SURVIV for survival analysis of mRNA isoform variation.
The rapid accumulation of clinical RNA-seq data sets has provided the opportunity to associate mRNA isoform variations to clinical outcomes. Here we report a statistical method SURVIV (Survival analysis of mRNA Isoform Variation), designed for identifying mRNA isoform variation associated with patient survival time. A unique feature and major strength of SURVIV is that it models the measurement uncertainty of mRNA isoform ratio in RNA-seq data. Simulation studies suggest that SURVIV outperforms the conventional Cox regression survival analysis, especially for data sets with modest sequencing depth. We applied SURVIV to TCGA RNA-seq data of invasive ductal carcinoma as well as five additional cancer types. Alternative splicing-based survival predictors consistently outperform gene expression-based survival predictors, and the integration of clinical, gene expression and alternative splicing profiles leads to the best survival prediction. We anticipate that SURVIV will have broad utilities for analysing diverse types of mRNA isoform variation in large-scale clinical RNA-seq projects.
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California 90095, USA.
Shihao
S
Shen
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California 90095, USA.
Yuanyuan
Y
Wang
Bioinformatics Interdepartmental Graduate Program, University of California, Los Angeles, Los Angeles, California 90095, USA.
Chengyang
C
Wang
Department of Statistics, University of California, Los Angeles, Los Angeles, California 90095, USA.
Ying Nian
YN
Wu
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California 90095, USA.
Yi
Y
Xing
D017398:Alternative Splicing; D001943:Breast Neoplasms / Q000209:etiology* / Q000401:mortality; D018270:Carcinoma, Ductal, Breast / Q000209:etiology* / Q000401:mortality; D006801:Humans; D015233:Models, Statistical; D059368:RNA Isoforms; D016019:Survival Analysis
D059368:RNA Isoforms