Incorporating biological networks into high-dimensional Bayesian survival analysis using an ICM/M algorithm

Abstract

The Cox proportional hazards model has been widely used in cancer genomic research that aims to identify genes from high-dimensional gene expression space associated with the survival time of patients. With the increase in expertly curated biological pathways, it is challenging to incorporate such complex networks in fitting a high-dimensional Cox model. This paper considers a Bayesian framework that employs the Ising prior to capturing relations among genes represented by graphs. A spike-and-slab prior is also assigned to each of the coefficients for the purpose of variable selection. The iterated conditional modes/medians (ICM/M) algorithm is proposed for the implementation for Cox models. The ICM/M estimates hyperparameters using conditional modes and obtains coefficients through conditional medians. This procedure produces some coefficients that are exactly zero, making the model more interpretable. Comparisons of the ICM/M and other regularized Cox models were carried out with both simulated and real data. Compared to lasso, adaptive lasso, elastic net, and DegreeCox, the ICM/M yielded more parsimonious models with consistent variable selection. The ICM/M model also provided a smaller number of false positives than the other methods and showed promising results in terms of predictive accuracy. In terms of computing times among the network-aware methods, the ICM/M algorithm is substantially faster than DegreeCox even when incorporating a large complex network. The implementation of the ICM/M algorithm for Cox regression model is provided in R package icmm, available on the Comprehensive R Archive Network (CRAN).