Affiliation:
1. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
2. Department of Mathematics and Statistics, Wright State University, Dayton, OH 45435, USA
Abstract
Abstract
Motivation
Cancer is a highly heterogeneous disease, and virtually all types of cancer have subtypes. Understanding the association between cancer subtypes and genetic variations is fundamental to the development of targeted therapies for patients. Somatic mutation plays important roles in tumor development and has emerged as a new type of genetic variations for studying the association with cancer subtypes. However, the low prevalence of individual mutations poses a tremendous challenge to the related statistical analysis.
Results
In this article, we propose an approach, subtype analysis with somatic mutations (SASOM), for the association analysis of cancer subtypes with somatic mutations. Our approach tests the association between a set of somatic mutations (from a genetic pathway) and subtypes, while incorporating functional information of the mutations into the analysis. We further propose a robust p-value combination procedure, DAPC, to synthesize statistical significance from different sources. Simulation studies show that the proposed approach has correct type I error and tends to be more powerful than possible alternative methods. In a real data application, we examine the somatic mutations from a cutaneous melanoma dataset, and identify a genetic pathway that is associated with immune-related subtypes.
Availability and implementation
The SASOM R package is available at https://github.com/rksyouyou/SASOM-pkg. R scripts and data are available at https://github.com/rksyouyou/SASOM-analysis.
Supplementary information
Supplementary data are available at Bioinformatics online.
Funder
U.S. National Institutes of Health
Fred Hutch
ORIP
Publisher
Oxford University Press (OUP)
Subject
Computational Mathematics,Computational Theory and Mathematics,Computer Science Applications,Molecular Biology,Biochemistry,Statistics and Probability
Cited by
6 articles.
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