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Åke Borg

Åke Borg

Principal investigator

Åke Borg

Reconstructing evolutionary trajectories of mutation signature activities in cancer using TrackSig

Author

  • Yulia Rubanova
  • Ruian Shi
  • Caitlin F Harrigan
  • Roujia Li
  • Jeff Wintersinger
  • Nil Sahin
  • Amit G Deshwar
  • Quaid D Morris

Other contributions

  • Åke Borg
  • Markus Ringnér
  • Johan Staaf

Summary, in English

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.

Department/s

  • LUCC: Lund University Cancer Centre
  • Familial Breast Cancer
  • Breastcancer-genetics
  • Molecular Cell Biology
  • Breast/lungcancer
  • Research Group Lung Cancer

Publishing year

2020-02-05

Language

English

Publication/Series

Nature Communications

Volume

11

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Medical Genetics

Keywords

  • Computational Biology/methods
  • Computer Simulation
  • Evolution, Molecular
  • Gene Frequency
  • Genome, Human
  • Humans
  • Mutation
  • Neoplasms/genetics
  • Polymorphism, Single Nucleotide
  • Whole Genome Sequencing

Status

Published

Research group

  • Familial Breast Cancer
  • Research Group Lung Cancer

ISBN/ISSN/Other

  • ISSN: 2041-1723