TY  - JOUR
JF  - BMC Bioinformatics
SP  - 1
Y1  - 2019///
TI  - TelomereHunter ? in silico estimation of telomere content and composition from cancer genomes
EP  - 11
IS  - 272
PB  - BioMed Central ; Springer
AV  - public
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/26510/
SN  - 1471-2105
A1  - Feuerbach, Lars
A1  - Sieverling, Lina
A1  - Deeg, Katharina I.
A1  - Ginsbach, Philip
A1  - Hutter, Barbara
A1  - Buchhalter, Ivo
A1  - Northcott, Paul A.
A1  - Mughal, Sadaf S.
A1  - Chudasama, Priya
A1  - Glimm, Hanno
A1  - Scholl, Claudia
A1  - Lichter, Peter
A1  - Fröhling, Stefan
A1  - Pfister, Stefan M.
A1  - Jones, David T. W.
A1  - Rippe, Karsten
A1  - Brors, Benedikt
CY  - London ; Berlin, Heidelberg
VL  - 20
ID  - heidok26510
N2  - Background: Establishment of telomere maintenance mechanisms is a universal step in tumor development to achieve replicative immortality. These processes leave molecular footprints in cancer genomes in the form of altered telomere content and aberrations in telomere composition. To retrieve these telomere characteristics from high-throughput sequencing data the available computational approaches need to be extended and optimized to fully exploit the information provided by large scale cancer genome data sets.

Results: We here present TelomereHunter, a software for the detailed characterization of telomere maintenance mechanism footprints in the genome. The tool is implemented for the analysis of large cancer genome cohorts and provides a variety of diagnostic diagrams as well as machine-readable output for subsequent analysis. A novel key feature is the extraction of singleton telomere variant repeats, which improves the identification and subclassification of the alternative lengthening of telomeres phenotype. We find that whole genome sequencing-derived telomere content estimates strongly correlate with telomere qPCR measurements (r?=?0.94). For the first time, we determine the correlation of in silico telomere content quantification from whole genome sequencing and whole genome bisulfite sequencing data derived from the same tumor sample (r?=?0.78). An analogous comparison of whole exome sequencing data and whole genome sequencing data measured slightly lower correlation (r?=?0.79). However, this is considerably improved by normalization with matched controls (r?=?0.91).

Conclusions: TelomereHunter provides new functionality for the analysis of the footprints of telomere maintenance mechanisms in cancer genomes. Besides whole genome sequencing, whole exome sequencing and whole genome bisulfite sequencing are suited for in silico telomere content quantification, especially if matched control samples are available. The software runs under a GPL license and is available at https://www.dkfz.de/en/applied-bioinformatics/telomerehunter/telomerehunter.html.
ER  -