Yang Li, Fan Wang, Rong Li, Yifan Sun 

【Publication Time】2020.04.13

【Lead Author】Yang Li

【Corresponding Author】Yifan Sun 

【Journal】 STATISTICAL METHODS IN MEDICAL RESEARCH

【Abstract】

In genomic analysis, it is significant though challenging to identify markers associated with cancer outcomes or phenotypes. Based on the biological mechanisms of cancers and the characteristics of datasets, we propose a novel integrative interaction approach under a semiparametric model, in which genetic and environmental factors are included as the parametric and nonparametric components, respectively. The goal of this approach is to identify the genetic factors and gene–gene interactions associated with cancer outcomes, while estimating the nonlinear effects of environmental factors. The proposed approach is based on the threshold gradient-directed regularisation technique. Simulation studies indicate that the proposed approach outperforms alternative methods at identifying the main effects and interactions, and has favourable estimation and prediction accuracy. We analysed non-small-cell lung carcinoma datasets from the Cancer Genome Atlas, and the results demonstrate that the proposed approach can identify markers with important implications and that it performs favourably in terms of prediction accuracy, identification stability, and computation cost.

【Keywords】

Heterogeneity, nonlinear model, strong hierarchy, the Cancer Genome Atlas, threshold gradient directed regularisation