MOTIVATION: Biomarker discovery is an important topic in biomedical applications of computational biology, including applications such as gene and SNP selection from high-dimensional data. Surprisingly, the stability with respect to sampling variation or robustness of such selection processes has received attention only recently. However, robustness of biomarkers is an important issue, as it may greatly influence subsequent biological validations. In addition, a more robust set of markers may strengthen the confidence of an expert in the results of a selection method. RESULTS: Our first contribution is a general framework for the analysis of the robustness of a biomarker selection algorithm. Secondly, we conducted a large-scale analysis of the recently introduced concept of ensemble feature selection, where multiple feature selections are combined in order to increase the robustness of the final set of selected features. We focus on selection methods that are embedded in the estimation of support vector machines (SVMs). SVMs are powerful classification models that have shown state-of-the-art performance on several diagnosis and prognosis tasks on biological data. Their feature selection extensions also offered good results for gene selection tasks. We show that the robustness of SVMs for biomarker discovery can be substantially increased by using ensemble feature selection techniques, while at the same time improving upon classification performances. The proposed methodology is evaluated on four microarray datasets showing increases of up to almost 30% in robustness of the selected biomarkers, along with an improvement of approximately 15% in classification performance. The stability improvement with ensemble methods is particularly noticeable for small signature sizes (a few tens of genes), which is most relevant for the design of a diagnosis or prognosis model from a gene signature. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

This paper addresses feature selection techniques for classification of high dimensional data, such as those produced by microarray experiments. Some prior knowledge may be available in this context to bias the selection towards some dimensions (genes) a priori assumed to be more relevant. We propose a feature selection method making use of this partial supervision. It extends previous works on embedded feature selection with linear models including regularization to enforce sparsity. A practical approximation of this technique reduces to standard SVM learning with iterative rescaling of the inputs. The scaling factors depend here on the prior knowledge but the final selection may depart from it. Practical results on several microarray data sets show the benefits of the proposed approach in terms of the stability of the selected gene lists with improved classification performances.