Transition dependency: a gene-gene interaction measure for times series microarray data.

Gene-Gene dependency plays a very important role in system biology as it pertains to the crucial understanding of different biological mechanisms. Time-course microarray data provides a new platform useful to reveal the dynamic mechanism of gene-gene dependencies. Existing interaction measures are mostly based on association measures, such as Pearson or Spearman correlations. However, it is well known that such interaction measures can only capture linear or monotonic dependency relationships but not for nonlinear combinatorial dependency relationships. With the invocation of hidden Markov models, we propose a new measure of pairwise dependency based on transition probabilities. The new dynamic interaction measure checks whether or not the joint transition kernel of the bivariate state variables is the product of two marginal transition kernels. This new measure enables us not only to evaluate the strength, but also to infer the details of gene dependencies. It reveals nonlinear combinatorial dependency structure in two aspects: between two genes and across adjacent time points. We conduct a bootstrap-based chi(2) test for presence/absence of the dependency between every pair of genes. Simulation studies and real biological data analysis demonstrate the application of the proposed method. The software package is available under request.