Improved microarray-based decision support with graph encoded interactome data.

Abstract

In the past, microarray studies have been criticized due to noise and the limited overlap between gene signatures. Prior biological knowledge should therefore be incorporated as side information in models based on gene expression data to improve the accuracy of diagnosis and prognosis in cancer. As prior knowledge, we investigated interaction and pathway information from the human interactome on different aspects of biological systems. By exploiting the properties of kernel methods, relations between genes with similar functions but active in alternative pathways could be incorporated in a support vector machine classifier based on spectral graph theory. Using 10 microarray data sets, we first reduced the number of data sources relevant for multiple cancer types and outcomes. Three sources on metabolic pathway information (KEGG), protein-protein interactions (OPHID) and miRNA-gene targeting (microRNA.org) outperformed the other sources with regard to the considered class of models. Both fixed and adaptive approaches were subsequently considered to combine the three corresponding classifiers. Averaging the predictions of these classifiers performed best and was significantly better than the model based on microarray data only. These results were confirmed on 6 validation microarray sets, with a significantly improved performance in 4 of them. Integrating interactome data thus improves classification of cancer outcome for the investigated microarray technologies and cancer types. Moreover, this strategy can be incorporated in any kernel method or non-linear version of a non-kernel method.