C-mix: A high-dimensional mixture model for censored durations, with applications to genetic data

Abstract

We introduce a supervised learning mixture model for censored durations (C-mix) to simultaneously detect subgroups of patients with different prognosis and order them based on their risk. Our method is applicable in a high-dimensional setting, i.e. with a large number of biomedical covariates. Indeed, we penalize the negative log-likelihood by the Elastic-Net, which leads to a sparse parameterization of the model and automatically pinpoints the relevant covariates for the survival prediction. Inference is achieved using an efficient Quasi-Newton Expectation Maximization algorithm, for which we provide convergence properties. The statistical performance of the method is examined on an extensive Monte Carlo simulation study and finally illustrated on three publicly available genetic cancer datasets with high-dimensional covariates. We show that our approach outperforms the state-of-the-art survival models in this context, namely both the CURE and Cox proportional hazards models penalized by the Elastic-Net, in terms of C-index, AUC( t) and survival prediction. Thus, we propose a powerful tool for personalized medicine in cancerology.