lobSTR: A Short Tandem Repeat Profiler for Personal Genomes

Abstract

Short tandem repeats (STRs) have a wide range of applications, including medical genetics, forensics, and genetic genealogy. High-throughput sequencing (HTS) has the potential to profile hundreds of thousands of STR loci. However, mainstream bioinformatics pipelines are inadequate for the task. These pipelines treat STR mapping as gapped alignment, which results in cumbersome processing times and a biased sampling of STR alleles. Here, we present lobSTR, a novel method for profiling STRs in personal genomes. lobSTR harnesses concepts from signal processing and statistical learning to avoid gapped alignment and to address the specific noise patterns in STR calling. The speed and reliability of lobSTR exceed the performance of current mainstream algorithms for STR profiling. We validated lobSTR's accuracy by measuring its consistency in calling STRs from whole-genome sequencing of two biological replicates from the same individual, by tracing Mendelian inheritance patterns in STR alleles in whole-genome sequencing of a HapMap trio, and by comparing lobSTR results to traditional molecular techniques. Encouraged by the speed and accuracy of lobSTR, we used the algorithm to conduct a comprehensive survey of STR variations in a deeply sequenced personal genome. We traced the mutation dynamics of close to 100,000 STR loci and observed more than 50,000 STR variations in a single genome. lobSTR's implementation is an end-to-end solution. The package accepts raw sequencing reads and provides the user with the genotyping results. It is written in C/C++, includes multi-threading capabilities, and is compatible with the BAM format.

MIPSTR: a method for multiplex genotyping of germline and somatic STR variation across many individuals

“…We observed ratios as close as 49.9/50.1 (761 tag-defined read groups/764) and as far as 36/74 (40/71) for the three ascertained duplicate loci across three Col-0 siblings. These results suggest that with sufficient coverage, MIPSTR can readily identify heterozygous and somatic STR variants, which have been largely inaccessible by previous analytical or empirical methods (Gymrek et al 2012;Guilmatre et al 2013;Highnam et al 2013;Duitama et al 2014;Willems et al 2014). …”

“…This size range encompasses the majority of STRs (Gymrek et al 2012), except those that have undergone extreme expansion as seen in some human diseases and for the intronic STR in the A. thaliana IIL1 gene (Gatchel and Zoghbi 2005;Sureshkumar et al 2009). These extreme expansions are not directly accessible with MIPSTR due to our inability to capture and sequence both flanking regions.…”

“…However, STR variation is typically excluded or misreported for genomes sequenced with short reads. Recently, several tools have been developed to estimate STR unit number from short read sequencing data (Gymrek et al 2012;Highnam et al 2013;Tae et al 2013). These tools rely on the use of STR-spanning reads with unique flanking regions to improve mappability and ascertain STR unit number.…”

Permanent Reencryption: How to Survive Generations of Cryptanalysts to Come

“…As a result, the costs of sequencing a human's DNA dropped below 1000 USD, and more and more genotypes are This work is partially supported by the Fonds National de la Recherche Luxembourg (FNR) through PEARL grant FNR/P14/8149128. 1 In fact we have selected genomic information for precisely this combination, but for the remainder of this paper and in hindsight of the workshop, please consider it as onyl one example of information with such properties and possibly not the best one. The interested reader is here directed to the transcript of the talk and the controversial discussion it triggered.…”

“…For example, Melissa Gymrek and colleagues [1] were able to re-identify 13.1% of the donors contributing to the 1000-genome project, even though their data was anonymized, and Backes et al [2] warned about the potential erosion of genomic privacy.…”