fix: DBS across codon boundary correctly classified as nonsense (#84)#96
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fix: DBS across codon boundary correctly classified as nonsense (#84)#96jmg421 wants to merge 3 commits into
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Convert \itemize blocks that used \item{label}{desc} syntax to \describe,
and replace empty \item{}{} labels in \describe blocks with the function
signature from the body, resolving all checkRd warnings in isSNV-methods,
PolyPhenDb-class, readVcf-methods, SIFTDb-class, summarizeVariants-methods,
VariantType-class, VCF-class, VcfFile-class, VCFHeader-class, VRanges-class,
and VRangesList-class Rd files.
Co-Authored-By: Claude Sonnet 4.6 <noreply@anthropic.com>
…onductor#84) A dinucleotide base substitution (DBS) spanning a codon boundary that produces a stop codon in one of the two affected amino acids (e.g. VARAA='P*') was misclassified as 'nonsynonymous' instead of 'nonsense'. Root cause: the nonsense check used `as.character(varAA) %in% "*"` which only matches when the entire VARAA string is '*'. For multi-codon DBS, VARAA is multi-character (e.g. 'P*') and the check fails. Fix: use `grepl("*", ..., fixed=TRUE)` to detect stop codons anywhere in the translated variant amino acid sequence. Any premature stop truncates the protein regardless of flanking residues. Fixes Bioconductor#84
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Summary
A dinucleotide base substitution (DBS) that spans a codon boundary and produces a stop codon in one of the two resulting amino acids was misclassified as
nonsynonymousinstead ofnonsense.Example from the issue:
GG→AAon the - strand producesVARAA='P*'(proline + stop), but was reported as nonsynonymous because the check only matched when VARAA was exactly'*'.Root Cause
Line 184 of
methods-predictCoding.R:%in% "*"requires the entire string to equal*. For a DBS spanning two codons,varAAis two characters (e.g.P*), so the check fails.Fix
grepldetects a stop codon anywhere in the translated variant sequence. Any premature stop truncates the protein — it doesn't matter what precedes it.Testing
Added
test_predictCoding_dbs_nonsenseverifying that:P*→ nonsense (stop after one residue)*→ nonsense (classic single-codon stop)PQ→ nonsynonymous (no stop)*L→ nonsense (stop at first position)Fixes #84