Split vep plugins into vep cache and vep plugins

genomic-medicine-sweden · Aug 13, 2024 · fa34748 · fa34748
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Showing 11 changed files with 83 additions and 8 deletions.
diff --git a/CHANGELOG.md b/CHANGELOG.md
@@ -20,6 +20,7 @@ and this project adheres to [Semantic Versioning](https://semver.org/spec/v2.0.0
 - [#266](https://github.com/genomic-medicine-sweden/nallo/pull/266) - Added CADD to dynamically calculate indel CADD-scores
 - [#270](https://github.com/genomic-medicine-sweden/nallo/pull/270) - Added SNV phasing stats to MultiQC
 - [#271](https://github.com/genomic-medicine-sweden/nallo/pull/271) - Added a `--skip_aligned_read_qc` parameter to skip the qc aligned reads subworkflow
+- [#314](https://github.com/genomic-medicine-sweden/nallo/pull/314) - Added a `--vep_plugin_files` parameter to separate VEP plugins from cache
 
 ### `Changed`
 
@@ -89,6 +90,7 @@ and this project adheres to [Semantic Versioning](https://semver.org/spec/v2.0.0
 | `--split_fastq`    | `--parallel_alignments`    |
 | `--extra_gvcfs`    |                            |
 | `--extra_snfs`     |                            |
+|                    | `--vep_plugin_files`       |
 
 > [!NOTE]
 > Parameter has been updated if both old and new parameter information is present.

diff --git a/assets/vep_plugin_files_schema.json b/assets/vep_plugin_files_schema.json
@@ -0,0 +1,26 @@
+{
+    "$schema": "http://json-schema.org/draft-07/schema",
+    "$id": "https://raw.githubusercontent.com/genomic-medicine-sweden/nallo/master/assets/vep_plugin_files_schema.json",
+    "title": "Schema for VEP plugin files and their indices",
+    "description": "Schema for VEP plugin files and their indices",
+    "type": "array",
+    "items": {
+        "type": "object",
+        "properties": {
+            "vep_files": {
+                "type": "string",
+                "anyOf": [
+                    {
+                        "format": "file-path"
+                    },
+                    {
+                        "format": "directory-path"
+                    }
+                ],
+                "exists": true,
+                "description": "Path to vep plugin files and their indices"
+            }
+        },
+        "required": ["vep_files"]
+    }
+}
diff --git a/conf/modules/snv_annotation.config b/conf/modules/snv_annotation.config
@@ -39,10 +39,10 @@ process {
     withName: '.*:SNV_ANNOTATION:ENSEMBLVEP_VEP' {
         ext.prefix = { "${meta.id}_vep" }
         ext.args = { [
-            "--dir_plugins ${cache}/Plugins",
-            "--plugin LoFtool,${cache}/LoFtool_scores.txt",
-            "--plugin pLI,${cache}/pLI_values.txt",
-            "--plugin SpliceAI,snv=${cache}/spliceai_21_scores_raw_snv_-v1.3-.vcf.gz,indel=${cache}/spliceai_21_scores_raw_snv_-v1.3-.vcf.gz",
+            "--dir_plugins .",
+            "--plugin LoFtool,LoFtool_scores.txt",
+            "--plugin pLI,pLI_values.txt",
+            "--plugin SpliceAI,snv=spliceai_21_scores_raw_snv_-v1.3-.vcf.gz,indel=spliceai_21_scores_raw_snv_-v1.3-.vcf.gz",
             '--distance 5000',
             '--buffer_size 20000',
             '--format vcf --max_sv_size 248387328',

diff --git a/conf/test.config b/conf/test.config
@@ -40,8 +40,9 @@ params {
     variant_catalog = params.pipelines_testdata_base_path + 'nallo/reference/variant_catalog_grch38.json'
 
     // SNV Annotation
-    vep_cache = params.pipelines_testdata_base_path + 'nallo/reference/vep_cache_test_data.tar.gz'
-    snp_db    = params.pipelines_testdata_base_path + 'nallo/testdata/snp_dbs.csv'
+    vep_cache        = params.pipelines_testdata_base_path + 'nallo/reference/vep_cache_test_data.tar.gz'
+    vep_plugin_files = params.pipelines_testdata_base_path + 'nallo/reference/vep_plugin_files.csv'
+    snp_db           = params.pipelines_testdata_base_path + 'nallo/testdata/snp_dbs.csv'
 
     // Rank variants
     reduced_penetrance       = params.pipelines_testdata_base_path + 'nallo/reference/reduced_penetrance.tsv'

diff --git a/docs/usage.md b/docs/usage.md
@@ -112,6 +112,23 @@ Some workflows require additional files:
 - If running without `--skip_repeat_annotation`, download a json variant catalog, (e.g. [variant_catalog_grch38.json](https://github.com/Clinical-Genomics/stranger/raw/main/stranger/resources/variant_catalog_grch38.json)) matching your reference genome to supply with `--variant_catalog`.
 
 - If running without `--skip_snv_annotation`, download [VEP cache](https://ftp.ensembl.org/pub/release-110/variation/vep/homo_sapiens_vep_110_GRCh38.tar.gz) to supply with `--vep_cache` and prepare a samplesheet with annotation databases ([`echtvar encode`](https://github.com/brentp/echtvar)) to supply with `--snp_db`:
+- If running without `--skip_snv_annotation`, you will also need to download VEP plugin files to supply with `--vep_plugin_files` see [example](https://raw.githubusercontent.com/genomic-medicine-sweden/test-datasets/nallo/reference/vep_plugin_files.csv). PLI, LoFtool and SpliceAI are required.
+
+```
+vep_files
+https://raw.githubusercontent.com/genomic-medicine-sweden/test-datasets/nallo/reference/vep_plugins/SpliceAI.pm
+https://raw.githubusercontent.com/genomic-medicine-sweden/test-datasets/nallo/reference/vep_plugins/LoFtool.pm
+https://raw.githubusercontent.com/genomic-medicine-sweden/test-datasets/nallo/reference/vep_plugins/spliceai_21_scores_raw_snv_-v1.3-.vcf.gz
+https://raw.githubusercontent.com/genomic-medicine-sweden/test-datasets/nallo/reference/vep_plugins/dbNSFP.pm
+https://raw.githubusercontent.com/genomic-medicine-sweden/test-datasets/nallo/reference/vep_plugins/plugin_config.txt
+https://raw.githubusercontent.com/genomic-medicine-sweden/test-datasets/nallo/reference/vep_plugins/spliceai_21_scores_raw_indel_-v1.3-.vcf.gz.tbi
+https://raw.githubusercontent.com/genomic-medicine-sweden/test-datasets/nallo/reference/vep_plugins/spliceai_21_scores_raw_indel_-v1.3-.vcf.gz
+https://raw.githubusercontent.com/genomic-medicine-sweden/test-datasets/nallo/reference/vep_plugins/spliceai_21_scores_raw_snv_-v1.3-.vcf.gz.tbi
+https://raw.githubusercontent.com/genomic-medicine-sweden/test-datasets/nallo/reference/vep_plugins/pLI_values.txt
+https://raw.githubusercontent.com/genomic-medicine-sweden/test-datasets/nallo/reference/vep_plugins/pLI.pm
+https://raw.githubusercontent.com/genomic-medicine-sweden/test-datasets/nallo/reference/vep_plugins/MaxEntScan.pm
+https://raw.githubusercontent.com/genomic-medicine-sweden/test-datasets/nallo/reference/vep_plugins/LoFtool_scores.txt
+```
 
 ```
 sample,file
@@ -247,6 +264,7 @@ Different processes may need extra input files
 | `trgt_repeats`                     | BED-file for repeats to be genotyped                                                                                                                                                                                                                                      | `string`  |         |          |        |
 | `snp_db`                           | Extra echtvar-databases to annotate SNVs with                                                                                                                                                                                                                             | `string`  |         |          |        |
 | `vep_cache`                        | Path to directory of vep_cache                                                                                                                                                                                                                                            | `string`  |         |          |        |
+| `vep_plugin_files`                 | A csv file with paths to vep plugin files, pLI, LoFtool and SpliceAI is required.                                                                                                                                                                                         | `string`  |         |          |        |
 | `bed`                              | BED file with regions of interest                                                                                                                                                                                                                                         | `string`  |         |          |        |
 | `hificnv_xy`                       |                                                                                                                                                                                                                                                                           | `string`  |         |          |        |
 | `hificnv_xx`                       |                                                                                                                                                                                                                                                                           | `string`  |         |          |        |

diff --git a/nextflow.config b/nextflow.config
@@ -23,6 +23,7 @@ params {
     snp_db                     = null
     variant_consequences_snv   = null
     vep_cache                  = null
+    vep_plugin_files           = null
     hificnv_xy                 = null
     hificnv_xx                 = null
     hificnv_exclude            = null

diff --git a/nextflow_schema.json b/nextflow_schema.json
@@ -383,6 +383,12 @@
                     "default": 110,
                     "description": "VEP cache version"
                 },
+                "vep_plugin_files": {
+                    "type": "string",
+                    "mimetype": "text/csv",
+                    "description": "A csv file with paths to vep plugin files, pLI, LoFtool and SpliceAI is required.",
+                    "schema": "assets/vep_plugin_files_schema.json"
+                },
                 "deepvariant_model_type": {
                     "type": "string",
                     "default": "PACBIO",

diff --git a/subworkflows/local/snv_annotation/main.nf b/subworkflows/local/snv_annotation/main.nf
@@ -13,6 +13,7 @@ workflow SNV_ANNOTATION {
     ch_fai                // channel: [mandatory] [ val(meta), path(fai) ]
     ch_vep_cache          // channel: [mandatory] [ path(cache) ]
     val_vep_cache_version // string: [mandatory] default: 110
+    ch_vep_extra_files    // channel: [mandatory] [ path(files) ]
     val_annotate_cadd     // bool: [mandatory]
     ch_cadd_header        // channel: [mandatory] [ path(txt) ]
     ch_cadd_resources     // channel: [mandatory] [ path(annotation) ]
@@ -59,7 +60,7 @@ workflow SNV_ANNOTATION {
         val_vep_cache_version,
         ch_vep_cache,
         ch_fasta,
-        []
+        ch_vep_extra_files
     )
     ch_versions = ch_versions.mix(ENSEMBLVEP_VEP.out.versions)
 

diff --git a/subworkflows/local/utils_nfcore_nallo_pipeline/main.nf b/subworkflows/local/utils_nfcore_nallo_pipeline/main.nf
@@ -73,7 +73,7 @@ def workflowDependencies = [
 def fileDependencies = [
     mapping          : ["fasta", "somalier_sites"],
     assembly         : ["fasta", "dipcall_par"], // The assembly workflow should be split into two - assembly and variant calling (requires ref)
-    snv_annotation   : ["snp_db", "vep_cache", "reduced_penetrance", "score_config_snv", "variant_consequences_snv"],
+    snv_annotation   : ["snp_db", "vep_cache", "vep_plugin_files", "reduced_penetrance", "score_config_snv", "variant_consequences_snv"],
     cnv_calling      : ["hificnv_xy", "hificnv_xx", "hificnv_exclude"],
     repeat_calling   : ["trgt_repeats"],
     repeat_annotation: ["variant_catalog"],

diff --git a/tests/main.nf.test b/tests/main.nf.test
@@ -23,6 +23,7 @@ nextflow_pipeline {
                 trgt_repeats             = params.pipelines_testdata_base_path + 'nallo/reference/pathogenic_repeats.hg38.bed'
                 variant_catalog          = params.pipelines_testdata_base_path + 'nallo/reference/variant_catalog_grch38.json'
                 vep_cache                = params.pipelines_testdata_base_path + 'nallo/reference/vep_cache_test_data.tar.gz'
+                vep_plugin_files         = params.pipelines_testdata_base_path + 'nallo/reference/vep_plugin_files.csv'
                 snp_db                   = params.pipelines_testdata_base_path + 'nallo/testdata/snp_dbs.csv'
                 somalier_sites           = params.pipelines_testdata_base_path + 'nallo/reference/somalier_sites.vcf.gz'
                 reduced_penetrance       = params.pipelines_testdata_base_path + 'nallo/reference/reduced_penetrance.tsv'
@@ -155,6 +156,7 @@ nextflow_pipeline {
                 trgt_repeats             = params.pipelines_testdata_base_path + 'nallo/reference/pathogenic_repeats.hg38.bed'
                 variant_catalog          = params.pipelines_testdata_base_path + 'nallo/reference/variant_catalog_grch38.json'
                 vep_cache                = params.pipelines_testdata_base_path + 'nallo/reference/vep_cache_test_data.tar.gz'
+                vep_plugin_files         = params.pipelines_testdata_base_path + 'nallo/reference/vep_plugin_files.csv'
                 snp_db                   = params.pipelines_testdata_base_path + 'nallo/testdata/snp_dbs.csv'
                 somalier_sites           = params.pipelines_testdata_base_path + 'nallo/reference/somalier_sites.vcf.gz'
                 reduced_penetrance       = params.pipelines_testdata_base_path + 'nallo/reference/reduced_penetrance.tsv'

diff --git a/workflows/nallo.nf b/workflows/nallo.nf
@@ -91,6 +91,8 @@ workflow NALLO {
                                                                     : Channel.value([])
     ch_vep_cache_unprocessed    = params.vep_cache                  ? Channel.fromPath(params.vep_cache).map { it -> [ [ id:'vep_cache' ], it ] }.collect()
                                                                     : Channel.value([[],[]])
+    ch_vep_extra_files_unsplit  = params.vep_plugin_files           ? Channel.fromPath(params.vep_plugin_files).collect()
+                                                                    : ''
     ch_expected_xy_bed          = params.hificnv_xy                 ? Channel.fromPath(params.hificnv_xy).collect()
                                                                     : ''
     ch_expected_xx_bed          = params.hificnv_xx                 ? Channel.fromPath(params.hificnv_xx).collect()
@@ -121,6 +123,21 @@ workflow NALLO {
         .collect()
         .set { ch_pedfile }
 
+    // Read and store paths in the vep_plugin_files file
+    if (params.vep_plugin_files) {
+        ch_vep_extra_files_unsplit.splitCsv ( header:true )
+            .map { row ->
+                f = file(row.vep_files[0])
+                if(f.isFile() || f.isDirectory()){
+                    return [f]
+                } else {
+                    error("\nVep database file ${f} does not exist.")
+                }
+            }
+            .collect()
+            .set {ch_vep_extra_files}
+    }
+
     //
     // Convert BAM files to FASTQ and vice versa
     //
@@ -341,6 +358,7 @@ workflow NALLO {
                     fai.map { name, fai -> [ [ id: name ], fai ] },
                     ch_vep_cache,
                     params.vep_cache_version,
+                    ch_vep_extra_files,
                     (params.cadd_resources && params.cadd_prescored),
                     ch_cadd_header,
                     ch_cadd_resources,