Semiparametric integrative interaction analysis for non-small-cell lung cancer

TL;DR

This paper introduces a semiparametric integrative interaction method for identifying genetic and environmental factors associated with non-small-cell lung cancer, improving detection accuracy and interpretability.

Contribution

It proposes a novel semiparametric model with TGDR for better detection of gene interactions and environmental effects in cancer genomics.

Findings

Outperforms existing methods in simulation studies

Accurately identifies cancer-related genetic markers

Shows stable and cost-effective analysis on TCGA NSCLC data

Abstract

In the genomic analysis, it is significant while challenging to identify markers associated with cancer outcomes or phenotypes. Based on the biological mechanisms of cancers and the characteristics of datasets as well, this paper proposes a novel integrative interaction approach under the semiparametric model, in which the genetic factors 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, and meanwhile, estimate the nonlinear effects of environmental factors. The proposed approach is based on the threshold gradient directed regularization (TGDR) technique. Simulation studies indicate that the proposed approach outperforms in the identification of main effects and interactions, and has favorable estimation and prediction accuracy compared with the alternative methods. The analysis of non-small-cell lung carcinomas (NSCLC) datasets from The Cancer Genome Atlas (TCGA) are conducted, showing that the proposed approach can identify markers with important implications and have favorable performance in prediction accuracy, identification stability, and computation cost.