Optional whitelist Severus calling (--severus_whitelist), patched Severus 1.7

CHANGELOG.md

@@ -7,6 +7,7 @@ and this project adheres to [Semantic Versioning](https://semver.org/spec/v2.0.0
 
 ### `Added`
 
+- [#215](https://github.com/IntGenomicsLab/lrsomatic/pull/215) - Added optional whitelist SV calling: `SEVERUS` now runs a patched Severus 1.7 image (`oras://docker.io/amberverhasselt/severus-sif:1.7-whitelist-6813dee`), whose output without a whitelist is identical to stock 1.7, and takes an optional whitelist BED: `--severus_whitelist <bed>` reports every SV inside the whitelisted regions, past the read-quality, minimum-support and VNTR filters, with corroboration required for single-read junctions. Extra flags go through `--severus_whitelist_args`. `--severus_whitelist` is not supported under Conda (@AmberVerhasselt).
 - [#197](https://github.com/IntGenomicsLab/lrsomatic/pull/197) - Added CHM13 support for ClairS-TO's Verdict module, which tags tumour-only calls as germline, somatic or subclonal somatic; its resources were GRCh38-only, so on CHM13 germline variants leaked into `somatic.vcf.gz`. With `--genome CHM13 --skip_ascat` the pipeline builds a CHM13 resource set from the ASCAT files it already downloads and passes it as `--cna_resource_dir`; a prepared directory can be given with `--clairsto_cna_resources` (validated at launch). Without `--skip_ascat` tagging comes from ASCAT's own tables instead (next entry) (@ljwharbers).
 - [#197](https://github.com/IntGenomicsLab/lrsomatic/pull/197) - Added `CLAIRSTO_VERDICT_TAG`: when ASCAT is in the run, Verdict's germline tagging is computed from ASCAT's purity, ploidy and segments instead of Verdict's own estimate, so `CLAIRSTO` runs with `--disable_verdict` and ASCAT runs before small variant calling. Output names are unchanged. The tables the tags were computed from are published as `<sample>_Tumor_Purity_Ploidy.txt` and `<sample>_Tumor_CNA.txt`, also on `--skip_ascat` runs (@ljwharbers).
 - [#197](https://github.com/IntGenomicsLab/lrsomatic/pull/197) - Added a stub nf-test for `TUMORONLY_SMALLVAR` covering both germline tagging paths (tag `small`) (@ljwharbers).

conf/modules.config

@@ -533,7 +533,7 @@ process {
 
     withName: '.*:SEVERUS' {
         ext.prefix = "."
-        ext.args = { "--min-support ${params.severus_minsupport} --output-read-ids " }
+        ext.args = { "--min-support ${params.severus_minsupport} --output-read-ids ${params.severus_whitelist ? (params.severus_whitelist_args ?: '') : ''}" }
         publishDir = [
             path: { "${params.outdir}/${meta.id}/variants/severus" },
             mode: params.publish_dir_mode,

docs/output.md

@@ -376,6 +376,8 @@ The germline/somatic split comes from a panel of normals and from ClairS-TO's Ve
 | `read_qual.txt`                           | file containing quality statistics about identified segements                     |
 | `severus.log`                             | log file                                                                          |
 
+With `--severus_whitelist` the same files are published here. Passing `--write-alignments` through `--severus_whitelist_args` adds a `read_alignments` file.
+
 #### `savana`
 
 SAVANA structural variant and copy-number calling. Runs alongside Severus/ASCAT rather than replacing

docs/usage.md

@@ -285,9 +285,13 @@ opt-in. See [VEP plugins](#vep-plugins) for sizes, licence terms and per-assembl
 
 #### SEVERUS Options
 
-| Parameter              | Description                                                                          |
-| ---------------------- | ------------------------------------------------------------------------------------ |
-| `--severus_minsupport` | Minimum number of supporting reads required for SEVERUS to call an SV. Default = `3` |
+| Parameter                  | Description                                                                                                                                                                          |
+| -------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ |
+| `--severus_minsupport`     | Minimum number of supporting reads required for SEVERUS to call an SV. Default = `3`                                                                                                 |
+| `--severus_whitelist`      | BED file of regions in which every SV is reported (Severus `--whitelist`). Passed to `SEVERUS` as `--whitelist`; its VCFs feed SV VEP, Wakhan and the report as usual. Default = off |
+| `--severus_whitelist_args` | Extra arguments for `SEVERUS`, only used with `--severus_whitelist`, e.g. `--whitelist-single-read any`, `--whitelist-allow-intra-region` or `--write-alignments`. Default = none    |
+
+`SEVERUS` runs a patched Severus 1.7 build ([AmberVerhasselt/Severus](https://github.com/AmberVerhasselt/Severus/tree/whitelist-reciprocal-corroboration)) from `oras://docker.io/amberverhasselt/severus-sif` (`docker.io/amberverhasselt/severus` under Docker); without `--severus_whitelist` its output is identical to stock Severus 1.7. Inside the whitelisted regions it skips the read-quality, minimum-support and VNTR filters, and keeps a junction supported by a single read only when a reciprocal or independently supported junction corroborates it. This is meant for loci such as the IG and TCR genes, where translocations are often carried by few, divergent reads. **`--severus_whitelist` is not supported under Conda**, which installs stock Severus.
 
 #### SAVANA Options