TASeR: A bioinformatic pipeline for Telomere Analysis from Sequence Reads

Telomeres are the repetitive sequence at the ends of chromosomes.  This sequence associates with six proteins to form the shelterin complex, which protects the ends of chromosomes from being recognized as double strand breaks.   Average telomere length is a highly variable, inherited trait as well as a biomarker for biological aging.  Accelerated somatic telomere reduction, loss, and dysfunction are characteristic of a wide range of human diseases, including cancer. These DNA regions are highly variable, and contain sequence elements believed to be essential for TERRA transcription, regulation of telomere length, and epigenetic regulation of telomeric chromatin function.  Telomeric and subtelomeric sequences contain both characteristic simple repeats and a set of well-characterized low-copy sequence elements; however, because they are both multicopy and variable between genomes they are typically not included in analyses of Next-generation datasets because these reads do not map uniquely to the assembled genome.  We have created TASeR to selectively capture and analyze in detail the telomeric fraction of genome-wide next-generation sequence data, using our current understanding of telomeric sequence organization. These novel approaches analyze telomeric and subtelomeric read data to assess telomere length, and mutation.  This analysis has replicated results demonstrating telomere changes in cancer, a shorter telomere tract in cancer samples, and provided finer detail, increased mutation and interspersion of mutations in the telomere tract.  This pipeline will be expanded to analyze sequence features of the subtelomere and specific chromosome ends.