STRavinsky STR database and PGTailor PGT tool demonstrate superiority of CHM13-T2T over hg38 and hg19 for STR-based applications

Abstract

Short-Tandem-Repeats (STRs) have long been studied for possible roles in biological phenomena, and are utilized in multiple applications such as forensics, evolutionary studies and pre-implantation-genetic-testing (PGT). The two reference genomes most used by clinicians and researchers are GRCh37/hg19 and GRCh38/hg38, both constructed using mainly short-read-sequencing (SRS) in which all-STR-containing-reads cannot be assembled to the reference genome. With the introduction of long-read-sequencing (LRS) methods and the generation of the CHM13 reference genome, also known as T2T, many previously unmapped STRs were finally localized within the human genome. We generated STRavinsky, a compact STR database for three reference genomes, including T2T. We proceeded to demonstrate the advantages of T2T over hg19 and hg38, identifying nearly double the number of STRs throughout all chromosomes. Through STRavinsky, providing a resolution down to a specific genomic coordinate, we demonstrated extreme propensity of TGGAA repeats in p arms of acrocentric chromosomes, substantially corroborating early molecular studies suggesting a possible role in formation of Robertsonian translocations. Moreover, we delineated unique propensity of TGGAA repeats specifically in chromosome 16q11.2 and in 9q12. Finally, we harness the superior capabilities of T2T and STRavinsky to generate PGTailor, a novel web application dramatically facilitating design of STR-based PGT tests in mere minutes.