Medically relevant tandem repeats in nanopore sequencing of control cohorts

Research and diagnostics for medically relevant tandem repeats and repeat expansions are hampered by the lack of population-scale databases. We attempt to fill this gap using our pathSTR web tool, which leverages long-read sequencing of large cohorts to determine repeat length and sequence composition in the general population. The current version includes 878 individuals of the 1000 Genomes Project cohort sequenced on the Oxford Nanopore Technologies PromethION. A comprehensive set of medically relevant tandem repeats were genotyped using STRdust to determine the tandem repeat length and sequence composition. PathSTR provides rich visualizations of this dataset, as well as the feature to upload one's own data for comparison along the control cohort. We demonstrate the implementation of this application using data from targeted nanopore sequencing of a patient with Myotonic Dystrophy type 1. This resource will empower the genetics community to get a more complete overview of normal variation in tandem repeat length and sequence composition, and enable a better assessment of the pathogenic impact of tandem repeats observed in patients. PathSTR is available at https://pathstr.bioinf.be ### Competing Interest Statement WDC has received free consumables and travel reimbursement from Oxford Nanopore Technologies. ### Funding Statement WDC is a recipient of a postdoctoral fellowship from FWO [12ASR24N]. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study concerning the DM1 patient was approved by the Swedish Ethical Review Authority (2019-04746), and written informed consent was obtained from the participating individual or their respective legal guardians. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data generated in this project can be accessed at https://pathstr.bioinf.be, where the data can be queried, visualized, and downloaded in the form of a tab-separated file or individual VCF files as generated by STRdust. The original sequencing data is available at https://ftp.1000genomes.ebi.ac.uk/vol1/ftp/data\_collections/1KG\_ONT_VIENNA/hg38/