Clinical Research bioRxiv (all subjects)

FIDDL: depth-matched negative controls distinguish genuine interspecific introgression from competitive-mapping artifact

FIDDLintrogressioncompetitive mappingbioinformatics

The study demonstrates that competitively mapping reads to a concatenated multi-species reference produces false-positive introgression signals through two distinct mechanisms with opposite phylogenetic-distance signatures. Standard nuclear assemblies omit the mitochondrion and 2-micron plasmid, leaving high-copy cytoplasmic reads that confound detection. FIDDL uses depth-matched negative controls to correct for these artifacts, enabling more reliable identification of true interspecific introgression events. This method addresses a key technical limitation in genomic analyses and could improve evolutionary and biomedical studies that rely on accurate introgression detection.

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