phyC: Clustering cancer evolutionary trees

PLoS Comput Biol. 2017 May 1;13(5):e1005509. doi: 10.1371/journal.pcbi.1005509. eCollection 2017 May.

Abstract

Multi-regional sequencing provides new opportunities to investigate genetic heterogeneity within or between common tumors from an evolutionary perspective. Several state-of-the-art methods have been proposed for reconstructing cancer evolutionary trees based on multi-regional sequencing data to develop models of cancer evolution. However, there have been few studies on comparisons of a set of cancer evolutionary trees. We propose a clustering method (phyC) for cancer evolutionary trees, in which sub-groups of the trees are identified based on topology and edge length attributes. For interpretation, we also propose a method for evaluating the sub-clonal diversity of trees in the clusters, which provides insight into the acceleration of sub-clonal expansion. Simulation showed that the proposed method can detect true clusters with sufficient accuracy. Application of the method to actual multi-regional sequencing data of clear cell renal carcinoma and non-small cell lung cancer allowed for the detection of clusters related to cancer type or phenotype. phyC is implemented with R(≥3.2.2) and is available from https://github.com/ymatts/phyC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma, Renal Cell
  • Cluster Analysis*
  • Computational Biology
  • Evolution, Molecular*
  • Humans
  • Lung Neoplasms
  • Neoplasms / classification*
  • Neoplasms / genetics*
  • Software*

Grants and funding

This work was supported by 16K16146, 16H01572, 15H05707 from The Japan Society for the Promotion of Science (http://www.jsps.go.jp/english/e-grants/grants01.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.