eprintid: 26510 rev_number: 10 eprint_status: archive userid: 1589 dir: disk0/00/02/65/10 datestamp: 2019-08-06 12:10:28 lastmod: 2019-08-22 08:36:51 status_changed: 2019-08-06 12:10:28 type: article metadata_visibility: show creators_name: Feuerbach, Lars creators_name: Sieverling, Lina creators_name: Deeg, Katharina I. creators_name: Ginsbach, Philip creators_name: Hutter, Barbara creators_name: Buchhalter, Ivo creators_name: Northcott, Paul A. creators_name: Mughal, Sadaf S. creators_name: Chudasama, Priya creators_name: Glimm, Hanno creators_name: Scholl, Claudia creators_name: Lichter, Peter creators_name: Fröhling, Stefan creators_name: Pfister, Stefan M. creators_name: Jones, David T. W. creators_name: Rippe, Karsten creators_name: Brors, Benedikt title: TelomereHunter – in silico estimation of telomere content and composition from cancer genomes subjects: 610 divisions: 850300 abstract: 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. date: 2019 publisher: BioMed Central ; Springer ppn_swb: 1671840720 own_urn: urn:nbn:de:bsz:16-heidok-265107 language: eng bibsort: FEUERBACHLTELOMEREHU2019 full_text_status: public publication: BMC Bioinformatics volume: 20 number: 272 place_of_pub: London ; Berlin, Heidelberg pagerange: 1-11 issn: 1471-2105 citation: Feuerbach, Lars ; Sieverling, Lina ; Deeg, Katharina I. ; Ginsbach, Philip ; Hutter, Barbara ; Buchhalter, Ivo ; Northcott, Paul A. ; Mughal, Sadaf S. ; Chudasama, Priya ; Glimm, Hanno ; Scholl, Claudia ; Lichter, Peter ; Fröhling, Stefan ; Pfister, Stefan M. ; Jones, David T. W. ; Rippe, Karsten ; Brors, Benedikt (2019) TelomereHunter – in silico estimation of telomere content and composition from cancer genomes. BMC Bioinformatics, 20 (272). pp. 1-11. ISSN 1471-2105 document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/26510/1/12859_2019_Article_2851.pdf