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BMC Bioinformatics. 2019 May 28;20(1):272. doi: 10.1186/s12859-019-2851-0.

TelomereHunter - in silico estimation of telomere content and composition from cancer genomes.

Author information

1
Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. l.feuerbach@dkfz-heidelberg.de.
2
Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
3
Faculty of Biosciences, Heidelberg University, 69120, Heidelberg, Germany.
4
Research Group Genome Organization & Function/Division of Chromatin Networks, German Cancer Research Center (DKFZ) and BioQuant Center, 69120, Heidelberg, Germany.
5
Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
6
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
7
Division of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
8
Translational Functional Cancer Genomics, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
9
Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden, University Hospital Carl Gustav Carus, Dresden and DKFZ, Heidelberg, Germany.
10
German Cancer Consortium (DKTK), 69120, Heidelberg, Germany.
11
Division of Applied Functional Genomics, DKFZ, 69120, Heidelberg, Germany.
12
Division of Molecular Genetics, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
13
Hopp Children's Cancer Center at the NCT Heidelberg (KiTZ), 69120, Heidelberg, Germany.
14
Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, 69120, Heidelberg, Germany.
15
Pediatric Glioma Research Group, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.

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 .

PMID:
31138115
PMCID:
PMC6540518
DOI:
10.1186/s12859-019-2851-0
[Indexed for MEDLINE]
Free PMC Article

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