title: Comparative analysis of whole genome sequencing-based telomere length measurement techniques.
abstract: Telomeres are regions of repetitive DNA at the ends of human chromosomes that function to maintain the integrity of the genome. Telomere attrition is associated with cellular ageing, whilst telomere maintenance is a prerequisite for malignant transformation. Whole genome sequencing (WGS) captures sequence information from the entire genome, including the telomeres, and is increasingly being applied in research and in the clinic. Several bioinformatics tools have been designed to determine telomere content and length from WGS data, and include Motif_counter, TelSeq, Computel, qMotif, and Telomerecat. These tools utilise different approaches to identify, quantify and normalise telomeric reads; however, it is not known how they compare to one another. Here we describe the details and utility of each tool, and directly compare WGS telomere length output with laboratory-based telomere length measurements. In addition, we evaluate the accessibility, practicality, speed, and additional features of each tool. Each tool was tested using a range of telomere read extraction criteria, to determine the optimal parameters for the specific WGS read length. The aim of this article is to improve the accessibility of WGS telomere length measurement tools, which have the potential to be applied to WGS cohorts for clinical as well as research benefit.
authors: Telomere Length Regulation Group, Children's Medical Research Institute, The University of Sydney, Westmead, NSW, Australia.
authors: Michael
authors: M
authors: Lee
authors: Cancer Research Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW, Australia.
authors: Christine E
authors: CE
authors: Napier
authors: Telomere Length Regulation Group, Children's Medical Research Institute, The University of Sydney, Westmead, NSW, Australia.
authors: Sile F
authors: SF
authors: Yang
authors: Bioinformatics Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW, Australia.
authors: Jonathan W
authors: JW
authors: Arthur
authors: Cancer Research Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW, Australia.
authors: Roger R
authors: RR
authors: Reddel
authors: Telomere Length Regulation Group, Children's Medical Research Institute, The University of Sydney, Westmead, NSW, Australia. Electronic address: hpickett@cmri.org.au.
authors: Hilda A
authors: HA
authors: Pickett
mesh_terms: D016922:Cellular Senescence; D019295:Computational Biology / Q000379:methods; D015894:Genome, Human; D006801:Humans; D012984:Software; D059505:Telomere Homeostasis; D000073336:Whole Genome Sequencing / Q000379:methods*
keywords: Computel; Motif_counter; TelSeq; Telomere length; WGS; qMotif