TelOMpy enables single-molecule resolution of telomere length from optical genome mapping data

Abstract

The existing methods for assessing telomere length are limited in various ways, including resolution, scope, throughput, and reproducibility. These limitations stem from the applicability of laborious and complicated indirect approaches. We developed TelOMpy, a bioinformatics tool for determining the lengths of individual telomeres from optical genome mapping data. TelOMpy directly measures the absolute lengths of thousands of telomeres within a single sample, eliminating errors associated with indirect methodologies and ensuring high analytical power and reproducibility of results. We used optical genome mapping data generated from mice in a high-fat diet experiment to demonstrate the power of TelOMpy performance at the single-molecule level. Moreover, using our newly developed protocol for high-molecular-weight DNA extraction, we produced the first optical genome maps from sperm and compared telomere lengths between sperm and somatic tissue in overweight mice. TelOMpy reveals immense variation in the length of individual telomeres and the effect of a high-fat diet on telomere shortening and loss.