "A  CSV file containing transcript exon information, must be in the same directory as `geneDataCsv`, `proteinFeaturesCsv` and `transSpliceDataCsv`.", category: "required"}
        transSpliceDataCsv: {description: "A  CSV file containing transcript splicing information, must be in the same directory as `geneDataCsv`, `proteinFeaturesCsv` and `transExonDataCsv`.", category: "required"}

        memory: {description: "The amount of memory this job will use.", category: "advanced"}
        javaXmx: {description: "The maximum memory available to the program. Should be lower than `memory` to accommodate JVM overhead.",
                  category: "advanced"}
        timeMinutes: {description: "The maximum amount of time the job will run in minutes.", category: "advanced"}
        dockerImage: {description: "The docker image used for this task. Changing this may result in errors which the developers may choose not to address.",
                      category: "advanced"}
    }
}

task Protect {
    input {
        String refGenomeVersion
        String tumorName
        String referenceName
        Array[String]+ sampleDoids
        String outputDir = "."
        Array[File]+ serveActionability
        File doidJson
        File purplePurity
        File purpleQc
        File purpleDriverCatalogSomatic
        File purpleDriverCatalogGermline
        File purpleSomaticVariants
        File purpleSomaticVariantsIndex
        File purpleGermlineVariants
        File purpleGermlineVariantsIndex
        File purpleGeneCopyNumber
        File linxFusion
        File linxBreakend
        File linxDriversCatalog
        File chordPrediction
        File annotatedVirus

        String memory = "9GiB"
        String javaXmx = "8G"
        Int timeMinutes = 60
        String dockerImage = "quay.io/biowdl/protect:v2.0"
    }

    command {
        protect -Xmx~{javaXmx} \
        -ref_genome_version ~{refGenomeVersion} \
        -tumor_sample_id ~{tumorName} \
        -reference_sample_id ~{referenceName} \
        -primary_tumor_doids '~{sep=";" sampleDoids}' \
        -output_dir ~{outputDir} \
        -serve_actionability_dir ~{sub(serveActionability[0], basename(serveActionability[0]), "")} \
        -doid_json ~{doidJson} \
        -purple_purity_tsv ~{purplePurity} \
        -purple_qc_file ~{purpleQc} \
        -purple_somatic_driver_catalog_tsv ~{purpleDriverCatalogSomatic} \
        -purple_germline_driver_catalog_tsv ~{purpleDriverCatalogGermline} \
        -purple_somatic_variant_vcf ~{purpleSomaticVariants} \
        -purple_germline_variant_vcf ~{purpleGermlineVariants} \
        -purple_gene_copy_number_tsv ~{purpleGeneCopyNumber} \
        -linx_fusion_tsv ~{linxFusion} \
        -linx_breakend_tsv ~{linxBreakend} \
        -linx_driver_catalog_tsv ~{linxDriversCatalog} \
        -chord_prediction_txt ~{chordPrediction} \
        -annotated_virus_tsv ~{annotatedVirus}
    }

    output {
        File protectTsv = "~{outputDir}/~{tumorName}.protect.tsv"
    }

    runtime {
        time_minutes: timeMinutes # !UnknownRuntimeKey
        docker: dockerImage
        memory: memory
    }

    parameter_meta {
        refGenomeVersion: {description: "The version of the genome assembly used for alignment. Either \"37\" or \"38\".", category: "required"}
        tumorName: {description: "The name of the tumor sample.", category: "required"}
        referenceName: {description: "The name of the normal sample.", category: "required"}
        sampleDoids: {description: "The DOIDs (Human Disease Ontology) for the primary tumor.", category: "required"}
        outputDir: {description: "The directory the outputs will be written to.", category: "required"}
        serveActionability: {description: "The actionability files generated by hmftools' serve.", category: "required"}
        doidJson: {description: "A json with the DOID (Human Disease Ontology) tree.", category: "required"}
        purplePurity: {description: "The purity file generated by purple.", category: "required"}
        purpleQc: {description: "The QC file generated by purple.", category: "required"}
        purpleDriverCatalogSomatic: {description: "The somatic driver catalog generated by purple.", category: "required"}
        purpleDriverCatalogGermline: {description: "The germline driver catalog generated by purple.", category: "required"}
        purpleSomaticVariants: {description: "The somatic VCF generated by purple.", category: "required"}
        purpleSomaticVariantsIndex: {description: "The index for the somatic VCF generated by purple.", category: "required"}
        purpleGermlineVariants: {description: "The germline VCF generated by purple.", category: "required"}
        purpleGermlineVariantsIndex: {description: "The index of the germline VCF generated by purple.", category: "required"}
        purpleGeneCopyNumber: {description: "The gene copy number file generated by purple.", category: "required"}
        linxFusion: {description: "The fusion file generated by linx.", category: "required"}
        linxBreakend: {description: "The breakend file generated by linx.", category: "required"}
        linxDriversCatalog: {description: "The driver catalog generated generated by linx.", category: "required"}
        chordPrediction: {description: "The chord prediction file.", category: "required"}
        annotatedVirus: {description: "The virus-interpreter output.", category: "required"}

        memory: {description: "The amount of memory this job will use.", category: "advanced"}
        javaXmx: {description: "The maximum memory available to the program. Should be lower than `memory` to accommodate JVM overhead.",
                  category: "advanced"}
        timeMinutes: {description: "The maximum amount of time the job will run in minutes.", category: "advanced"}
        dockerImage: {description: "The docker image used for this task. Changing this may result in errors which the developers may choose not to address.",
                      category: "advanced"}
    }
}

task Purple {
    input {
        String referenceName
        String tumorName
        String outputDir = "./purple"
        Array[File]+ amberOutput
        Array[File]+ cobaltOutput
        File gcProfile
        File somaticVcf
        File germlineVcf
        File filteredSvVcf
        File filteredSvVcfIndex
        File fullSvVcf
        File fullSvVcfIndex
        File referenceFasta
        File referenceFastaFai
        File referenceFastaDict
        File driverGenePanel
        File somaticHotspots
        File germlineHotspots
        Float? highlyDiploidPercentage
        Float? somaticMinPuritySpread
        #The following should be in the same directory.
        File geneDataCsv
        File proteinFeaturesCsv
        File transExonDataCsv
        File transSpliceDataCsv

        Int threads = 1
        Int timeMinutes = 30
        String memory = "9GiB"
        String javaXmx = "8G"
        # clone of quay.io/biocontainers/hmftools-purple:3.2--hdfd78af_0 with 'ln -s /usr/local/lib/libwebp.so.7 /usr/local/lib/libwebp.so.6'
        String dockerImage = "quay.io/biowdl/hmftools-purple:3.2"
    }

    command {
        PURPLE -Xmx~{javaXmx} \
        -reference ~{referenceName} \
        -germline_vcf ~{germlineVcf} \
        -germline_hotspots ~{germlineHotspots} \
        -tumor ~{tumorName} \
        -output_dir ~{outputDir} \
        -amber ~{sub(amberOutput[0], basename(amberOutput[0]), "")} \
        -cobalt ~{sub(cobaltOutput[0], basename(cobaltOutput[0]), "")} \
        -gc_profile ~{gcProfile} \
        -somatic_vcf ~{somaticVcf} \
        -structural_vcf ~{filteredSvVcf} \
        -sv_recovery_vcf ~{fullSvVcf} \
        -circos /usr/local/bin/circos \
        -ref_genome ~{referenceFasta} \
        -ensembl_data_dir ~{sub(geneDataCsv, basename(geneDataCsv), "")} \
        -run_drivers \
        -somatic_hotspots ~{somaticHotspots} \
        -driver_gene_panel ~{driverGenePanel} \
        ~{"-highly_diploid_percentage " + highlyDiploidPercentage} \
        ~{"-somatic_min_purity_spread " + somaticMinPuritySpread} \
        -threads ~{threads}
    }

    output {
        File driverCatalogGermlineTsv = "~{outputDir}/~{tumorName}.driver.catalog.germline.tsv"
        File driverCatalogSomaticTsv = "~{outputDir}/~{tumorName}.driver.catalog.somatic.tsv"
        File purpleCnvGeneTsv = "~{outputDir}/~{tumorName}.purple.cnv.gene.tsv"
        File purpleCnvSomaticTsv = "~{outputDir}/~{tumorName}.purple.cnv.somatic.tsv"
        File purpleGermlineDeletionTsv = "~{outputDir}/~{tumorName}.purple.germline.deletion.tsv"
        File purpleGermlineVcf = "~{outputDir}/~{tumorName}.purple.germline.vcf.gz"
        File purpleGermlineVcfIndex = "~{outputDir}/~{tumorName}.purple.germline.vcf.gz.tbi"
        File purplePurityRangeTsv = "~{outputDir}/~{tumorName}.purple.purity.range.tsv"
        File purplePurityTsv = "~{outputDir}/~{tumorName}.purple.purity.tsv"
        File purpleQc = "~{outputDir}/~{tumorName}.purple.qc"
        File purpleSegmentTsv = "~{outputDir}/~{tumorName}.purple.segment.tsv"
        File purpleSomaticClonalityTsv = "~{outputDir}/~{tumorName}.purple.somatic.clonality.tsv"
        File purpleSomaticHistTsv = "~{outputDir}/~{tumorName}.purple.somatic.hist.tsv"
        File purpleSomaticVcf = "~{outputDir}/~{tumorName}.purple.somatic.vcf.gz"
        File purpleSomaticVcfIndex = "~{outputDir}/~{tumorName}.purple.somatic.vcf.gz.tbi"
        File purpleSvVcf = "~{outputDir}/~{tumorName}.purple.sv.vcf.gz"
        File purpleSvVcfIndex = "~{outputDir}/~{tumorName}.purple.sv.vcf.gz.tbi"
        File purpleVersion = "~{outputDir}/purple.version"
        File circosPlot = "~{outputDir}/plot/~{tumorName}.circos.png"
        File copynumberPlot = "~{outputDir}/plot/~{tumorName}.copynumber.png"
        File inputPlot = "~{outputDir}/plot/~{tumorName}.input.png"
        File mapPlot = "~{outputDir}/plot/~{tumorName}.map.png"
        File purityRangePlot = "~{outputDir}/plot/~{tumorName}.purity.range.png"
        File segmentPlot = "~{outputDir}/plot/~{tumorName}.segment.png"
        File somaticClonalityPlot = "~{outputDir}/plot/~{tumorName}.somatic.clonality.png"
        File somaticPlot = "~{outputDir}/plot/~{tumorName}.somatic.png"
        File? somaticRainfallPlot = "~{outputDir}/plot/~{tumorName}.somatic.rainfall.png"
        File circosNormalRatio = "~{outputDir}/circos/~{referenceName}.ratio.circos"
        File circosBaf = "~{outputDir}/circos/~{tumorName}.baf.circos"
        File circosConf = "~{outputDir}/circos/~{tumorName}.circos.conf"
        File circosCnv = "~{outputDir}/circos/~{tumorName}.cnv.circos"
        File circosIndel = "~{outputDir}/circos/~{tumorName}.indel.circos"
        File circosInputConf = "~{outputDir}/circos/~{tumorName}.input.conf"
        File circosLink = "~{outputDir}/circos/~{tumorName}.link.circos"
        File circosMap = "~{outputDir}/circos/~{tumorName}.map.circos"
        File circosTumorRatio = "~{outputDir}/circos/~{tumorName}.ratio.circos"
        File circosSnp = "~{outputDir}/circos/~{tumorName}.snp.circos"
        File circosGaps = "~{outputDir}/circos/gaps.txt"
        Array[File] outputs = [driverCatalogSomaticTsv, purpleCnvGeneTsv,
            purpleCnvSomaticTsv, purplePurityRangeTsv, purplePurityTsv, purpleQc,
            purpleSegmentTsv, purpleSomaticClonalityTsv, purpleSomaticHistTsv,
            purpleSomaticVcf, purpleSomaticVcfIndex, purpleSvVcf, purpleSvVcfIndex,
            purpleVersion, purpleGermlineVcf, purpleGermlineVcfIndex, driverCatalogGermlineTsv]
        Array[File] plots = select_all([circosPlot, copynumberPlot, inputPlot, mapPlot, purityRangePlot,
            segmentPlot, somaticClonalityPlot, somaticPlot, somaticRainfallPlot])
        Array[File] circos = [circosNormalRatio, circosConf, circosIndel, circosLink,
            circosTumorRatio, circosGaps, circosBaf, circosCnv, circosInputConf, circosMap,
            circosSnp]
    }

    runtime {
        time_minutes: timeMinutes # !UnknownRuntimeKey
        cpu: threads
        docker: dockerImage
        memory: memory
    }

    parameter_meta {
        referenceName: {description: "the name of the normal sample.", category: "required"}
        tumorName: {description: "The name of the tumor sample.", category: "required"}
        outputDir: {description: "The path to the output directory.", category: "common"}
        amberOutput: {description: "The output files of hmftools amber.", category: "required"}
        cobaltOutput: {description: "The output files of hmftools cobalt", category: "required"}
        gcProfile: {description: "A file describing the GC profile of the reference genome.", category: "required"}
        somaticVcf: {description: "The somatic variant calling results.", category: "required"}
        germlineVcf: {description: "The germline variant calling results.", category: "required"}
        filteredSvVcf: {description: "The filtered structural variant calling results.", category: "required"}
        fullSvVcf: {description: "The unfiltered structural variant calling results.", category: "required"}
        referenceFasta: {description: "The reference fasta file.", category: "required"}
        referenceFastaDict: {description: "The sequence dictionary associated with the reference fasta file.",
                             category: "required"}
        referenceFastaFai: {description: "The index for the reference fasta file.", category: "required"}
        driverGenePanel: {description: "A TSV file describing the driver gene panel.", category: "required"}
        somaticHotspots: {description: "A vcf file with hotspot somatic variant sites.", category: "required"}
        germlineHotspots: {description: "A vcf file with hotspot germline variant sites.", category: "required"}
        highlyDiploidPercentage: {description: "Equivalent to PURPLE's `-highly_diploid_percentage` option.", category: "advanced"}
        somaticMinPuritySpread: {description: "Equivalent to PURPLE's `-somatic_min_purity_spread` option.", category: "advanced"}
        geneDataCsv: {description: "A  CSV file containing gene information, must be in the same directory as `proteinFeaturesCsv`, `transExonDataCsv` and `transSpliceDataCsv`.", category: "required"}
        proteinFeaturesCsv: {description: "A  CSV file containing protein feature information, must be in the same directory as `geneDataCsv`, `transExonDataCsv` and `transSpliceDataCsv`.", category: "required"}
        transExonDataCsv: {description: "A  CSV file containing transcript exon information, must be in the same directory as `geneDataCsv`, `proteinFeaturesCsv` and `transSpliceDataCsv`.", category: "required"}
        transSpliceDataCsv: {description: "A  CSV file containing transcript splicing information, must be in the same directory as `geneDataCsv`, `proteinFeaturesCsv` and `transExonDataCsv`.", category: "required"}


        threads: {description: "The number of threads the program will use.", category: "advanced"}
        memory: {description: "The amount of memory this job will use.", category: "advanced"}
        javaXmx: {description: "The maximum memory available to the program. Should be lower than `memory` to accommodate JVM overhead.",
                  category: "advanced"}
        timeMinutes: {description: "The maximum amount of time the job will run in minutes.", category: "advanced"}
        dockerImage: {description: "The docker image used for this task. Changing this may result in errors which the developers may choose not to address.",
                      category: "advanced"}
    }
}

task Sage {
    input {
        String tumorName
        File tumorBam
        File tumorBamIndex
        File referenceFasta
        File referenceFastaDict
        File referenceFastaFai
        File hotspots
        File panelBed
        File highConfidenceBed
        Boolean hg38 = false
        Boolean panelOnly = false
        String outputPath = "./sage.vcf.gz"

        String? referenceName
        File? referenceBam
        File? referenceBamIndex
        Int? hotspotMinTumorQual
        Int? panelMinTumorQual
        Int? hotspotMaxGermlineVaf
        Int? hotspotMaxGermlineRelRawBaseQual
        Int? panelMaxGermlineVaf
        Int? panelMaxGermlineRelRawBaseQual
        String? mnvFilterEnabled
        File? coverageBed

        Int threads = 32
        String javaXmx = "16G"
        String memory = "20GiB"
        Int timeMinutes = 720
        String dockerImage = "quay.io/biocontainers/hmftools-sage:2.8--hdfd78af_1"
    }

    command {
        SAGE -Xmx~{javaXmx} -XX:ParallelGCThreads=1 \
        -tumor ~{tumorName} \
        -tumor_bam ~{tumorBam} \
        ~{"-reference " + referenceName} \
        ~{"-reference_bam " + referenceBam} \
        -ref_genome ~{referenceFasta} \
        -hotspots ~{hotspots} \
        -panel_bed ~{panelBed} \
        -high_confidence_bed ~{highConfidenceBed} \
        -assembly ~{true="hg38" false="hg19" hg38} \
        ~{"-hotspot_min_tumor_qual " + hotspotMinTumorQual} \
        ~{"-panel_min_tumor_qual " + panelMinTumorQual} \
        ~{"-hotspot_max_germline_vaf " + hotspotMaxGermlineVaf} \
        ~{"-hotspot_max_germline_rel_raw_base_qual " + hotspotMaxGermlineRelRawBaseQual} \
        ~{"-panel_max_germline_vaf " + panelMaxGermlineVaf} \
        ~{"-panel_max_germline_rel_raw_base_qual " + panelMaxGermlineRelRawBaseQual} \
        ~{"-mnv_filter_enabled " + mnvFilterEnabled} \
        ~{"-coverage_bed " + coverageBed} \
        ~{true="-panel_only" false="" panelOnly} \
        -threads ~{threads} \
        -out ~{outputPath}
    }

    output {
        File outputVcf = outputPath
        File outputVcfIndex = outputPath + ".tbi"
        File? referenceSageBqrPng = "~{referenceName}.sage.bqr.png"
        File? referenceSageBqrTsv = "~{referenceName}.sage.bqr.tsv"
        File tumorSageBqrPng = "~{tumorName}.sage.bqr.png"
        File tumorSageBqrTsv = "~{tumorName}.sage.bqr.tsv"
        File sageGeneCoverageTsv = "~{tumorName}.sage.gene.coverage.tsv"
    }

    runtime {
        time_minutes: timeMinutes # !UnknownRuntimeKey
        cpu: threads
        docker: dockerImage
        memory: memory
    }

    parameter_meta {
        tumorName: {description: "The name of the tumor sample.", category: "required"}
        tumorBam: {description: "The BAM file for the tumor sample.", category: "required"}
        tumorBamIndex: {description: "The index of the BAM file for the tumor sample.", category: "required"}
        referenceName: {description: "The name of the normal/reference sample.", category: "common"}
        referenceBam: {description: "The BAM file for the normal sample.", category: "common"}
        referenceBamIndex: {description: "The index of the BAM file for the normal sample.", category: "common"}
        referenceFasta: {description: "The reference fasta file.", category: "required"}
        referenceFastaDict: {description: "The sequence dictionary associated with the reference fasta file.",
                             category: "required"}
        referenceFastaFai: {description: "The index for the reference fasta file.", category: "required"}
        hotspots: {description: "A vcf file with hotspot variant sites.", category: "required"}
        panelBed: {description: "A bed file describing coding regions to search for in frame indels.", category: "required"}
        highConfidenceBed: {description: "A bed files describing high confidence mapping regions.", category: "required"}
        hotspotMinTumorQual: {description: "Equivalent to sage's `hotspot_min_tumor_qual` option.", category: "advanced"}
        panelMinTumorQual: {description: "Equivalent to sage's `panel_min_tumor_qual` option.", category: "advanced"}
        hotspotMaxGermlineVaf: {description: "Equivalent to sage's `hotspot_max_germline_vaf` option.", category: "advanced"}
        hotspotMaxGermlineRelRawBaseQual: {description: "Equivalent to sage's `hotspot_max_germline_rel_raw_base_qual` option.", category: "advanced"}
        panelMaxGermlineVaf: {description: "Equivalent to sage's `panel_max_germline_vaf` option.", category: "advanced"}
        panelMaxGermlineRelRawBaseQual: {description: "Equivalent to sage's `panel_max_germline_vaf` option.", category: "advanced"}
        mnvFilterEnabled: {description: "Equivalent to sage's `mnv_filter_enabled` option.", category: "advanced"}

        memory: {description: "The amount of memory this job will use.", category: "advanced"}
        javaXmx: {description: "The maximum memory available to the program. Should be lower than `memory` to accommodate JVM overhead.",
                  category: "advanced"}
        timeMinutes: {description: "The maximum amount of time the job will run in minutes.", category: "advanced"}
        dockerImage: {description: "The docker image used for this task. Changing this may result in errors which the developers may choose not to address.",
                      category: "advanced"}
    }
}

task VirusInterpreter {
    input {
        String sampleId
        File purplePurityTsv
        File prupleQcFile
        File tumorSampleWgsMetricsFile
        File virusBreakendTsv
        File taxonomyDbTsv
        File virusReportingDbTsv
        String outputDir = "."

        String memory = "3GiB"
        String javaXmx = "2G"
        Int timeMinutes = 15
        String dockerImage = "quay.io/biowdl/virus-interpreter:1.2"
    }

    command {
        virus-interpreter -Xmx~{javaXmx} -XX:ParallelGCThreads=1  \
        -sample_id ~{sampleId} \
        -purple_purity_tsv ~{purplePurityTsv} \
        -purple_qc_file ~{prupleQcFile} \
        -tumor_sample_wgs_metrics_file ~{tumorSampleWgsMetricsFile} \
        -virus_breakend_tsv ~{virusBreakendTsv} \
        -taxonomy_db_tsv ~{taxonomyDbTsv} \
        -virus_reporting_db_tsv ~{virusReportingDbTsv} \
        -output_dir ~{outputDir}
    }

    output {
        File virusAnnotatedTsv = "~{outputDir}/~{sampleId}.virus.annotated.tsv"
    }

    runtime {
        time_minutes: timeMinutes # !UnknownRuntimeKey
        docker: dockerImage
        memory: memory
    }

    parameter_meta {
        sampleId: {description: "The name of the sample.", category: "required"}
        purplePurityTsv: {description: "The purity file produced by purple.", category: "required"}
        prupleQcFile: {description: "The QC file produced by purple.", category: "required"}
        tumorSampleWgsMetricsFile: {description: "The picard WGS metrics file for this sample.", category: "required"}
        virusBreakendTsv: {description: "The TSV output from virusbreakend.", category: "required"}
        taxonomyDbTsv: {description: "A taxonomy database tsv.", category: "required"}
        virusReportingDbTsv: {description: "A virus reporting tsv.", category: "required"}
        outputDir: {description: "The directory the output will be written to.", category: "required"}
        memory: {description: "The amount of memory this job will use.", category: "advanced"}
        javaXmx: {description: "The maximum memory available to the program. Should be lower than `memory` to accommodate JVM overhead.",
                  category: "advanced"}
        timeMinutes: {description: "The maximum amount of time the job will run in minutes.", category: "advanced"}
        dockerImage: {description: "The docker image used for this task. Changing this may result in errors which the developers may choose not to address.",
                      category: "advanced"}
    }
}