excluderanges: exclusion sets for T2T-CHM13, GRCm39, and other genome assemblies

Exclusion regions are sections of reference genomes with abnormal pileups of short sequencing reads. Removing reads overlapping them improves biological signal, and these benefits are most pronounced in differential analysis settings. Several labs created exclusion region sets, available primarily through ENCODE and Github. However, the variety of exclusion sets creates uncertainty which sets to use. Furthermore, gap regions (e.g. centromeres, telomeres, short arms) create additional considerations in generating exclusion sets. We generated exclusion sets for the latest human T2T-CHM13 and mouse GRCm39 genomes and systematically assembled and annotated these and other sets in the excluderanges R/Bioconductor data package, also accessible via the BEDbase.org API. The package provides unified access to 82 GenomicRanges objects covering six organisms, multiple genome assemblies, and types of exclusion regions. For human hg38 genome assembly, we recommend hg38.Kundaje.GRCh38_unified_blacklist as the most well-curated and annotated, and sets generated by the Blacklist tool for other organisms.

Automated summary

Exclusion regions are abnormal sections of reference genomes where short sequencing reads pile up. Removing reads overlapping these regions improves biological signal, particularly in differential analysis. Multiple exclusion region sets have been created by labs, primarily available through ENCODE and Github, causing uncertainty in which sets to use. Additionally, gap regions like centromeres, telomeres, and short arms pose further considerations when generating exclusion sets.