TelomereHunter2: Improved <i>In silico</i> Telomere Analysis Software for Precision Oncology and Single-cell Studies

Abstract Motivation Telomere biology plays a critical role in multiple biological processes including carcinogenesis, aging, and genome stability. With increasing availability of DNA-sequence datasets, telomere length and composition are more frequently directly inferred in silico. The TelomereHunter software is used in genome research and precision oncology to study telomere maintenance mechanisms from routine sequencing data. However, bioinformatics tools face constant challenges such as increasing the number and size of genomic datasets, novel file formats and deprecating software components. Results We developed TelomereHunter2 (TH2) to create a sustainable framework for telomere analysis. By containerizing our software and improving the runtime by up to 74%, we simplify the integration of TH2 into diverse precision oncology workflows and computational environments. We also extended TH2 to support non-human genomes and single-cell sequencing approaches, broadening its applications across species and methodologies. We demonstrate TH2 improvements on a pilot dataset. Availability and implementation TelomereHunter2 is an open-source Python package released under the GPL-3.0 license. It is distributed via PyPI and the source code, documentation, and wiki are available at: https://github.com/ferdinand-popp/TelomereHunter2.