fix: strand-aware PRECEDEID/FOLLOWID for intergenic variants (#55)#102
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fix: strand-aware PRECEDEID/FOLLOWID for intergenic variants (#55)#102jmg421 wants to merge 1 commit into
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…ants (Bioconductor#55) Previously, locateVariants() classified flanking genes into PRECEDEID and FOLLOWID based solely on genomic position (left/right of variant) without considering gene strand. This meant: - A '-' strand gene to the RIGHT of the variant was incorrectly placed in PRECEDEID (should be FOLLOWID, since the variant is downstream of that gene's TSS) - A '-' strand gene to the LEFT of the variant was incorrectly placed in FOLLOWID (should be PRECEDEID, since the variant is upstream of that gene's TSS) Fix: after finding genes in the upstream/downstream positional windows, partition them by strand and assign to the correct ID list: - PRECEDEID: '+' genes in downstream window + '-' genes in upstream window - FOLLOWID: '+' genes in upstream window + '-' genes in downstream window This matches Ensembl VEP's upstream_gene_variant / downstream_gene_variant classification. For genomes with all '+' or '*' strand annotations, the behavior is unchanged (backward compatible). Closes Bioconductor#55
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Summary
Fixes #55.
locateVariants()withIntergenicVariantsnow correctly classifies flanking genes into PRECEDEID and FOLLOWID based on gene strand, matching Ensembl VEP'supstream_gene_variant/downstream_gene_variantsemantics.Problem
As reported in #55, PRECEDEID and FOLLOWID were assigned based purely on genomic position (right/left of variant) without considering the gene's transcriptional orientation. This meant:
-strand gene to the RIGHT of the variant was placed in PRECEDEID, but the variant is actually downstream of that gene (should be FOLLOWID)-strand gene to the LEFT of the variant was placed in FOLLOWID, but the variant is actually upstream of that gene (should be PRECEDEID)The reporter confirmed this by comparing with Ensembl VEP output, which correctly accounts for strand.
Fix
After finding genes in the upstream/downstream positional windows, partition them by strand:
+strand genes in downstream window +-strand genes in upstream window+strand genes in upstream window +-strand genes in downstream windowFor genomes with all
+or*strand annotations, the behavior is identical to before (backward compatible). The fix usesignore.strand=TRUEfor the initial overlap finding to ensure genes on both strands are captured.Testing
Added
test_locateVariants_intergenic_strand_issue55with a synthetic 4-gene scenario (2 strands × 2 positions) verifying correct strand-aware classification.Agentic tooling disclosure
This PR was produced with the assistance of Kiro CLI (Amazon's AI coding agent). All changes were reviewed and verified by the author.