Gatkcnvcaller

CHANGELOG.md

@@ -7,6 +7,7 @@ and this project adheres to [Semantic Versioning](https://semver.org/spec/v2.0.0
 
 ### `Added`
 
+- Add GATK's cnv calling pipeline [#362](https://github.com/nf-core/raredisease/pull/362)
 - Add `public_aws_ecr` profile for using AWS ECR public gallery images [#360](https://github.com/nf-core/raredisease/pull/360)
 - GATK's ShiftFasta to generate all the files required for mitochondrial analysis [#354](https://github.com/nf-core/raredisease/pull/354)
 - Feature to calculate CADD scores for indels [#325](https://github.com/nf-core/raredisease/pull/325)

README.md

@@ -54,6 +54,8 @@ On release, automated continuous integration tests run the pipeline on a full-si
 
 - [Manta](https://github.com/Illumina/manta)
 - [TIDDIT's sv](https://github.com/SciLifeLab/TIDDIT)
+- Copy number variant calling:
+  - [GATK GermlineCNVCaller](https://github.com/broadinstitute/gatk)
 
 **5. Annotation - SNV:**
 
@@ -153,8 +155,6 @@ For further information or help, don't hesitate to get in touch on the [Slack `#
 
 ## Citations
 
-<!-- TODO nf-core: Add citation for pipeline after first release. Uncomment lines below and update Zenodo doi and badge at the top of this file. -->
-
 If you use nf-core/raredisease for your analysis, please cite it using the following doi: [10.5281/zenodo.7995798](https://doi.org/10.5281/zenodo.7995798)
 
 An extensive list of references for the tools used by the pipeline can be found in the [`CITATIONS.md`](CITATIONS.md) file.

conf/modules/call_sv_germlinecnvcaller.config

@@ -0,0 +1,39 @@
+/*
+~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
+    Config file for defining DSL2 per module options and publishing paths
+~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
+    Available keys to override module options:
+        ext.args            = Additional arguments appended to command in module.
+        ext.args2           = Second set of arguments appended to command in module (multi-tool modules).
+        ext.args3           = Third set of arguments appended to command in module (multi-tool modules).
+        ext.prefix          = File name prefix for output files.
+        ext.when            = Conditional clause
+----------------------------------------------------------------------------------------
+*/
+
+//
+// gcnvcaller calling options
+//
+
+process {
+
+    withName: ".*CALL_STRUCTURAL_VARIANTS:CALL_SV_GERMLINECNVCALLER.*" {
+        publishDir = [
+            enabled: false
+        ]
+        ext.when = !params.skip_cnv_calling
+    }
+
+    withName: ".*CALL_STRUCTURAL_VARIANTS:CALL_SV_GERMLINECNVCALLER:GATK4_COLLECTREADCOUNTS" {
+        ext.args = "--format TSV --interval-merging-rule OVERLAPPING_ONLY"
+    }
+
+    withName: ".*CALL_STRUCTURAL_VARIANTS:CALL_SV_GERMLINECNVCALLER:GATK4_DETERMINEGERMLINECONTIGPLOIDY" {
+        ext.prefix = { "${meta.id}_ploidy" }
+    }
+
+    withName: ".*CALL_STRUCTURAL_VARIANTS:CALL_SV_GERMLINECNVCALLER:GATK4_GERMLINECNVCALLER" {
+        ext.args = "--run-mode CASE"
+        ext.prefix = { "${meta.id}_${model.simpleName}" }
+    }
+}

conf/modules/prepare_references.config

@@ -117,4 +117,15 @@ process {
             enabled: false
         ]
     }
+
+    withName: '.*PREPARE_REFERENCES:GATK_PREPROCESS_WGS' {
+        ext.args =  { "--padding 0  --interval-merging-rule OVERLAPPING_ONLY --exclude-intervals ${params.mito_name}" }
+        ext.when = { params.analysis_type.equals("wgs") && !params.readcount_intervals }
+    }
+
+    withName: '.*PREPARE_REFERENCES:GATK_PREPROCESS_WES' {
+        ext.args   = { "--bin-length 0  --interval-merging-rule OVERLAPPING_ONLY --exclude-intervals ${params.mito_name}" }
+        ext.when = { params.analysis_type.equals("wes") && !params.readcount_intervals }
+    }
+
 }

conf/test.config

@@ -23,6 +23,9 @@ params {
     igenomes_ignore = true
     mito_name       = 'MT'
 
+    // analysis params
+    skip_cnv_calling = true
+
     // Input data
     input          = 'https://raw.githubusercontent.com/nf-core/test-datasets/raredisease/testdata/samplesheet_trio.csv'
 

conf/test_one_sample.config

@@ -23,6 +23,9 @@ params {
     igenomes_ignore = true
     mito_name       = 'MT'
 
+    // analysis params
+    skip_cnv_calling = true
+
     // Input data
     input          = 'https://raw.githubusercontent.com/nf-core/test-datasets/raredisease/testdata/samplesheet_single.csv'
 

docs/output.md

@@ -10,6 +10,8 @@ The directories listed below will be created in the results directory after the
 
 The pipeline is built using [Nextflow](https://www.nextflow.io/) and processes data using the following steps:
 
+#### GATK GermlineCNVCaller (CNV calling)
+
 - [Alignment](#alignment)
   - [Mapping](#mapping)
     - [Bwa-mem2](#bwa-mem2)
@@ -33,6 +35,7 @@ The pipeline is built using [Nextflow](https://www.nextflow.io/) and processes d
 - [Variant calling - SV](#variant-calling---sv)
   - [Manta](#manta)
   - [TIDDIT sv](#tiddit-sv)
+  - [GATK GermlineCNVCaller - CNV calling](#gatk-germlinecnvcaller---cnv-calling)
   - [SVDB merge](#svdb-merge)
 - [Variant calling - repeat expansions](#variant-calling---repeat-expansions)
   - [Expansion Hunter](#expansion-hunter)
@@ -252,9 +255,13 @@ The pipeline performs variant calling using [Sentieon DNAscope](https://support.
 
 [TIDDIT's sv](https://github.com/SciLifeLab/TIDDIT) is used to identify chromosomal rearrangements using sequencing data. TIDDIT identifies intra and inter-chromosomal translocations, deletions, tandem-duplications and inversions, using supplementary alignments as well as discordant pairs. TIDDIT searches for discordant reads and split reads (supplementary alignments). Output vcf files are treated as intermediates and are not placed in the output folder by default.
 
+#### GATK GermlineCNVCaller - CNV calling
+
+[GATK GermlineCNVCaller](https://github.com/broadinstitute/gatk) is used to identify copy number variants in germline samples given their read counts and a model describing a sample's ploidy. Output vcf files are treated as intermediates and are not placed in the output folder by default.
+
 #### SVDB merge
 
-[SVDB merge](https://github.com/J35P312/SVDB#merge) is used to merge the variant calls from both Manta and TIDDIT. Output files are published in the output folder.
+[SVDB merge](https://github.com/J35P312/SVDB#merge) is used to merge the variant calls from GATK's GermlineCNVCaller (only if skip_cnv_calling is set to false), Manta, and TIDDIT. Output files are published in the output folder.
 
 <details markdown="1">
 <summary>Output files</summary>

docs/usage.md

@@ -17,9 +17,10 @@ Table of contents:
       - [3. Repeat expansions](#3-repeat-expansions)
       - [4. Variant calling - SNV](#4-variant-calling---snv)
       - [5. Variant calling - Structural variants](#5-variant-calling---structural-variants)
-      - [6. SNV annotation & Ranking](#6-snv-annotation--ranking)
-      - [7. SV annotation & Ranking](#7-sv-annotation--ranking)
-      - [8. Mitochondrial analysis](#8-mitochondrial-analysis)
+      - [6. Copy number variant calling](#6-copy-number-variant-calling)
+      - [7. SNV annotation & Ranking](#7-snv-annotation--ranking)
+      - [8. SV annotation & Ranking](#8-sv-annotation--ranking)
+      - [9. Mitochondrial analysis](#9-mitochondrial-analysis)
     - [Run the pipeline](#run-the-pipeline)
       - [Direct input in CLI](#direct-input-in-cli)
       - [Import from a config file (recommended)](#import-from-a-config-file-recommended)
@@ -188,7 +189,18 @@ The mandatory and optional parameters for each category are tabulated below.
 |           | target_bed |
 |           | bwa        |
 
-##### 6. SNV annotation & Ranking
+##### 6. Copy number variant calling
+
+| Mandatory                      | Optional                        |
+| ------------------------------ | ------------------------------- |
+| ploidy_model<sup>1</sup>       | readcount_intervals<sup>3</sup> |
+| gcnvcaller_model<sup>1,2</sup> |                                 |
+
+<sup>1</sup> Output from steps 3 & 4 of GATK's CNV calling pipeline run in cohort mode as described [here](https://gatk.broadinstitute.org/hc/en-us/articles/360035531152--How-to-Call-common-and-rare-germline-copy-number-variants).<br />
+<sup>2</sup> Sample file can be found [here](https://raw.githubusercontent.com/nf-core/test-datasets/raredisease/reference/gcnvmodels.tsv) (Note the header 'models' in the sample file).<br />
+<sup>3</sup> Output from step 1 of GATK's CNV calling pipeline as described [here](https://gatk.broadinstitute.org/hc/en-us/articles/360035531152--How-to-Call-common-and-rare-germline-copy-number-variants).<br />
+
+##### 7. SNV annotation & Ranking
 
 | Mandatory                     | Optional                       |
 | ----------------------------- | ------------------------------ |
@@ -215,7 +227,7 @@ no header and the following columns: `CHROM POS REF_ALLELE ALT_ALLELE AF`. Sampl
 
 > NB: We use CADD only to annotate small indels. To annotate SNVs with precomputed CADD scores, pass the file containing CADD scores as a resource to vcfanno instead. Files containing the precomputed CADD scores for SNVs can be downloaded from [here](https://cadd.gs.washington.edu/download) (description: "All possible SNVs of GRCh3<7/8>/hg3<7/8>")
 
-##### 7. SV annotation & Ranking
+##### 8. SV annotation & Ranking
 
 | Mandatory                  | Optional           |
 | -------------------------- | ------------------ |
@@ -227,7 +239,7 @@ no header and the following columns: `CHROM POS REF_ALLELE ALT_ALLELE AF`. Sampl
 
 <sup>1</sup> A CSV file that describes the databases (VCFs) used by SVDB for annotating structural variants. Sample file [here](https://github.com/nf-core/test-datasets/blob/raredisease/reference/svdb_querydb_files.csv). Information about the column headers can be found [here](https://github.com/J35P312/SVDB#Query).
 
-##### 8. Mitochondrial analysis
+##### 9. Mitochondrial analysis
 
 | Mandatory         | Optional |
 | ----------------- | -------- |

main.nf

@@ -23,6 +23,10 @@ params.bwa                            = WorkflowMain.getGenomeAttribute(params,
 params.bwamem2                        = WorkflowMain.getGenomeAttribute(params, 'bwamem2')
 params.call_interval                  = WorkflowMain.getGenomeAttribute(params, 'call_interval')
 params.cadd_resources                 = WorkflowMain.getGenomeAttribute(params, 'cadd_resources')
+params.gcnvcaller_model               = WorkflowMain.getGenomeAttribute(params, 'gcnvcaller_model')
+params.gens_interval_list             = WorkflowMain.getGenomeAttribute(params, 'gens_interval_list')
+params.gens_pon                       = WorkflowMain.getGenomeAttribute(params, 'gens_pon')
+params.gens_gnomad_pos                = WorkflowMain.getGenomeAttribute(params, 'gens_gnomad_pos')
 params.gnomad_af                      = WorkflowMain.getGenomeAttribute(params, 'gnomad_af')
 params.gnomad_af_idx                  = WorkflowMain.getGenomeAttribute(params, 'gnomad_af_idx')
 params.intervals_wgs                  = WorkflowMain.getGenomeAttribute(params, 'intervals_wgs')
@@ -33,22 +37,21 @@ params.known_indels                   = WorkflowMain.getGenomeAttribute(params,
 params.known_mills                    = WorkflowMain.getGenomeAttribute(params, 'known_mills')
 params.ml_model                       = WorkflowMain.getGenomeAttribute(params, 'ml_model')
 params.mt_fasta                       = WorkflowMain.getGenomeAttribute(params, 'mt_fasta')
+params.ploidy_model                   = WorkflowMain.getGenomeAttribute(params, 'ploidy_model')
 params.reduced_penetrance             = WorkflowMain.getGenomeAttribute(params, 'reduced_penetrance')
+params.readcount_intervals            = WorkflowMain.getGenomeAttribute(params, 'readcount_intervals')
 params.sequence_dictionary            = WorkflowMain.getGenomeAttribute(params, 'sequence_dictionary')
 params.score_config_snv               = WorkflowMain.getGenomeAttribute(params, 'score_config_snv')
 params.score_config_sv                = WorkflowMain.getGenomeAttribute(params, 'score_config_sv')
-params.target_bed                     = WorkflowMain.getGenomeAttribute(params, 'target_bed')
 params.svdb_query_dbs                 = WorkflowMain.getGenomeAttribute(params, 'svdb_query_dbs')
+params.target_bed                     = WorkflowMain.getGenomeAttribute(params, 'target_bed')
 params.variant_catalog                = WorkflowMain.getGenomeAttribute(params, 'variant_catalog')
 params.vep_filters                    = WorkflowMain.getGenomeAttribute(params, 'vep_filters')
 params.vcfanno_resources              = WorkflowMain.getGenomeAttribute(params, 'vcfanno_resources')
 params.vcfanno_toml                   = WorkflowMain.getGenomeAttribute(params, 'vcfanno_toml')
 params.vcfanno_lua                    = WorkflowMain.getGenomeAttribute(params, 'vcfanno_lua')
 params.vep_cache                      = WorkflowMain.getGenomeAttribute(params, 'vep_cache')
 params.vep_cache_version              = WorkflowMain.getGenomeAttribute(params, 'vep_cache_version')
-params.gens_interval_list             = WorkflowMain.getGenomeAttribute(params, 'gens_interval_list')
-params.gens_pon                       = WorkflowMain.getGenomeAttribute(params, 'gens_pon')
-params.gens_gnomad_pos                = WorkflowMain.getGenomeAttribute(params, 'gens_gnomad_pos')
 
 /*
 ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

modules.json

@@ -105,16 +105,31 @@
                         "git_sha": "2df2a11d5b12f2a73bca74f103691bc35d83c5fd",
                         "installed_by": ["modules"]
                     },
+                    "gatk4/collectreadcounts": {
+                        "branch": "master",
+                        "git_sha": "d25bf48327e86a7f737047a57ec264b90e22ce3d",
+                        "installed_by": ["modules"]
+                    },
                     "gatk4/createsequencedictionary": {
                         "branch": "master",
                         "git_sha": "541811d779026c5d395925895fa5ed35e7216cc0",
                         "installed_by": ["modules"]
                     },
+                    "gatk4/determinegermlinecontigploidy": {
+                        "branch": "master",
+                        "git_sha": "d25bf48327e86a7f737047a57ec264b90e22ce3d",
+                        "installed_by": ["modules"]
+                    },
                     "gatk4/filtermutectcalls": {
                         "branch": "master",
                         "git_sha": "2df2a11d5b12f2a73bca74f103691bc35d83c5fd",
                         "installed_by": ["modules"]
                     },
+                    "gatk4/germlinecnvcaller": {
+                        "branch": "master",
+                        "git_sha": "f6b848c6e1af9a9ecf4975aa8c8edad05e75e784",
+                        "installed_by": ["modules"]
+                    },
                     "gatk4/intervallisttools": {
                         "branch": "master",
                         "git_sha": "911696ea0b62df80e900ef244d7867d177971f73",
@@ -135,6 +150,16 @@
                         "git_sha": "2df2a11d5b12f2a73bca74f103691bc35d83c5fd",
                         "installed_by": ["modules"]
                     },
+                    "gatk4/postprocessgermlinecnvcalls": {
+                        "branch": "master",
+                        "git_sha": "39ca55cc30514169f8420162bafe4ecf673f4b9a",
+                        "installed_by": ["modules"]
+                    },
+                    "gatk4/preprocessintervals": {
+                        "branch": "master",
+                        "git_sha": "1226419498a14d17f98d12d6488d333b0dbd0418",
+                        "installed_by": ["modules"]
+                    },
                     "gatk4/printreads": {
                         "branch": "master",
                         "git_sha": "541811d779026c5d395925895fa5ed35e7216cc0",