Comprehensive Evaluation of Composite Gene Features in Cancer Outcome Prediction

Owing to the heterogeneous and continuously evolving nature of cancers, classifiers based on the expression of individual genes usually do not result in robust prediction of cancer outcome. As an alternative, composite gene features that combine functionally related genes have been proposed. It is expected that such features can be more robust and reproducible since they can capture the alterations in relevant biological processes as a whole and may be less sensitive to fluctuations in the expression of individual genes. Various algorithms have been developed for the identification of composite features and inference of composite gene feature activity, which all claim to improve the prediction accuracy. However, because of the limitations of test datasets incorporated by each individual study and inconsistent test procedures, the results of these studies are sometimes conflicting and unproducible. For this reason, it is difficult to have a comprehensive understanding of the prediction performance of composite gene features, particularly across different cancers, cancer subtypes, and cohorts. In this study, we implement various algorithms for the identification of composite gene features and their utilization in cancer outcome prediction, and perform extensive comparison and evaluation using seven microarray datasets covering two cancer types and three different phenotypes. Our results show that, while some algorithms outperform others for certain classification tasks, no single algorithm consistently outperforms other algorithms and individual gene features.