Discovering Pair-wise Synergies in Microarray Data

Informative gene selection can have important implications for the improvement of cancer diagnosis and the identification of new drug targets. Individual-gene-ranking methods ignore interactions between genes. Furthermore, popular pair-wise gene evaluation methods, e.g. TSP and TSG, are helpless for discovering pair-wise interactions. Several efforts to discover pair-wise synergy have been made based on the information approach, such as EMBP and FeatKNN. However, the methods which are employed to estimate mutual information, e.g. binarization, histogram-based and KNN estimators, depend on known data or domain characteristics. Recently, Reshef et al. proposed a novel maximal information coefficient (MIC) measure to capture a wide range of associations between two variables that has the property of generality. An extension from MIC(X; Y) to MIC(X(1); X(2); Y) is therefore desired. We developed an approximation algorithm for estimating MIC(X(1); X(2); Y) where Y is a discrete variable. MIC(X(1); X(2); Y) is employed to detect pair-wise synergy in simulation and cancer microarray data. The results indicate that MIC(X(1); X(2); Y) also has the property of generality. It can discover synergic genes that are undetectable by reference feature selection methods such as MIC(X; Y) and TSG. Synergic genes can distinguish different phenotypes. Finally, the biological relevance of these synergic genes is validated with GO annotation and OUgene database.