Integrative analysis of somatic mutations and transcriptomic data to functionally stratify breast cancer patients

BMC Genomics

Research

Jie Zhang¹  Kun Huang¹  Jeffrey D. Parvin¹  Zachary Abrams¹ 

[1] Department of Biomedical Informatics, The Ohio State University, 43210, Columbus, OH, USA;

关键词: Distance correlation;    Breast cancer patient stratification;    Functional analysis of somatic mutation;    Integrative analysis;   

DOI  :  10.1186/s12864-016-2902-0

来源: Springer

【 摘 要 】

BackgroundSomatic mutations can be used as potential biomarkers for subtyping and predicting outcomes for cancer patients. However, cancer patients often carry many somatic mutations, which do not always concentrate on specific genomic loci, suggesting that the mutations may affect common pathways or gene interaction networks instead of common genes. The challenge is thus to identify the functional relationships among the mutations using multi-modal data. We developed a novel approach for integrating patient somatic mutation, transcriptome and clinical data to mine underlying functional gene groups that can be used to stratify cancer patients into groups with different clinical outcomes. Specifically, we use distance correlation metric to mine the correlations between expression profiles of mutated genes from different patients.ResultsWith this approach, we were able to cluster patients based on the functional relationships between the affected genes using their expression profiles, and to visualize the results using multi-dimensional scaling. Interestingly, we identified a stable subgroup of breast cancer patients that are highly enriched with ER-negative and triple-negative subtypes, and the somatic mutation genes they harbor were capable of acting as potential biomarkers to predict patient survival in several different breast cancer datasets, especially in ER-negative cohorts which has lacked reliable biomarkers.ConclusionsOur method provides a novel and promising approach for integrating genotyping and gene expression data in patient stratification in complex diseases.

【 授权许可】

CC BY   
© The Author(s). 2016

【 图 表 】

12864_2015_2296_Article_IEq87.gif

12864_2017_3742_Article_IEq1.gif

12864_2016_3440_Article_IEq18.gif

12864_2017_4269_Article_IEq9.gif

12864_2016_3440_Article_IEq16.gif