長鎖リードとSTRキットを用いた一塩基変異によるリードレベルのショートタンデムリピートジェノタイピング

Variation in short tandem repeats (STRs) is implicated in Mendelian disease and complex traits, but can be difficult to resolve with short-read genome sequencing. We present STRkit, a software package for genotyping STRs using long read sequencing (LRS) that uses proximate single-nucleotide variants to improve genotyping accuracy without a priori haplotype information. We show that STRkit has unique strengths versus other methods: it can use data from both major LRS technologies (Pacific Biosciences HiFi [PB] and Oxford Nanopore [ONT]) to output both allele- and read-level copy number and sequence, performs best in benchmarking with F1 scores of 0.9631 and 0.9544 with PB and ONT data respectively, achieves higher rates of Mendelian consistency than other genotyping tools, and is open source software. STRkit's features open up new possibilities for association testing, assessing patterns of STR inheritance, and better understanding the functional effects of these notable repeat elements.