Large-scale analysis of expression signatures reveals hidden links among diverse cellular processes

We identified 7,419 statistically significant overlaps between various published gene lists. Most (80%) of the overlaps can be represented by a highly connected network, a "molecular signature map," that highlights the correlation of various expression signatures. By dissecting this network, we identified sub-networks that define clusters of gene sets related to common biological processes (cell cycle, immune response, etc). Examination of these sub-networks has confirmed relationships among various pathways and also generated new hypotheses. For example, our result suggests that glutamine deficiency might suppress cellular growth by inhibiting the MYC pathway. Interestingly, we also observed 1,369 significant overlaps between a set of genes upregulated by factor X and a set of genes downregulated by factor Y, suggesting a repressive interaction between X and Y factors.Our results suggest that molecular-level responses to diverse chemical and genetic perturbations are heavily interconnected in a modular fashion. Also, shared molecular pathways can be identified by comparing newly defined gene expression signatures with databases of previously published gene expression signatures.With a limited number of genes, cells have to effectively coordinate their responses to diverse perturbations. Different stimuli could activate the same molecular pathways and thus induce overlapping sets of genes. A classic example is response to cold, drought and salt stress in plants [1]. Evoking an opposite response might be beneficial in other circumstances. The MYC pathway, for example, induces proliferative growth under favourable conditions, but is suppressed by many stresses such as inflammation [2]. Studying correlations between these diverse responses compliments in-depth investigations focused on cellular responses to individual stimuli and will enhance understanding of complex regulatory mechanisms.There are many examples of the co-regulation of the same set of genes in differen