Update: TNseq.wdl

README.md

 ### Variant Calling
-This APP developed for somatic short variant discovery (SNVs + Indels).
+This APP developed for germline and somatic short variant discovery (SNVs + Indels).
 
 ***Supported callers***
+> Germline
+* Haplotyper
+> Somatic
 * TNseq (TNhaplotyper2)
 * TNscope
 * VarScan

defaults

     "dbmills_dir": "oss://pgx-reference-data/GRCh38.d1.vd1/",
     "db_mills": "Mills_and_1000G_gold_standard.indels.hg38.vcf",
     "germline_resource": "oss://pgx-reference-data/gnomAD/af-only-gnomad.v3.1.1.vcf.gz",
+    "germline_resource_tbi": "oss://pgx-reference-data/gnomAD/af-only-gnomad.v3.1.1.vcf.gz.tbi",
     "sentieon_docker": "registry.cn-shanghai.aliyuncs.com/pgx-docker-registry/sentieon-genomics:v2020.10.07",
     "varscan_docker": "registry.cn-shanghai.aliyuncs.com/pgx-docker-registry/varscan2:v2.4.3",
     "annovar_docker": "registry.cn-shanghai.aliyuncs.com/pgx-docker-registry/annovar:v2018.04",
     "bcftools_docker": "registry.cn-shanghai.aliyuncs.com/pgx-docker-registry/bcftools:v1.9",
     "database": "oss://pgx-reference-data/annovar_hg38/",
     "regions": "oss://pgx-reference-data/bed/cbcga/S07604514_Covered.bed",
-    "set_pon": false,
-    "pon_vcf": "",
+    "tnseq_pon": "",
+    "tnscope_pon": "",
     "cosmic_vcf": "CosmicCodingMuts.hg38.v91.vcf",
     "cosmic_dir": "oss://pgx-reference-data/reference/cosmic/",
     "disk_size": "200",

inputs

   "{{ project_name }}.dbmills_dir": "{{ dbmills_dir }}",
   "{{ project_name }}.db_mills": "{{ db_mills }}",
   "{{ project_name }}.germline_resource": "{{ germline_resource }}",
+  "{{ project_name }}.germline_resource_tbi": "{{ germline_resource_tbi }}",
   "{{ project_name }}.sentieon_docker": "{{ sentieon_docker }}",
   "{{ project_name }}.varscan_docker": "{{ varscan_docker }}",
   "{{ project_name }}.annovar_docker": "{{ annovar_docker }}",
   "{{ project_name }}.maftools_docker": "{{ maftools_docker }}",
   "{{ project_name }}.database": "{{ database }}",
   "{{ project_name }}.regions": "{{ regions }}",
-  "{{ project_name }}.set_pon": {{ set_pon | tojson }},
-  "{{ project_name }}.pon_vcf": "{{ pon_vcf }}",
+  "{{ project_name }}.tnseq_pon": "{{ tnseq_pon }}",
+  "{{ project_name }}.tnscope_pon": "{{ tnscope_pon }}",
   "{{ project_name }}.cosmic_vcf": "{{ cosmic_vcf }}",
   "{{ project_name }}.cosmic_dir": "{{ cosmic_dir }}",
   "{{ project_name }}.disk_size": "{{ disk_size }}",

tasks/Dedup.wdl

 task Dedup {
 
-	String SENTIEON_INSTALL_DIR
-	String SENTIEON_LICENSE
-	String sample
-
-	File sorted_bam
-	File sorted_bam_index
-	String docker
-	String cluster_config
-	String disk_size
-
-
-	command <<<
-		set -o pipefail
-		set -e
-		export SENTIEON_LICENSE=${SENTIEON_LICENSE}
-		nt=$(nproc)
-		${SENTIEON_INSTALL_DIR}/bin/sentieon driver -t $nt -i ${sorted_bam} --algo LocusCollector --fun score_info ${sample}_score.txt
-		${SENTIEON_INSTALL_DIR}/bin/sentieon driver -t $nt -i ${sorted_bam} --algo Dedup --rmdup --score_info ${sample}_score.txt --metrics ${sample}_dedup_metrics.txt ${sample}.sorted.deduped.bam
-
-	>>>
-	
-	runtime {
-		docker: docker
-		cluster: cluster_config
-		systemDisk: "cloud_ssd 40"
-		dataDisk: "cloud_ssd " + disk_size + " /cromwell_root/"
-	}
-
-	output {
-		File score = "${sample}_score.txt"
-		File dedup_metrics = "${sample}_dedup_metrics.txt"
-		File Dedup_bam = "${sample}.sorted.deduped.bam"
-		File Dedup_bam_index = "${sample}.sorted.deduped.bam.bai"
-	}
+  String SENTIEON_INSTALL_DIR
+  String SENTIEON_LICENSE
+  String sample
+
+  File sorted_bam
+  File sorted_bam_index
+  String docker
+  String cluster_config
+  String disk_size
+
+  command <<<
+    set -o pipefail
+    set -e
+    export SENTIEON_LICENSE=${SENTIEON_LICENSE}
+    nt=$(nproc)
+    ${SENTIEON_INSTALL_DIR}/bin/sentieon driver -t $nt -i ${sorted_bam} --algo LocusCollector --fun score_info ${sample}_score.txt
+    ${SENTIEON_INSTALL_DIR}/bin/sentieon driver -t $nt -i ${sorted_bam} --algo Dedup --rmdup --score_info ${sample}_score.txt --metrics ${sample}_dedup_metrics.txt ${sample}.sorted.deduped.bam
+  >>>
+  
+  runtime {
+    docker: docker
+    cluster: cluster_config
+    systemDisk: "cloud_ssd 40"
+    dataDisk: "cloud_ssd " + disk_size + " /cromwell_root/"
+  }
+
+  output {
+    File score = "${sample}_score.txt"
+    File dedup_metrics = "${sample}_dedup_metrics.txt"
+    File Dedup_bam = "${sample}.sorted.deduped.bam"
+    File Dedup_bam_index = "${sample}.sorted.deduped.bam.bai"
+  }
 }
 
 

tasks/Haplotyper.wdl

 task Haplotyper {
-	
-	File ref_dir
-	File dbsnp_dir
-	
-	String SENTIEON_INSTALL_DIR
-	String SENTIEON_LICENSE
-	String fasta
-	File recaled_bam
-	File recaled_bam_index
-	File? regions
-	String dbsnp
-	String sample
-	String docker
-	String cluster_config
-	String disk_size
-
-	command <<<
-		set -o pipefail
-		set -e
-		export SENTIEON_LICENSE=${SENTIEON_LICENSE}
-		nt=$(nproc)
-		if [ ${regions} != "" ]; then
-			${SENTIEON_INSTALL_DIR}/bin/sentieon driver --interval ${regions} -r ${ref_dir}/${fasta} -t $nt -i ${recaled_bam} --algo Haplotyper -d ${dbsnp_dir}/${dbsnp} ${sample}_hc.vcf
-		else
-			${SENTIEON_INSTALL_DIR}/bin/sentieon driver -r ${ref_dir}/${fasta} -t $nt -i ${recaled_bam} --algo Haplotyper -d ${dbsnp_dir}/${dbsnp} ${sample}_hc.vcf
-		fi
-	>>>
-	
-	runtime {
-		docker: docker
-		cluster: cluster_config
-		systemDisk: "cloud_ssd 40"
-		dataDisk: "cloud_ssd " + disk_size + " /cromwell_root/"
-	}
-
-	output {
-		File vcf = "${sample}_hc.vcf"
-		File vcf_idx = "${sample}_hc.vcf.idx"
-	}
+  
+  File ref_dir
+  File dbsnp_dir
+  
+  String SENTIEON_INSTALL_DIR
+  String SENTIEON_LICENSE
+  String fasta
+  File recaled_bam
+  File recaled_bam_index
+  File recal_table
+  String dbsnp
+  String sample
+  String docker
+  String cluster_config
+  String disk_size
+
+  File? regions
+  Int? interval_padding
+
+  command <<<
+    set -o pipefail
+    set -e
+    export SENTIEON_LICENSE=${SENTIEON_LICENSE}
+    nt=$(nproc)
+
+    if [ ${regions} ]; then
+      INTERVAL="--interval ${regions} --interval_padding ${interval_padding}"
+    else
+      INTERVAL=""
+    fi
+
+    if [ ${pon_vcf} ]; then
+      PON="--pon ${pon_vcf}"
+      ${SENTIEON_INSTALL_DIR}/bin/sentieon util vcfindex ${pon_vcf}
+    else
+      PON=""
+    fi
+
+    ${SENTIEON_INSTALL_DIR}/bin/sentieon driver -t $nt \
+	--interval ${regions} -r ${ref_dir}/${fasta} \
+	-i ${recaled_bam} -q ${recal_table}\
+	--algo Haplotyper -d ${dbsnp_dir}/${dbsnp} \
+	${sample}_hc.vcf
+  >>>
+  
+  runtime {
+    docker: docker
+    cluster: cluster_config
+    systemDisk: "cloud_ssd 40"
+    dataDisk: "cloud_ssd " + disk_size + " /cromwell_root/"
+  }
+
+  output {
+    File vcf = "${sample}_hc.vcf"
+    File vcf_idx = "${sample}_hc.vcf.idx"
+  }
 }
 
 

tasks/Metrics.wdl

 task Metrics {
 
+  File ref_dir
+  String SENTIEON_INSTALL_DIR
+  String SENTIEON_LICENSE
+  String sample
+  String docker
+  String cluster_config
 
-	File ref_dir
-	String SENTIEON_INSTALL_DIR
-	String SENTIEON_LICENSE
-	String sample
-	String docker
-	String cluster_config
-
-	String fasta
-	File sorted_bam
-	File sorted_bam_index
-	String disk_size
-	
-
-
-	command <<<
-		set -o pipefail
-		set -e
-		export SENTIEON_LICENSE=${SENTIEON_LICENSE}
-		nt=$(nproc)
-		${SENTIEON_INSTALL_DIR}/bin/sentieon driver -r ${ref_dir}/${fasta} -t $nt -i ${sorted_bam} --algo MeanQualityByCycle ${sample}_mq_metrics.txt --algo QualDistribution ${sample}_qd_metrics.txt --algo GCBias --summary ${sample}_gc_summary.txt ${sample}_gc_metrics.txt --algo AlignmentStat ${sample}_aln_metrics.txt --algo InsertSizeMetricAlgo ${sample}_is_metrics.txt --algo CoverageMetrics --omit_base_output ${sample}_coverage_metrics
-
-		${SENTIEON_INSTALL_DIR}/bin/sentieon plot metrics -o ${sample}_metrics_report.pdf gc=${sample}_gc_metrics.txt qd=${sample}_qd_metrics.txt mq=${sample}_mq_metrics.txt isize=${sample}_is_metrics.txt
-	>>>
-	
-	runtime {
-		docker: docker
-		cluster: cluster_config
-		systemDisk: "cloud_ssd 40"
-		dataDisk: "cloud_ssd " + disk_size + " /cromwell_root/"
-	}
-	output {
-		File qd_metrics = "${sample}_qd_metrics.txt"
-		File qd_metrics_pdf = "${sample}_qd_metrics.pdf"
-		File mq_metrics = "${sample}_mq_metrics.txt"
-		File mq_metrics_pdf = "${sample}_mq_metrics.pdf"
-		File is_metrics = "${sample}_is_metrics.txt"
-		File is_metrics_pdf = "${sample}_is_metrics.pdf"
-		File gc_summary = "${sample}_gc_summary.txt"
-		File gc_metrics = "${sample}_gc_metrics.txt"
-		File gc_metrics_pdf = "${sample}_gc_metrics.pdf"
-		File aln_metrics = "${sample}_aln_metrics.txt"
-		File coverage_metrics_sample_summary = "${sample}_coverage_metrics.sample_summary"
-		File coverage_metrics_sample_statistics = "${sample}_coverage_metrics.sample_statistics"
-		File coverage_metrics_sample_interval_statistics = "${sample}_coverage_metrics.sample_interval_statistics"
-		File coverage_metrics_sample_cumulative_coverage_proportions = "${sample}_coverage_metrics.sample_cumulative_coverage_proportions"
-		File coverage_metrics_sample_cumulative_coverage_counts = "${sample}_coverage_metrics.sample_cumulative_coverage_counts"
-	}
+  String fasta
+  File sorted_bam
+  File sorted_bam_index
+  String disk_size
 
+  File? regions
+
+  command <<<
+    set -o pipefail
+    set -e
+    export SENTIEON_LICENSE=${SENTIEON_LICENSE}
+    nt=$(nproc)
+    
+    if [ ${regions} ]; then
+      INTERVAL="--interval ${regions}"
+    else
+      INTERVAL=""
+    fi
+    
+    ${SENTIEON_INSTALL_DIR}/bin/sentieon driver -t $nt \
+    -r ${ref_dir}/${fasta} $INTERVAL \
+    -i ${sorted_bam} \
+    --algo MeanQualityByCycle ${sample}_mq_metrics.txt \
+    --algo QualDistribution ${sample}_qd_metrics.txt \
+    --algo GCBias --summary ${sample}_gc_summary.txt ${sample}_gc_metrics.txt \
+    --algo AlignmentStat ${sample}_aln_metrics.txt \
+    --algo InsertSizeMetricAlgo ${sample}_is_metrics.txt \
+    --algo CoverageMetrics --omit_base_output ${sample}_coverage_metrics
+
+    ${SENTIEON_INSTALL_DIR}/bin/sentieon plot metrics -o ${sample}_metrics_report.pdf gc=${sample}_gc_metrics.txt qd=${sample}_qd_metrics.txt mq=${sample}_mq_metrics.txt isize=${sample}_is_metrics.txt
+  >>>
+  
+  runtime {
+    docker: docker
+    cluster: cluster_config
+    systemDisk: "cloud_ssd 40"
+    dataDisk: "cloud_ssd " + disk_size + " /cromwell_root/"
+  }
+  output {
+    File qd_metrics = "${sample}_qd_metrics.txt"
+    File qd_metrics_pdf = "${sample}_qd_metrics.pdf"
+    File mq_metrics = "${sample}_mq_metrics.txt"
+    File mq_metrics_pdf = "${sample}_mq_metrics.pdf"
+    File is_metrics = "${sample}_is_metrics.txt"
+    File is_metrics_pdf = "${sample}_is_metrics.pdf"
+    File gc_summary = "${sample}_gc_summary.txt"
+    File gc_metrics = "${sample}_gc_metrics.txt"
+    File gc_metrics_pdf = "${sample}_gc_metrics.pdf"
+    File aln_metrics = "${sample}_aln_metrics.txt"
+    File coverage_metrics_sample_summary = "${sample}_coverage_metrics.sample_summary"
+    File coverage_metrics_sample_statistics = "${sample}_coverage_metrics.sample_statistics"
+    File coverage_metrics_sample_interval_statistics = "${sample}_coverage_metrics.sample_interval_statistics"
+    File coverage_metrics_sample_cumulative_coverage_proportions = "${sample}_coverage_metrics.sample_cumulative_coverage_proportions"
+    File coverage_metrics_sample_cumulative_coverage_counts = "${sample}_coverage_metrics.sample_cumulative_coverage_counts"
+  }
 }
 
 

tasks/Realigner.wdl

 		set -e
 		export SENTIEON_LICENSE=${SENTIEON_LICENSE}
 		nt=$(nproc)
-		if [ ${regions} != "" ]; then
-			${SENTIEON_INSTALL_DIR}/bin/sentieon driver -r ${ref_dir}/${fasta} -t $nt -i ${Dedup_bam} --algo Realigner -k ${dbmills_dir}/${db_mills} --interval_list ${regions} ${sample}.sorted.deduped.realigned.bam
+		
+		if [ ${regions} ]; then
+		  INTERVAL="--interval_list ${regions}"
 		else
-			${SENTIEON_INSTALL_DIR}/bin/sentieon driver -r ${ref_dir}/${fasta} -t $nt -i ${Dedup_bam} --algo Realigner -k ${dbmills_dir}/${db_mills} ${sample}.sorted.deduped.realigned.bam
-		fi		
+		  INTERVAL=""
+		fi
+		
+		${SENTIEON_INSTALL_DIR}/bin/sentieon driver -t $nt \
+		-r ${ref_dir}/${fasta} $INTERVAL \
+		-i ${Dedup_bam} \
+		--algo Realigner -k ${dbmills_dir}/${db_mills} ${sample}.sorted.deduped.realigned.bam
+		
 	>>>
 
 	runtime {

tasks/TNscope.wdl

 task TNscope {
+  
+  String sample
+  String SENTIEON_INSTALL_DIR
+  String SENTIEON_LICENSE
+  File tumor_recaled_bam
+  File tumor_recaled_bam_index
+  File tumor_recal_table
+  File normal_recaled_bam
+  File normal_recaled_bam_index
+  File normal_recal_table
+  String tumor_name
+  String normal_name
 
+  File ref_dir
+  String fasta
+  File dbsnp_dir
+  String dbsnp
+  File? regions
+  Int? interval_padding
+  File? pon_vcf
 
-    String sample
-    String SENTIEON_INSTALL_DIR
-    String SENTIEON_LICENSE
-    File tumor_recaled_bam
-    File tumor_recaled_bam_index
-    File tumor_recal_table
-    File normal_recaled_bam
-    File normal_recaled_bam_index
-    File normal_recal_table
-    String tumor_name
-    String normal_name
+  String docker
+  String cluster_config	
+  String disk_size
 
-    File ref_dir
-    String fasta
-    File dbsnp_dir
-    String dbsnp
-    File? regions
-    
-    String docker
-    String cluster_config	
-    String disk_size
+  command <<<
+    set -o pipefail
+    set -e
+    export SENTIEON_LICENSE=${SENTIEON_LICENSE}
+    nt=$(nproc)
 
-    Boolean set_pon
-    File? pon_vcf
-    String pon_command = if set_pon then "--pon /cromwell_root/tmp/PON/$(basename ${pon_vcf})" else ""
-    
-    command <<<
-        set -o pipefail
-        set -e
-        export SENTIEON_LICENSE=${SENTIEON_LICENSE}
-        nt=$(nproc)
+    if [ ${regions} ]; then
+      INTERVAL="--interval ${regions} --interval_padding ${interval_padding}"
+    else
+      INTERVAL=""
+    fi
 
-        if ${set_pon}; then
-            mkdir -p /cromwell_root/tmp/PON/
-            cp ${pon_vcf} /cromwell_root/tmp/PON/
-            ${SENTIEON_INSTALL_DIR}/bin/sentieon util vcfindex /cromwell_root/tmp/PON/$(basename ${pon_vcf})
-        fi
-        
-        if [ ${regions} != "" ]; then
-            ${SENTIEON_INSTALL_DIR}/bin/sentieon driver -t $nt \
-            --interval ${regions} -r ${ref_dir}/${fasta} \
-            -i ${tumor_recaled_bam} -q ${tumor_recal_table} \
-            -i ${normal_recaled_bam} -q ${normal_recal_table} \
-            --algo TNscope \
-            --tumor_sample ${tumor_name} --normal_sample ${normal_name} \
-            --dbsnp ${dbsnp_dir}/${dbsnp} \
-            ${pon_command} \
-            ${sample}.TNscope.TN.vcf
-        else
-            ${SENTIEON_INSTALL_DIR}/bin/sentieon driver -t $nt \
-            -r ${ref_dir}/${fasta} \
-            -i ${tumor_recaled_bam} -q ${tumor_recal_table} \
-            -i ${normal_recaled_bam} -q ${normal_recal_table} \
-            --algo TNscope \
-            --tumor_sample ${tumor_name} --normal_sample ${normal_name} \
-            --dbsnp ${dbsnp_dir}/${dbsnp} \
-            ${pon_command} \
-            ${sample}.TNscope.TN.vcf		
-        fi
-    >>>
+    if [ ${pon_vcf} ]; then
+      PON="--pon ${pon_vcf}"
+      ${SENTIEON_INSTALL_DIR}/bin/sentieon util vcfindex ${pon_vcf}
+    else
+      PON=""
+    fi
+    
+    ${SENTIEON_INSTALL_DIR}/bin/sentieon driver -t $nt \
+    -r ${ref_dir}/${fasta} $INTERVAL \
+    -i ${tumor_recaled_bam} -q ${tumor_recal_table} \
+    -i ${normal_recaled_bam} -q ${normal_recal_table} \
+    --algo TNscope \
+    --tumor_sample ${tumor_name} --normal_sample ${normal_name} \
+    --dbsnp ${dbsnp_dir}/${dbsnp} \
+    $PON \
+    ${sample}.TNscope.TN.vcf
+  >>>
 
-    runtime {
-        docker: docker
-        cluster: cluster_config
-        systemDisk: "cloud_ssd 40"
-        dataDisk: "cloud_ssd " + disk_size + " /cromwell_root/"
-    }
+  runtime {
+    docker: docker
+    cluster: cluster_config
+    systemDisk: "cloud_ssd 40"
+    dataDisk: "cloud_ssd " + disk_size + " /cromwell_root/"
+  }
 
-    output {
-        File TNscope_vcf= "${sample}.TNscope.TN.vcf"
-        File TNscope_vcf_index = "${sample}.TNscope.TN.vcf.idx"
-    }
+  output {
+    File TNscope_vcf= "${sample}.TNscope.TN.vcf"
+    File TNscope_vcf_index = "${sample}.TNscope.TN.vcf.idx"
+  }
 
 }

tasks/TNseq.wdl

 task TNseq {
-	File ref_dir
-	File dbsnp_dir
-	String sample
-	String SENTIEON_INSTALL_DIR
-	String SENTIEON_LICENSE
-	String tumor_name
-	String normal_name
-	String docker
-	String cluster_config
 
-	String fasta
-	File germline_resource
-	File tumor_recaled_bam
-	File tumor_recaled_bam_index
-	File tumor_recal_table
-	File normal_recaled_bam
-	File normal_recaled_bam_index
-	File normal_recal_table
-	File TNseq_PoN
-	String dbsnp
-	String disk_size
-	File regions
+  String sample
+  String SENTIEON_INSTALL_DIR
+  String SENTIEON_LICENSE
+  File tumor_recaled_bam
+  File tumor_recaled_bam_index
+  File tumor_recal_table
+  File normal_recaled_bam
+  File normal_recaled_bam_index
+  File normal_recal_table
+  String tumor_name
+  String normal_name
 
-	command <<<
-		set -o pipefail
-		set -e
-		export SENTIEON_LICENSE=${SENTIEON_LICENSE}
-		nt=$(nproc)
+  File ref_dir
+  String fasta
+  File germline_resource
+  File germline_resource_tbi
+  File? regions
+  Int? interval_padding
+  File? pon_vcf
 
-		${SENTIEON_INSTALL_DIR}/bin/sentieon driver -t $nt --interval ${regions} -r ${ref_dir}/${fasta} -i ${corealigner_bam} --algo TNhaplotyper2 --tumor_sample ${tumor_name} --normal_sample ${normal_name} --dbsnp ${dbsnp_dir}/${dbsnp} ${sample}.TNseq.TN.vcf
+  String docker
+  String cluster_config  
+  String disk_size
 
+  command <<<
+    set -o pipefail
+    set -e
+    export SENTIEON_LICENSE=${SENTIEON_LICENSE}
+    nt=$(nproc)
 
-		${SENTIEON_INSTALL_DIR}/bin/sentieon driver -t $nt --interval ${regions} -r ${ref_dir}/${fasta} \
-		-i ${tumor_recaled_bam} -q ${tumor_recal_table} \
-		-i ${normal_recaled_bam} -q ${normal_recal_table} \
-		--algo TNseq --tumor_sample ${tumor_name} \
-		--normal_sample ${normal_name} \
-		--germline_vcf ${germline_resource} \
-		--pon ${TNseq_PoN} \
-		${sample}.TNseq.TN.tmp.vcf \
-		--algo OrientationBias --tumor_sample ${tumor_name} \
-		ORIENTATION_DATA \
-		--algo ContaminationModel --tumor_sample ${tumor_name} \
-		--normal_sample ${normal_name} \
-		--vcf ${germline_resource} \
-		--tumor_segments CONTAMINATION_DATA.segments \
-		CONTAMINATION_DATA
-		
-		sentieon driver -r REFERENCE \
-		--algo TNfilter --tumor_sample ${tumor_name} \
-		--normal_sample ${normal_name} \
-		-v ${sample}.TNseq.TN.tmp.vcf \
-		--contamination CONTAMINATION_DATA \
-		--tumor_segments CONTAMINATION_DATA.segments \
-		--orientation_priors ORIENTATION_DATA \
-		${sample}.TNseq.TN.vcf
-	>>>
+    if [ ${regions} ]; then
+      INTERVAL="--interval ${regions} --interval_padding ${interval_padding}"
+    else
+      INTERVAL=""
+    fi
 
-	runtime {
-		docker: docker
-		cluster: cluster_config
-		systemDisk: "cloud_ssd 40"
-		dataDisk: "cloud_ssd " + disk_size + " /cromwell_root/"
-	}
+    if [ ${pon_vcf} ]; then
+      PON="--pon ${pon_vcf}"
+      ${SENTIEON_INSTALL_DIR}/bin/sentieon util vcfindex ${pon_vcf}
+    else
+      PON=""
+    fi
 
-	output {
-		File TNseq_vcf= "${sample}.TNseq.TN.vcf"
-		File TNseq_vcf_index = "${sample}.TNseq.TN.vcf.idx"
-	}
+    ${SENTIEON_INSTALL_DIR}/bin/sentieon driver -t $nt \
+    -r ${ref_dir}/${fasta} $INTERVAL \
+    -i ${tumor_recaled_bam} -q ${tumor_recal_table} \
+    -i ${normal_recaled_bam} -q ${normal_recal_table} \
+    --algo TNhaplotyper2 \
+    --tumor_sample ${tumor_name} --normal_sample ${normal_name} \
+    --germline_vcf ${germline_resource} \
+    $PON \
+    ${sample}.TNseq.TN.tmp.vcf \
+    --algo OrientationBias --tumor_sample ${tumor_name} \
+    ${sample}.orientation \
+    --algo ContaminationModel \
+    --tumor_sample ${tumor_name} --normal_sample ${normal_name} \
+    --vcf ${germline_resource} \
+    --tumor_segments ${sample}.contamination.segments \
+    ${sample}.contamination
+    
+    sentieon driver -r REFERENCE \
+    --algo TNfilter \
+    --tumor_sample ${tumor_name} --normal_sample ${normal_name} \
+    -v ${sample}.TNseq.TN.tmp.vcf \
+    --contamination ${sample}.contamination \
+    --tumor_segments ${sample}.contamination.segments \
+    --orientation_priors ${sample}.orientation \
+    ${sample}.TNseq.TN.vcf
+  >>>
+
+  runtime {
+    docker: docker
+    cluster: cluster_config
+    systemDisk: "cloud_ssd 40"
+    dataDisk: "cloud_ssd " + disk_size + " /cromwell_root/"
+  }
+
+  output {
+    File TNseq_vcf = "${sample}.TNseq.TN.vcf"
+    File TNseq_vcf_index = "${sample}.TNseq.TN.vcf.idx"
+    File contamination = "${sample}.contamination"
+    File contamination_segments = "${sample}.contamination.segments"
+    File orientation = "${sample}.orientation"
+  }
 
 }

tasks/bcftools.wdl

-task bcftools {
-
-	Array[File] pon_vcf
-	String docker
-	String cluster_config
-	String disk_size
-	Boolean set_pon
-
-
-	command <<<
-		set -o pipefail
-		set -e
-		
-		if ${set_pon} ; then
-			mkdir -p /cromwell_root/tmp/bcftools/
-			for i in ${sep=" " pon_vcf}
-			do
-				bcftools view $i -Oz -o /cromwell_root/tmp/bcftools/$i.gz
-			done
-			
-			bcftools merge -m any -f PASS,. --force-samples /cromwell_root/tmp/bcftools/*.vcf.gz |\ 
-			bcftools plugin fill-AN-AC |\ 
-			bcftools filter -i 'SUM(AC)>1' > panel_of_normal.vcf
-		else
-			touch panel_of_normal.vcf
-		fi
-	>>>
-
-	runtime {
-		docker: docker
-		cluster: cluster_config
-		systemDisk: "cloud_ssd 40"
-		dataDisk: "cloud_ssd " + disk_size + " /cromwell_root/"
-	}
-	
-	output {
-		File panel_of_normal_vcf = "panel_of_normal.vcf"
-	}
-}

tasks/deduped_Metrics.wdl

 task deduped_Metrics {
-    
-    File ref_dir
-    String SENTIEON_INSTALL_DIR
-    String SENTIEON_LICENSE
-    String sample
-    String fasta
-    File Dedup_bam
-    File Dedup_bam_index
-    String docker
-    String cluster_config
-    String disk_size
 
+  File ref_dir
+  String SENTIEON_INSTALL_DIR
+  String SENTIEON_LICENSE
+  String sample
+  String fasta
+  File Dedup_bam
+  File Dedup_bam_index
+  String docker
+  String cluster_config
+  String disk_size
 
-    command <<<
-        set -o pipefail
-        set -e
-        export SENTIEON_LICENSE=${SENTIEON_LICENSE}
-        nt=$(nproc)
-        ${SENTIEON_INSTALL_DIR}/bin/sentieon driver -r ${ref_dir}/${fasta} -t $nt -i ${Dedup_bam} --algo CoverageMetrics --omit_base_output ${sample}_deduped_coverage_metrics --algo MeanQualityByCycle ${sample}_deduped_mq_metrics.txt --algo QualDistribution ${sample}_deduped_qd_metrics.txt --algo GCBias --summary ${sample}_deduped_gc_summary.txt ${sample}_deduped_gc_metrics.txt --algo AlignmentStat ${sample}_deduped_aln_metrics.txt --algo InsertSizeMetricAlgo ${sample}_deduped_is_metrics.txt --algo QualityYield ${sample}_deduped_QualityYield.txt --algo WgsMetricsAlgo ${sample}_deduped_WgsMetricsAlgo.txt
-    >>>
+  File? regions
 
-    runtime {
-        docker: docker
-        cluster: cluster_config
-        systemDisk: "cloud_ssd 40"
-        dataDisk: "cloud_ssd " + disk_size + " /cromwell_root/" 
-    }
+  command <<<
+    set -o pipefail
+    set -e
+    export SENTIEON_LICENSE=${SENTIEON_LICENSE}
+    nt=$(nproc)
 
-    output {
-        File deduped_coverage_metrics_sample_summary = "${sample}_deduped_coverage_metrics.sample_summary"
-        File deduped_coverage_metrics_sample_statistics = "${sample}_deduped_coverage_metrics.sample_statistics"
-        File deduped_coverage_metrics_sample_interval_statistics = "${sample}_deduped_coverage_metrics.sample_interval_statistics"
-        File deduped_coverage_metrics_sample_cumulative_coverage_proportions = "${sample}_deduped_coverage_metrics.sample_cumulative_coverage_proportions"
-        File deduped_coverage_metrics_sample_cumulative_coverage_counts = "${sample}_deduped_coverage_metrics.sample_cumulative_coverage_counts"
-        File deduped_mean_quality = "${sample}_deduped_mq_metrics.txt"
-        File deduped_qd_metrics = "${sample}_deduped_qd_metrics.txt"
-        File deduped_gc_summary = "${sample}_deduped_gc_summary.txt"
-        File deduped_gc_metrics = "${sample}_deduped_gc_metrics.txt"
-        File dedeuped_aln_metrics = "${sample}_deduped_aln_metrics.txt"
-        File deduped_is_metrics = "${sample}_deduped_is_metrics.txt"
-        File deduped_QualityYield = "${sample}_deduped_QualityYield.txt"
-        File deduped_wgsmetrics = "${sample}_deduped_WgsMetricsAlgo.txt"
-    }
+    if [ ${regions} ]; then
+      INTERVAL="--interval ${regions}"
+    else
+      INTERVAL=""
+    fi
+
+    ${SENTIEON_INSTALL_DIR}/bin/sentieon driver -t $nt \
+    -r ${ref_dir}/${fasta} $INTERVAL \
+    -i ${Dedup_bam} \
+    --algo CoverageMetrics --omit_base_output ${sample}_deduped_coverage_metrics \
+    --algo MeanQualityByCycle ${sample}_deduped_mq_metrics.txt \
+    --algo QualDistribution ${sample}_deduped_qd_metrics.txt \
+    --algo GCBias --summary ${sample}_deduped_gc_summary.txt ${sample}_deduped_gc_metrics.txt \
+    --algo AlignmentStat ${sample}_deduped_aln_metrics.txt \
+    --algo InsertSizeMetricAlgo ${sample}_deduped_is_metrics.txt \
+    --algo QualityYield ${sample}_deduped_QualityYield.txt \
+    --algo WgsMetricsAlgo ${sample}_deduped_WgsMetricsAlgo.txt
+  >>>
+
+  runtime {
+    docker: docker
+    cluster: cluster_config
+    systemDisk: "cloud_ssd 40"
+    dataDisk: "cloud_ssd " + disk_size + " /cromwell_root/" 
+  }
+
+  output {
+    File deduped_coverage_metrics_sample_summary = "${sample}_deduped_coverage_metrics.sample_summary"
+    File deduped_coverage_metrics_sample_statistics = "${sample}_deduped_coverage_metrics.sample_statistics"
+    File deduped_coverage_metrics_sample_interval_statistics = "${sample}_deduped_coverage_metrics.sample_interval_statistics"
+    File deduped_coverage_metrics_sample_cumulative_coverage_proportions = "${sample}_deduped_coverage_metrics.sample_cumulative_coverage_proportions"
+    File deduped_coverage_metrics_sample_cumulative_coverage_counts = "${sample}_deduped_coverage_metrics.sample_cumulative_coverage_counts"
+    File deduped_mean_quality = "${sample}_deduped_mq_metrics.txt"
+    File deduped_qd_metrics = "${sample}_deduped_qd_metrics.txt"
+    File deduped_gc_summary = "${sample}_deduped_gc_summary.txt"
+    File deduped_gc_metrics = "${sample}_deduped_gc_metrics.txt"
+    File dedeuped_aln_metrics = "${sample}_deduped_aln_metrics.txt"
+    File deduped_is_metrics = "${sample}_deduped_is_metrics.txt"
+    File deduped_QualityYield = "${sample}_deduped_QualityYield.txt"
+    File deduped_wgsmetrics = "${sample}_deduped_WgsMetricsAlgo.txt"
+  }
 }

tasks/mapping.wdl

 task mapping {
 
-	File ref_dir
-	String fasta
-	File fastq_1
-	File fastq_2
+  File ref_dir
+  String fasta
+  File fastq_1
+  File fastq_2
 
-	String SENTIEON_INSTALL_DIR
-	String SENTIEON_LICENSE
-	String group
-	String sample
-	String pl
-	String docker
-	String cluster_config
-	String disk_size
+  String SENTIEON_INSTALL_DIR
+  String SENTIEON_LICENSE
+  String group
+  String sample
+  String pl
+  String docker
+  String cluster_config
+  String disk_size
 
-	command <<<
-		set -o pipefail
-		set -e	
-		export SENTIEON_LICENSE=${SENTIEON_LICENSE}
-		nt=$(nproc)
-		${SENTIEON_INSTALL_DIR}/bin/bwa mem -M -R "@RG\tID:${group}\tSM:${sample}\tPL:${pl}" -t $nt -K 10000000 ${ref_dir}/${fasta} ${fastq_1} ${fastq_2} | ${SENTIEON_INSTALL_DIR}/bin/sentieon util sort -o ${sample}.sorted.bam -t $nt --sam2bam -i -
-	>>>
+  command <<<
+    set -o pipefail
+    set -e  
+    export SENTIEON_LICENSE=${SENTIEON_LICENSE}
+    nt=$(nproc)
+    ${SENTIEON_INSTALL_DIR}/bin/bwa mem -M -R "@RG\tID:${group}\tSM:${sample}\tPL:${pl}" -t $nt -K 10000000 ${ref_dir}/${fasta} ${fastq_1} ${fastq_2} | ${SENTIEON_INSTALL_DIR}/bin/sentieon util sort -o ${sample}.sorted.bam -t $nt --sam2bam -i -
+  >>>
 
-	runtime {
-		docker: docker
-		cluster: cluster_config
-		systemDisk: "cloud_ssd 40"
-		dataDisk: "cloud_ssd " + disk_size + " /cromwell_root/"
-	}
-	output {
-		File sorted_bam = "${sample}.sorted.bam"
-		File sorted_bam_index = "${sample}.sorted.bam.bai"
-	}
+  runtime {
+    docker: docker
+    cluster: cluster_config
+    systemDisk: "cloud_ssd 40"
+    dataDisk: "cloud_ssd " + disk_size + " /cromwell_root/"
+  }
+  output {
+    File sorted_bam = "${sample}.sorted.bam"
+    File sorted_bam_index = "${sample}.sorted.bam.bai"
+  }
 }

workflow.wdl

     File dbsnp_dir
     String dbsnp
     File germline_resource
+    File germline_resource_tbi
+    
     File? regions
+    Int? interval_padding
+
     File database
     String disk_size
     String cluster_config
 
-    Boolean set_pon
-    File? pon_vcf
+    File? tnseq_pon
+    File? tnscope_pon
     File? cosmic_dir
     String? cosmic_vcf
 
     Boolean tnseq
     Boolean tnscope
     Boolean varscan
-
-
+    
     call mapping.mapping as tumor_mapping {
         input: 
         group=sample_id + '_tumor',
         sorted_bam=normal_mapping.sorted_bam,
         sorted_bam_index=normal_mapping.sorted_bam_index,
         sample=sample_id + '_normal',
+        regions=regions,
         docker=sentieon_docker,
         disk_size=disk_size,
         cluster_config=cluster_config
         Dedup_bam=normal_Dedup.Dedup_bam,
         Dedup_bam_index=normal_Dedup.Dedup_bam_index,
         sample=sample_id + '_normal',
+        regions=regions,
         docker=sentieon_docker,
         disk_size=disk_size,
         cluster_config=cluster_config
             ref_dir=ref_dir,
             recaled_bam=normal_BQSR.recaled_bam,
             recaled_bam_index=normal_BQSR.recaled_bam_index,
+            recaled_table=normal_BQSR.recal_table,
             dbsnp=dbsnp,
             dbsnp_dir=dbsnp_dir,
             regions=regions,
             fasta=fasta,
             ref_dir=ref_dir,
             regions=regions,
-            dbsnp=dbsnp,
-            dbsnp_dir=dbsnp_dir,
-            set_pon=set_pon,
-            pon_vcf=pon_vcf,
+            interval_padding=interval_padding,
+            germline_resource=germline_resource,
+            germline_resource_tbi=germline_resource_tbi,
+            pon_vcf=tnseq_pon,
             docker=sentieon_docker,
             cluster_config=cluster_config,
             disk_size=disk_size
             input:
             SENTIEON_INSTALL_DIR=SENTIEON_INSTALL_DIR,
             SENTIEON_LICENSE=SENTIEON_LICENSE,
-            fasta=fasta,
-            ref_dir=ref_dir,
-            regions=regions,
+            sample=sample_id,
             normal_recaled_bam=normal_BQSR.recaled_bam,
             normal_recaled_bam_index=normal_BQSR.recaled_bam_index,
             normal_recal_table=normal_BQSR.recal_table,
             tumor_recaled_bam=tumor_BQSR.recaled_bam,
             tumor_recaled_bam_index=tumor_BQSR.recaled_bam_index,
             tumor_recal_table=tumor_BQSR.recal_table,
+            normal_name=sample_id + "_normal",
+            tumor_name=sample_id + "_tumor",
+            fasta=fasta,
+            ref_dir=ref_dir,
+            regions=regions,
+            interval_padding=interval_padding,
             dbsnp=dbsnp,
             dbsnp_dir=dbsnp_dir,
-            set_pon=set_pon,
-            pon_vcf=pon_vcf,
-            cosmic_vcf=cosmic_vcf,
-            cosmic_dir=cosmic_dir,
-            tumor_name=sample_id + "_tumor",
-            normal_name=sample_id + "_normal",
+            pon_vcf=tnscope_pon,
             docker=sentieon_docker,
-            sample=sample_id,
-            disk_size=disk_size,
-            cluster_config=cluster_config
+            cluster_config=cluster_config,
+            disk_size=disk_size
         }
         
         call annovar.annovar as TNscope_annovar {