readVcf is Slow if ScanVcfParam which Regions is Lengthy

[DarioS]

Recently, U.S. Food and Drug Administration, National Institute of Standards and Technology and Illumina researchers defined highly reproducible regions (H.R.R.s) of the human genome and made available BED files to define a set of regions in which variant callers consistently call variants on technical replicate samples, effectively defining a while-list for whole genome sequencing data. readVcf takes a long time if which of ScanVcfParam is specified. Importing the V.C.F. takes about five minutes if which not specified but I terminated it after one hour when which was specified.

library(rtracklayer)
goldStandards <- list.files("HRR/", "bed", full.names = TRUE)
goldStandards <- lapply(goldStandards, import.bed)
goldStandards <- unlist(goldStandards)
goldStandards <- reduce(goldStandards)
> goldStandards
GRanges object with 2988875 ranges and 0 metadata columns:
    ...        ...
variants <- readVcf("DRAGENgermline.vcf.gz", param = ScanVcfParam(which = goldStandards)) # Stopped after one hour.

Importing the whole V.C.F. file into the session and then using subsetByOverlaps seems a reasonable and fast workaround. To best help other users, would a documentation change or code change be better to make this user experience nicer?

[vjcitn]

Interesting observation @DarioS . This topic (using the HRR resource) could merit a workflow package, which could then be referenced by VariantAnnotation documentation. Would you be up for this? A public VCF could be used to demonstrate the approach. Or a PR to the VariantAnnotation doc could be a rapid resolution of your concern. Did you consider breaking up goldStandards and performing the read on sorted, modest-sized, single-chromosome chunks?

[mtmorgan]

Does the filterVcf vignette address this use case?

[DarioS]

Indeed, Section 5.2 of filterVcf cignette recommends readVcf followed by findOverlaps. But Section 7 Appendix seems to advocate for using ScanVcfParam(which = theRegions). It's unclear which approach is better and for which scenarios.