update mrjd and hla

tools/dragen-germline/4.3.6/dragen-germline__4.3.6.cwl

@@ -79,6 +79,22 @@ requirements:
             exit 1
           fi
 
+          # DRAGEN Multi-region Joint Detection (MRJD) is a de novo germline small variant caller for paralogous regions.
+          # MRJD is compatible with the hg38, hg19 and GRCh37 reference genomes.
+          # https://help.dragen.illumina.com/product-guides/dragen-v4.3/dragen-dna-pipeline/small-variant-calling/multi-region-joint-detection
+          #
+          # Multi Region Joint Detection (MRJD) Caller should be runs as standalone pipeline on DRAGEN™ server (not in integrated with Germline Small VC)
+          # https://support.illumina.com/content/dam/illumina-support/documents/downloads/software/dragen/release-notes/200056923_00_DRAGEN_4_3_6_Customer-Release-Notes.pdf
+          echo "run MRJD" 1>&2
+          eval /opt/edico/bin/dragen \\
+              "--ref-dir=$(get_ref_path(inputs.reference_tar))" \\
+              "--bam-input=$(get_ref_path(inputs.bam_input))" \\
+              --enable-map-align=false \\
+              --enable-mrjd=true \\
+              --mrjd-enable-high-sensitivity-mode=true \\
+              "--output-directory=$(inputs.output_directory)" \\
+              "--output-file-prefix=$(inputs.output_file_prefix)"
+
           # Run dragen command and import options from cli
           "$(get_dragen_bin_path())" "\${@}"
       - |
@@ -747,7 +763,7 @@ inputs:
   enable_hla:
     label: enable hla
     doc: |
-      Enable HLA typing by setting --enable-hla flag to true
+      Enable HLA typing for class I genes by setting --enable-hla flag to true
     type: boolean?
     inputBinding:
       prefix: "--enable-hla="
@@ -756,7 +772,7 @@ inputs:
   hla_enable_class_2:
     label: hla enable class 2
     doc: |
-      Enable class II HLA typing by setting --hla-enable-class-2 flag to true
+      Enable HLA typing for class II genes by setting --hla-enable-class-2 flag to true
     type: boolean?
     inputBinding:
       prefix: "--hla-enable-class-2="
@@ -825,6 +841,28 @@ inputs:
     inputBinding:
       prefix: "--hla-min-reads="
       separate: False
+
+  # Multi-Region Joint Detection
+  enable_mrjd:
+    label: enable multi-region joint detection
+    doc: |
+      In DRAGEN v4.3, MRJD covers regions that include six clinically relevant genes: NEB, TTN, SMN1/2, PMS2, STRC, and IKBKG.
+      With this option enabled, the following two types of variants are reported: 1. Uniquely placed variants; 2. Region-ambiguous variants.
+    type: boolean?
+    inputBinding:
+      prefix: "--enable-mrjd="
+      separate: False
+  mrjd_enable_high_sensitivity_mode:
+    label: enable multi-region joint detection high sensitivity mode 
+    doc: |
+      In addition to 1. Uniquely placed variants and 2. Region-ambiguous variants, with this option enabled, 
+      the following two types of variants are reported: 3. Positions where the reference alleles in all paralogous regions are not the same; 
+      4. Variants that have been placed uniquely in one of the paralogous regions and no variant in the corresponding position in the other region
+    type: boolean?
+    inputBinding:
+      prefix: "--mrjd-enable-high-sensitivity-mode="
+      separate: False
+
   # Miscellaneous options
   lic_instance_id_location:
     label: license instance id location

tools/dragen-somatic/4.3.6/dragen-somatic__4.3.6.cwl

@@ -1159,15 +1159,6 @@ inputs:
       prefix: "--enable-cnv="
       separate: False
       valueFrom: "$(self.toString())"
-  enable_dux4_caller:
-    label: enable dux4
-    doc: |
-      Enable DUX4 CNV calling.
-    type: boolean?
-    inputBinding:
-      prefix: "--enable-dux4-caller="
-      separate: False
-      valueFrom: "$(self.toString())"
   cnv_normal_b_allele_vcf:
     label: cnv normal b allele vcf
     doc: |
@@ -1347,81 +1338,6 @@ inputs:
       prefix: "--tmb-db-threshold="
       separate: False
 
-  # HLA calling
-  # https://support-docs.illumina.com/SW/DRAGEN_v40/Content/SW/DRAGEN/HLACaller.htm
-  enable_hla:
-    label: enable hla
-    doc: |
-      Enable HLA typing by setting --enable-hla flag to true
-    type: boolean?
-    inputBinding:
-      prefix: "--enable-hla="
-      separate: False
-      valueFrom: "$(self.toString())"
-  hla_bed_file:
-    label: hla bed file
-    doc: |
-      Use the HLA region BED input file to specify the region to extract HLA reads from.
-      DRAGEN HLA Caller parses the input file for regions within the BED file, and then
-      extracts reads accordingly to align with the HLA allele reference.
-    type: File?
-    inputBinding:
-      prefix: "--hla-bed-file="
-      separate: False
-  hla_reference_file:
-    label: hla reference file
-    doc: |
-      Use the HLA allele reference file to specify the reference alleles to align against.
-      The input HLA reference file must be in FASTA format and contain the protein sequence separated into exons.
-      If --hla-reference-file is not specified, DRAGEN uses hla_classI_ref_freq.fasta from /opt/edico/config/.
-      The reference HLA sequences are obtained from the IMGT/HLA database.
-    type: File?
-    inputBinding:
-      prefix: "--hla-reference-file="
-      separate: False
-  hla_allele_frequency_file:
-    label: hla allele frequency file
-    doc: |
-      Use the population-level HLA allele frequency file to break ties if one or more HLA allele produces the same or similar results.
-      The input HLA allele frequency file must be in CSV format and contain the HLA alleles and the occurrence frequency in population.
-      If --hla-allele-frequency-file is not specified, DRAGEN automatically uses hla_classI_allele_frequency.csv from /opt/edico/config/.
-      Population-level allele frequencies can be obtained from the Allele Frequency Net database.
-    type: File?
-    inputBinding:
-      prefix: "--hla-allele-frequency-file="
-      separate: False
-  hla_tiebreaker_threshold:
-    label: hla tiebreaker threshold
-    doc: |
-      If more than one allele has a similar number of reads aligned and there is not a clear indicator for the best allele,
-      the alleles are considered as ties. The HLA Caller places the tied alleles into a candidate set for tie breaking based
-      on the population allele frequency. If an allele has more than the specified fraction of reads aligned (normalized to
-      the top hit), then the allele is included into the candidate set for tie breaking. The default value is 0.97.
-    type: float?
-    inputBinding:
-      prefix: "--hla-tiebreaker-threshold="
-      separate: False
-  hla_zygosity_threshold:
-    label: hla zygosity threshold
-    doc: |
-      If the minor allele at a given locus has fewer reads mapped than a fraction of the read count of the major allele,
-      then the HLA Caller infers homozygosity for the given HLA-I gene. You can use this option to specify the fraction value.
-      The default value is 0.15.
-    type: float?
-    inputBinding:
-      prefix: "--hla zygosity threshold="
-      separate: False
-  hla_min_reads:
-    label: hla min reads
-    doc: |
-      Set the minimum number of reads to align to HLA alleles to ensure sufficient coverage and perform HLA typing.
-      The default value is 1000 and suggested for WES samples. If using samples with less coverage, you can use a
-      lower threshold value.
-    type: int?
-    inputBinding:
-      prefix: "--hla-min-reads="
-      separate: False
-
   # RNA
   # https://support-docs.illumina.com/SW/DRAGEN_v40/Content/SW/DRAGEN/TPipelineIntro_fDG.htm
   enable_rna:

workflows/dragen-somatic-with-germline-pipeline/4.3.6/dragen-somatic-with-germline-pipeline__4.3.6.cwl

@@ -242,19 +242,14 @@ inputs:
   enable_cnv_germline:
     label: enable cnv germline
     doc: |
-      Enable CNV processing in the DRAGEN Host Software (somatic only)
+      Enable CNV processing in the DRAGEN Host Software (germline only)
     type: boolean?
   enable_cnv_somatic:
     label: enable cnv somatic
     doc: |
-      Enable CNV processing in the DRAGEN Host Software (germline only)
-    type: boolean?
-  enable_dux4_caller:
-    label: enable dux 4 caller
-    doc: |
-      Enable DUX4 fusion detection.
+      Enable CNV processing in the DRAGEN Host Software (somatic only)
     type: boolean?
-
+  
   # Phased / MNV Calling options
   vc_combine_phased_variants_distance_somatic:
     label: vc combine phased variants distance somatic
@@ -465,6 +460,7 @@ inputs:
     doc: |
       The -vc-enable-vcf-output option enables VCF file output during a gVCF run. The default value is false.
     type: boolean?
+
   # Downsampling options
   vc_max_reads_per_active_region:
     label: vc max reads per active region
@@ -478,6 +474,7 @@ inputs:
       specifies the maximum number of reads covering a given raw region.
       Default is 30000 for the somatic workflow
     type: int?
+
   # Ploidy support
   sample_sex:
     label: sample sex
@@ -489,6 +486,7 @@ inputs:
         symbols:
           - male
           - female
+
   # ROH options
   vc_enable_roh:
     label: vc enable roh
@@ -502,12 +500,14 @@ inputs:
       DRAGEN distributes blacklist files for all popular human genomes and automatically selects a blacklist to
       match the genome in use, unless this option is used explicitly select a file.
     type: File?
+
   # BAF options
   vc_enable_baf:
     label: vc enable baf
     doc: |
       Enable or disable B-allele frequency output. Enabled by default.
     type: boolean?
+
   # Somatic calling options
   vc_min_tumor_read_qual:
     label: vc min tumor read qual
@@ -573,6 +573,7 @@ inputs:
       The default is C/T,G/T, which correspond to OxoG and FFPE artifacts. Valid values include C/T, or G/T, or C/T,G/T,C/A.
       An artifact (or an artifact and its reverse compliment) cannot be listed twice.
       For example, C/T,G/A is not valid, because C->G and T->A are reverse compliments.
+
   # Post somatic calling filtering options
   # https://support-docs.illumina.com/SW/DRAGEN_v40/Content/SW/DRAGEN/PostSomaticFilters.htm
   vc_hard_filter:
@@ -815,12 +816,18 @@ inputs:
       from the TMB calculation. The default value is 10.
     type: int?
 
-  # HLA calling
+  # HLA calling only available to germline mode
   # https://support-docs.illumina.com/SW/DRAGEN_v40/Content/SW/DRAGEN/HLACaller.htm
+  # https://help.dragen.illumina.com/product-guides/dragen-v4.3/dragen-reference-support
   enable_hla:
     label: enable hla
     doc: |
-      Enable HLA typing by setting --enable-hla flag to true
+      Enable HLA typing for class I genes by setting --enable-hla flag to true
+    type: boolean?
+  hla_enable_class_2:
+    label: enable hla class 2
+    doc: |
+      Enable HLA typing for class II genes by setting --hla-enable-class-2 flag to true
     type: boolean?
   hla_bed_file:
     label: hla bed file
@@ -868,6 +875,23 @@ inputs:
       lower threshold value.
     type: int?
 
+  # Multi-Region Joint Detection only available to germline mode
+  # https://help.dragen.illumina.com/product-guides/dragen-v4.3/dragen-dna-pipeline/small-variant-calling/multi-region-joint-detection
+  # https://help.dragen.illumina.com/product-guides/dragen-v4.3/dragen-reference-support
+  enable_mrjd:
+    label: enable multi-region joint detection (mrjd)
+    doc: |
+      In DRAGEN v4.3, MRJD covers regions that include six clinically relevant genes: NEB, TTN, SMN1/2, PMS2, STRC, and IKBKG.
+      With this option enabled, the following two types of variants are reported: 1. Uniquely placed variants; 2. Region-ambiguous variants.
+    type: boolean?
+  mrjd_enable_high_sensitivity_mode:
+    label: enable multi-region joint detection high sensitivity mode
+    doc: |
+      In addition to 1. Uniquely placed variants and 2. Region-ambiguous variants, with this option enabled,
+      the following two types of variants are reported: 3. Positions where the reference alleles in all paralogous regions are not the same;
+      4. Variants that have been placed uniquely in one of the paralogous regions and no variant in the corresponding position in the other region
+    type: boolean?
+
   # RNA
   # https://support-docs.illumina.com/SW/DRAGEN_v40/Content/SW/DRAGEN/TPipelineIntro_fDG.htm
   enable_rna:
@@ -1082,9 +1106,11 @@ steps:
         source: qc_coverage_region_3
       qc_coverage_ignore_overlaps:
         source: qc_coverage_ignore_overlaps
-      #hla
+      #hla options
       enable_hla:
         source: enable_hla
+      hla_enable_class_2:
+        source: hla_enable_class_2
       hla_bed_file:
         source: hla_bed_file
       hla_reference_file:
@@ -1099,6 +1125,11 @@ steps:
         source: hla_min_reads
       lic_instance_id_location:
         source: lic_instance_id_location
+      #multi-region join detection options
+      enable_mrjd:
+        source: enable_mrjd
+      mrjd_enable_high_sensitivity_mode:
+        source: mrjd_enable_high_sensitivity_mode
     out:
       - id: dragen_germline_output_directory
       - id: dragen_bam_out
@@ -1191,8 +1222,6 @@ steps:
           ${
             return get_first_non_null_input(self);
           }
-      enable_dux4_caller:
-        source: enable_dux4_caller
       # Phased / MNV Calling Options
       # Phased / MNV Calling options
       vc_combine_phased_variants_distance:
@@ -1369,22 +1398,6 @@ steps:
         source: tmb_vaf_threshold
       tmb_db_threshold:
         source: tmb_db_threshold
-      # HLA calling
-      # https://support-docs.illumina.com/SW/DRAGEN_v40/Content/SW/DRAGEN/HLACaller.htm
-      enable_hla:
-        source: enable_hla
-      hla_bed_file:
-        source: hla_bed_file
-      hla_reference_file:
-        source: hla_reference_file
-      hla_allele_frequency_file:
-        source: hla_allele_frequency_file
-      hla_tiebreaker_threshold:
-        source: hla_tiebreaker_threshold
-      hla_zygosity_threshold:
-        source: hla_zygosity_threshold
-      hla_min_reads:
-        source: hla_min_reads
       # RNA
       # https://support-docs.illumina.com/SW/DRAGEN_v40/Content/SW/DRAGEN/TPipelineIntro_fDG.htm
       enable_rna: