PCLasso: a protein complex-based, group lasso-Cox model for accurate prognosis and risk protein complex discovery

Abstract

For high-dimensional expression data, most prognostic models perform feature selection based on individual genes, which usually lead to unstable prognosis, and the identified risk genes are inherently insufficient in revealing complex molecular mechanisms. Since most genes carry out cellular functions by forming protein complexes-basic representatives of functional modules, identifying risk protein complexes may greatly improve our understanding of disease biology. Coupled with the fact that protein complexes have been shown to have innate resistance to batch effects and are effective predictors of disease phenotypes, constructing prognostic models and selecting features with protein complexes as the basic unit should improve the robustness and biological interpretability of the model. Here, we propose a protein complex-based, group lasso-Cox model (PCLasso) to predict patient prognosis and identify risk protein complexes. Experiments on three cancer types have proved that PCLasso has better prognostic performance than prognostic models based on individual genes. The resulting risk protein complexes not only contain individual risk genes but also incorporate close partners that synergize with them, which may promote the revealing of molecular mechanisms related to cancer progression from a comprehensive perspective. Furthermore, a pan-cancer prognostic analysis was performed to identify risk protein complexes of 19 cancer types, which may provide novel potential targets for cancer research.

Keywords: CoxPH model; group lasso; prognostic model; protein complex; random survival forest.