Journal Article

DKFZ-2021-02570

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Reconstructing evolutionary trajectories of mutation signature activities in cancer using TrackSig.

Rubanova, Y. ; Shi, R. ; Harrigan, C. F. ; Li, R. ; Wintersinger, J. ; Sahin, N. ; Deshwar, A. ; PCAWGEvolution ; Group, H. W. ; Morris, Q. ; PCAWGConsortium

2020
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-020-14352-7

Abstract: The type and genomic context of cancer mutations depend on their causes. These causes have been characterized using signatures that represent mutation types that co-occur in the same tumours. However, it remains unclear how mutation processes change during cancer evolution due to the lack of reliable methods to reconstruct evolutionary trajectories of mutational signature activity. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data from 2658 cancers across 38 tumour types, we present TrackSig, a new method that reconstructs these trajectories using optimal, joint segmentation and deconvolution of mutation type and allele frequencies from a single tumour sample. In simulations, we find TrackSig has a 3-5% activity reconstruction error, and 12% false detection rate. It outperforms an aggressive baseline in situations with branching evolution, CNA gain, and neutral mutations. Applied to data from 2658 tumours and 38 cancer types, TrackSig permits pan-cancer insight into evolutionary changes in mutational processes.

Keyword(s): Computational Biology: methods (MeSH) ; Computer Simulation (MeSH) ; Evolution, Molecular (MeSH) ; Gene Frequency (MeSH) ; Genome, Human (MeSH) ; Humans (MeSH) ; Mutation (MeSH) ; Neoplasms: genetics (MeSH) ; Neoplasms: pathology (MeSH) ; Polymorphism, Single Nucleotide (MeSH) ; Whole Genome Sequencing (MeSH)

Note: siehe Correction: DKFZ Autoren affiliiert im PCAWG Consortium: https://inrepo02.dkfz.de/record/212434 / https://doi.org/10.1038/s41467-022-32336-7

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Contributing Institute(s):

1. Epigenomik (B370)
2. Angewandte Bioinformatik (B330)
3. Bioinformatik und Omics Data Analytics (B240)
4. DKTK HD zentral (HD01)
5. Theoretische Bioinformatik (B080)
6. B060 Molekulare Genetik (B060)
7. B062 Pädiatrische Neuroonkologie (B062)
8. Pädiatrische Gliomforschung (B360)
9. B260 Bioinformatik der Genomik und Systemgenetik (B260)
10. DKTK Koordinierungsstelle Berlin (BE01)
11. B063 Krebsgenomforschung (B063)
12. B087 Neuroblastom Genomik (B087)
13. Core Facility Omics IT (W610)
14. Hochdurchsatz-Sequenzierung (W190)
15. B066 Chromatin-Netzwerke (B066)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2020

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