Feature construction from synergic pairs to improve microarray-based classification

MOTIVATION Microarray experiments that allow simultaneous expression profiling of thousands of genes in various conditions (tissues, cells or time) generate data whose analysis raises difficult problems. In particular, there is a vast disproportion between the number of attributes (tens of thousands) and the number of examples (several tens). Dimension reduction is therefore a key step before applying classification approaches. Many methods have been proposed to this purpose, but only a few of them considered a direct quantification of transcriptional interactions. We describe and experimentally validate a new dimension reduction and feature construction method, which assesses interactions between expression profiles to improve microarray-based classification accuracy. RESULTS Our approach relies on a mutual information measure that exposes some elementary constituents of the information contained in a pair of gene expression profiles. We show that their analysis implies a term that represents the information of the interaction between the two genes. The principle of our method, called FeatKNN, is to exploit the information provided by highly synergic gene pairs to improve classification accuracy. First, a heuristic search selects the most informative gene pairs. Then, for each selected pair, a new feature, representing the classification margin of a KNN classifier in the gene pairs space, is constructed. We show experimentally that the interactional information has a degree of significance comparable to that of the gene expression profiles considered separately. Our method has been tested with different classifiers and yielded significant improvements in accuracy on several public microarray databases. Moreover, a synthetic assessment of the biological significance of the concept of synergic gene pairs suggested its ability to uncover relevant mechanisms underlying interactions among various cellular processes.