Reconstructing evolutionary trajectories of mutation signature activities in cancer using TrackSig.
Authors
Rubanova, Yulia
Shi, Ruian
Li, Roujia
Wintersinger, Jeff
Sahin, Nil
Deshwar, Amit
PCAWG Evolution and Heterogeneity Working Group
PCAWG Consortium
Publication Date
2020-02-05Journal Title
Nat Commun
ISSN
2041-1723
Publisher
Springer Science and Business Media LLC
Volume
11
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Rubanova, Y., Shi, R., Harrigan, C. F., Li, R., Wintersinger, J., Sahin, N., Deshwar, A., et al. (2020). Reconstructing evolutionary trajectories of mutation signature activities in cancer using TrackSig.. Nat Commun, 11 (1) https://doi.org/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.
Keywords
Article, /631/67/68, /631/114/2397, article
Identifiers
s41467-020-14352-7, 14352
External DOI: https://doi.org/10.1038/s41467-020-14352-7
This record's URL: https://www.repository.cam.ac.uk/handle/1810/317152
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
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