Network-Based Method for Inferring Cancer Progression at the Pathway Level from Cross-Sectional Mutation Data

IEEE/ACM Trans Comput Biol Bioinform. 2016 Nov-Dec;13(6):1036-1044. doi: 10.1109/TCBB.2016.2520934. Epub 2016 Feb 19.

Abstract

Large-scale cancer genomics projects are providing a wealth of somatic mutation data from a large number of cancer patients. However, it is difficult to obtain several samples with a temporal order from one patient in evaluating the cancer progression. Therefore, one of the most challenging problems arising from the data is to infer the temporal order of mutations across many patients. To solve the problem efficiently, we present a Network-based method (NetInf) to Infer cancer progression at the pathway level from cross-sectional data across many patients, leveraging on the exclusive property of driver mutations within a pathway and the property of linear progression between pathways. To assess the robustness of NetInf, we apply it on simulated data with the addition of different levels of noise. To verify the performance of NetInf, we apply it to analyze somatic mutation data from three real cancer studies with large number of samples. Experimental results reveal that the pathways detected by NetInf show significant enrichment. Our method reduces computational complexity by constructing gene networks without assigning the number of pathways, which also provides new insights on the temporal order of somatic mutations at the pathway level rather than at the gene level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • DNA Mutational Analysis / methods*
  • Disease Progression*
  • Gene Expression Regulation, Neoplastic / genetics
  • Genes, Neoplasm / genetics*
  • Genetic Markers / genetics
  • Humans
  • Neoplasm Proteins / genetics*
  • Neoplasms / genetics*
  • Signal Transduction / genetics*

Substances

  • Genetic Markers
  • Neoplasm Proteins