Camouflaged regions conceal critical regions in ATAC‐Seq and Hi‐C sequencing assays, hiding potential contributing factors in Alzheimer’s disease

For many regions of the genome, genetic variants are completely overlooked when using standard short‐read sequencing approaches because of either; (1) lack of coverage (i.e., ‘dark‐by‐depth'), or (2) reads aligning to multiple regions (i.e., ‘dark‐by‐MAPQ', a.k.a. ‘camouflaged’ genes). Multiple alignments occur because of genomic duplication events that contribute to molecular evolution, but present major analytical challenges for aligning short‐read sequencing data to the genome. We previously presented a method to identify and differentiate dark and camouflaged regions by analyzing the read depth and reads with multiple alignments. Here we present data demonstrating that not only do camouflaged regions conceal essential genetic variants, but they further conceal results from other short‐read sequencing assays, including ATAC‐Seq and Hi‐C. Our results have important implications for all disease research, including Alzheimer’s disease.