Table2_TRcaller: a novel tool for precise and ultrafast tandem repeat variant genotyping in massively parallel sequencing reads.XLSX

Calling tandem repeat (TR) variants from DNA sequences is of both theoretical and practical significance. Some bioinformatics tools have been developed for detecting or genotyping TRs. However, little study has been done to genotyping TR alleles from long-read sequencing data, and the accuracy of genotyping TR alleles from next-generation sequencing data still needs to be improved. Herein, a novel algorithm is described to retrieve TR regions from sequence alignment, and a software program TRcaller has been developed and integrated into a web portal to call TR alleles from both short- and long-read sequences, both whole genome and targeted sequences generated from multiple sequencing platforms. All TR alleles are genotyped as haplotypes and the robust alleles will be reported, even multiple alleles in a DNA mixture. TRcaller could provide substantially higher accuracy (>99% in 289 human individuals) in detecting TR alleles with magnitudes faster (e.g., ∼2 s for 300x human sequence data) than the mainstream software tools. The web portal preselected 119 TR loci from forensics, genealogy, and disease related TR loci. TRcaller is validated to be scalable in various applications, such as DNA forensics and disease diagnosis, which can be expanded into other fields like breeding programs. Availability: TRcaller is available at https://www.trcaller.com/SignIn.aspx.

从 DNA 序列中检测串联重复（TR）变异在理论及实践层面均具有重要意义。已开发出一些生物信息学工具用于检测或基因分型 TR。然而，对长读长测序数据中 TR 等位基因的分型研究尚显不足，且从下一代测序数据中分型 TR 等位基因的准确性仍有待提升。本研究中，描述了一种新颖的算法，用于从序列比对中检索 TR 区域，并开发了一套名为 TRcaller 的软件程序，并将其集成至网络门户，以便从短读长和长读长序列中，以及由多个测序平台生成的全基因组及靶向序列中调用 TR 等位基因。所有 TR 等位基因均以单倍型形式进行基因分型，且将报告稳健的等位基因，即使在 DNA 混合物中存在多个等位基因。与主流软件工具相比，TRcaller 在检测 TR 等位基因方面能显著提高准确性（在 289 名人类个体中超过 99%），且速度更快（例如，对 300 倍人类序列数据进行检测仅需约 2 秒）。网络门户已预先选择了 119 个与法医、家系和疾病相关的 TR 位点。经验证，TRcaller 可在各种应用中实现可扩展性，如 DNA 法医鉴定和疾病诊断，并可扩展至其他领域，例如育种计划。可获取性：TRcaller 可在 https://www.trcaller.com/SignIn.aspx 获取。