adjust cnvkit/batch for germline mode

modules/cnvkit/batch/main.nf

@@ -28,34 +28,48 @@ process CNVKIT_BATCH {
     script:
     def args = task.ext.args ?: ''
 
-    // execute samtools only when cram files are input, cnvkit runs natively on bam but is prohibitively slow
+    def tumor_exists = tumor ? true : false
-    // input pair is assumed to have same extension if both exist
+    def normal_exists = normal ? true : false
-    def is_cram = tumor.Extension == "cram" ? true : false
+
-    def tumor_out = is_cram ? tumor.BaseName + ".bam" : "${tumor}"
+    // execute samtools only when cram files are input, cnvkit runs natively on bam but is prohibitively slow
+    def tumor_cram = tumor_exists && tumor.Extension == "cram" ? true : false
+    def normal_cram = normal_exists && normal.Extension == "cram" ? true : false
+
+    def tumor_out = tumor_cram ? tumor.BaseName + ".bam" : "${tumor}"
 
-    // do not run samtools on normal samples in tumor_only mode
-    def normal_exists = normal ? true: false
     // tumor_only mode does not need fasta & target
     // instead it requires a pre-computed reference.cnn which is built from fasta & target
     def (normal_out, normal_args, fasta_args) = ["", "", ""]
 
     if (normal_exists){
         def normal_prefix = normal.BaseName
-        normal_out = is_cram ? "${normal_prefix}" + ".bam" : "${normal}"
+        normal_out = normal_cram ? "${normal_prefix}" + ".bam" : "${normal}"
-        normal_args = normal_prefix ? "--normal $normal_out" : ""
         fasta_args = fasta ? "--fasta $fasta" : ""
+
+        // germline mode
+        // normal samples must be input without a flag
+        // requires flag --normal to be empty
+        if(!tumor_exists){
+            tumor_out = normal.BaseName + ".bam"
+            normal_args = "--normal "
+        }
+        // somatic mode
+        else {
+            normal_args = normal_prefix ? "--normal $normal_out" : ""
+        }
     }
 
     def target_args = targets ? "--targets $targets" : ""
     def reference_args = reference ? "--reference $reference" : ""
 
     """
-    if $is_cram; then
+    if $tumor_cram; then
         samtools view -T $fasta $tumor -@ $task.cpus -o $tumor_out
-        if $normal_exists; then
+    fi
+    if $normal_cram; then
         samtools view -T $fasta $normal -@ $task.cpus -o $normal_out
     fi
-    fi
+
 
     cnvkit.py \\
         batch \\

tests/config/test_data.config

@@ -23,6 +23,8 @@ params {
                 test_bed12                                     = "${test_data_dir}/genomics/sarscov2/genome/bed/test.bed12"
                 baits_bed                                      = "${test_data_dir}/genomics/sarscov2/genome/bed/baits.bed"
 
+                reference_cnn                                  = "${test_data_dir}/genomics/sarscov2/genome/cnn/reference.cnn"
+
                 kraken2                                        = "${test_data_dir}/genomics/sarscov2/genome/db/kraken2"
                 kraken2_tar_gz                                 = "${test_data_dir}/genomics/sarscov2/genome/db/kraken2.tar.gz"
 
@@ -145,6 +147,7 @@ params {
                 genome_21_multi_interval_bed_gz                = "${test_data_dir}/genomics/homo_sapiens/genome/chr21/sequence/multi_intervals.bed.gz"
                 genome_21_multi_interval_bed_gz_tbi            = "${test_data_dir}/genomics/homo_sapiens/genome/chr21/sequence/multi_intervals.bed.gz.tbi"
                 genome_21_chromosomes_dir                      = "${test_data_dir}/genomics/homo_sapiens/genome/chr21/sequence/chromosomes.tar.gz"
+                genome_21_reference_cnn                        = "${test_data_dir}/genomics/homo_sapiens/genome/chr21/sequence/reference_chr21.cnn"
 
                 dbsnp_146_hg38_elsites                         = "${test_data_dir}/genomics/homo_sapiens/genome/vcf/dbsnp_146.hg38.elsites"
                 dbsnp_146_hg38_vcf_gz                          = "${test_data_dir}/genomics/homo_sapiens/genome/vcf/dbsnp_146.hg38.vcf.gz"
@@ -414,9 +417,6 @@ params {
             'txt' {
                 hello                           = "${test_data_dir}/generic/txt/hello.txt"
             }
-            'cnn' {
-                reference                       = "${test_data_dir}/generic/cnn/reference.cnn"
-            }
             'cooler'{
                 test_pairix_pair_gz             = "${test_data_dir}/genomics/homo_sapiens/cooler/cload/hg19/hg19.GM12878-MboI.pairs.subsample.blksrt.txt.gz"
                 test_pairix_pair_gz_px2         = "${test_data_dir}/genomics/homo_sapiens/cooler/cload/hg19/hg19.GM12878-MboI.pairs.subsample.blksrt.txt.gz.px2"

tests/modules/cnvkit/batch/main.nf

@@ -5,6 +5,7 @@ nextflow.enable.dsl = 2
 include { CNVKIT_BATCH as CNVKIT_HYBRID    } from '../../../../modules/cnvkit/batch/main.nf'
 include { CNVKIT_BATCH as CNVKIT_WGS       } from '../../../../modules/cnvkit/batch/main.nf'
 include { CNVKIT_BATCH as CNVKIT_TUMORONLY } from '../../../../modules/cnvkit/batch/main.nf'
+include { CNVKIT_BATCH as CNVKIT_GERMLINE } from '../../../../modules/cnvkit/batch/main.nf'
 
 workflow test_cnvkit_hybrid {
 
@@ -47,10 +48,10 @@ workflow test_cnvkit_tumoronly {
 
     input = [
         [ id:'test'], // meta map
-        file(params.test_data['homo_sapiens']['illumina']['test2_paired_end_sorted_bam'], checkIfExists: true),
+        file(params.test_data['homo_sapiens']['illumina']['test2_paired_end_recalibrated_sorted_bam'], checkIfExists: true),
         []
     ]
-    reference = file(params.test_data['generic']['cnn']['reference'], checkIfExists: true)
+    reference = file(params.test_data['homo_sapiens']['genome']['genome_21_reference_cnn'], checkIfExists: true)
 
     CNVKIT_TUMORONLY ( input, [], [], reference )
 }
@@ -59,11 +60,24 @@ workflow test_cnvkit_tumoronly_cram {
 
     input = [
         [ id:'test'], // meta map
-        file(params.test_data['homo_sapiens']['illumina']['test2_paired_end_sorted_cram'], checkIfExists: true),
+        file(params.test_data['homo_sapiens']['illumina']['test2_paired_end_recalibrated_sorted_cram'], checkIfExists: true),
         []
     ]
     fasta     = file(params.test_data['homo_sapiens']['genome']['genome_fasta'], checkIfExists: true)
-    reference = file(params.test_data['generic']['cnn']['reference'], checkIfExists: true)
+    reference = file(params.test_data['homo_sapiens']['genome']['genome_21_reference_cnn'], checkIfExists: true)
 
     CNVKIT_TUMORONLY ( input, fasta, [], reference )
 }
+
+workflow test_cnvkit_germline_cram {
+
+    input = [
+        [ id:'test'], // meta map
+        [],
+        file(params.test_data['homo_sapiens']['illumina']['test2_paired_end_recalibrated_sorted_cram'], checkIfExists: true)
+    ]
+    fasta     = file(params.test_data['homo_sapiens']['genome']['genome_21_fasta'], checkIfExists: true)
+    targets = file(params.test_data['homo_sapiens']['genome']['genome_21_multi_interval_bed'], checkIfExists: true)
+
+    CNVKIT_GERMLINE ( input, fasta, targets,  [])
+}

tests/modules/cnvkit/batch/test.yml

@@ -92,9 +92,22 @@
     - cnvkit
     - cnvkit/batch
   files:
-    - path: output/cnvkit/reference.antitarget-tmp.bed
+    - path: output/cnvkit/reference_chr21.antitarget-tmp.bed
-    - path: output/cnvkit/reference.target-tmp.bed
+      md5sum: 3d4d20f9f23b39970865d29ef239d20b
-      md5sum: 26d25ff2d6c45b6d92169b3559c6acdb
+    - path: output/cnvkit/reference_chr21.target-tmp.bed
+      md5sum: 657b25dbda8516624efa8cb2cf3716ca
+    - path: output/cnvkit/test2.paired_end.recalibrated.sorted.antitargetcoverage.cnn
+      md5sum: 067115082c4af4b64d58c0dc3a3642e4
+    - path: output/cnvkit/test2.paired_end.recalibrated.sorted.bintest.cns
+      md5sum: f6adc75a0a86b7a921eca1b79a394cb0
+    - path: output/cnvkit/test2.paired_end.recalibrated.sorted.call.cns
+      md5sum: f7caeca04aba28b125ce26b511f42afb
+    - path: output/cnvkit/test2.paired_end.recalibrated.sorted.cnr
+      md5sum: d9bdb71ce807051369577ee7f807a40c
+    - path: output/cnvkit/test2.paired_end.recalibrated.sorted.cns
+      md5sum: 2b56aac606ba6183d018b30ca58afcec
+    - path: output/cnvkit/test2.paired_end.recalibrated.sorted.targetcoverage.cnn
+      md5sum: e6d0190c1c37ce6e41f76ca5b24ccca3
 
 - name: cnvkit batch test_cnvkit_tumoronly_cram
   command: nextflow run ./tests/modules/cnvkit/batch -entry test_cnvkit_tumoronly_cram -c ./tests/config/nextflow.config  -c ./tests/modules/cnvkit/batch/nextflow.config
@@ -102,6 +115,44 @@
     - cnvkit
     - cnvkit/batch
   files:
-    - path: output/cnvkit/reference.antitarget-tmp.bed
+    - path: output/cnvkit/reference_chr21.antitarget-tmp.bed
-    - path: output/cnvkit/reference.target-tmp.bed
+      md5sum: 3d4d20f9f23b39970865d29ef239d20b
-      md5sum: 26d25ff2d6c45b6d92169b3559c6acdb
+    - path: output/cnvkit/reference_chr21.target-tmp.bed
+      md5sum: 657b25dbda8516624efa8cb2cf3716ca
+    - path: output/cnvkit/test2.paired_end.recalibrated.sorted.antitargetcoverage.cnn
+      md5sum: 067115082c4af4b64d58c0dc3a3642e4
+    - path: output/cnvkit/test2.paired_end.recalibrated.sorted.bintest.cns
+      md5sum: f6adc75a0a86b7a921eca1b79a394cb0
+    - path: output/cnvkit/test2.paired_end.recalibrated.sorted.call.cns
+      md5sum: f7caeca04aba28b125ce26b511f42afb
+    - path: output/cnvkit/test2.paired_end.recalibrated.sorted.cnr
+      md5sum: d9bdb71ce807051369577ee7f807a40c
+    - path: output/cnvkit/test2.paired_end.recalibrated.sorted.cns
+      md5sum: 2b56aac606ba6183d018b30ca58afcec
+    - path: output/cnvkit/test2.paired_end.recalibrated.sorted.targetcoverage.cnn
+      md5sum: e6d0190c1c37ce6e41f76ca5b24ccca3
+
+- name: cnvkit batch test_cnvkit_germline_cram
+  command: nextflow run ./tests/modules/cnvkit/batch -entry test_cnvkit_germline_cram -c ./tests/config/nextflow.config  -c ./tests/modules/cnvkit/batch/nextflow.config
+  tags:
+    - cnvkit
+    - cnvkit/batch
+  files:
+    - path: output/cnvkit/multi_intervals.antitarget.bed
+      md5sum: 3d4d20f9f23b39970865d29ef239d20b
+    - path: output/cnvkit/multi_intervals.target.bed
+      md5sum: 86d30493bb2e619a93f4ebc2923d29f3
+    - path: output/cnvkit/reference.cnn
+      md5sum: a09ee4be5dda1cf0f68073bdb3aad8ec
+    - path: output/cnvkit/test2.paired_end.recalibrated.sorted.antitargetcoverage.cnn
+      md5sum: 067115082c4af4b64d58c0dc3a3642e4
+    - path: output/cnvkit/test2.paired_end.recalibrated.sorted.bintest.cns
+      md5sum: 68b62b75cd91b2ffe5633686fb943490
+    - path: output/cnvkit/test2.paired_end.recalibrated.sorted.call.cns
+      md5sum: df196edd72613c59186f4d87df3dc4a4
+    - path: output/cnvkit/test2.paired_end.recalibrated.sorted.cnr
+      md5sum: 3b4fc0cc73be78f978cfe2422470753e
+    - path: output/cnvkit/test2.paired_end.recalibrated.sorted.cns
+      md5sum: 4e67451dbcb6601fc3fa5dd7e570f1d4
+    - path: output/cnvkit/test2.paired_end.recalibrated.sorted.targetcoverage.cnn
+      md5sum: b4a49faf170e436ec32dcc21ccc3ce8f