Utilizing patient information to identify subtype heterogeneity of cancer driver genes

Ho Hsiang Wu, Xing Hua, Jianxin Shi, Nilanjan Chatterjee, Bin Zhu

Research output: Contribution to journalArticlepeer-review

Abstract

Identifying cancer driver genes is essential for understanding the mechanisms of carcinogenesis and designing therapeutic strategies. Although driver genes have been identified for many cancer types, it is still not clear whether the selection pressure of driver genes is homogeneous across cancer subtypes. We propose a statistical framework MutScot to improve the identification of driver genes and to investigate the heterogeneity of driver genes across cancer subtypes. Through simulation studies, we show that MutScot properly controls the type I error in detecting driver genes. In addition, we demonstrate that MutScot can identify subtype heterogeneity of driver genes. Applications to three studies in The Cancer Genome Atlas (TCGA) project showcase that MutScot has a desirable sensitivity for detecting driver genes and that MutScot identifies subtype heterogeneity of driver genes in breast cancer and lung cancer with regards to the status of hormone receptor and to the smoking status, respectively.

Original languageEnglish (US)
Pages (from-to)510-519
Number of pages10
JournalStatistical Methods in Medical Research
Volume31
Issue number3
DOIs
StatePublished - Mar 2022

Keywords

  • Somatic mutations
  • cancer subtype
  • driver genes
  • patient heterogeneity

ASJC Scopus subject areas

  • Health Information Management
  • Epidemiology
  • Statistics and Probability

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