Detecting Pathway Cross-Talks by Analyzing Conserved Functional Modules across Multiple Phenotype-Expressing Organisms

Biological systems are organized hierarchically, starting from the protein level and expanding to pathway or even higher levels. Understanding interactions at lower levels (proteins interactions) in the hierarchy will help us understand interactions at higher levels (pathway cross-talks). Identifying cross-talks that are related to the expression of a particular phenotype will be of interest to genetic engineers, because it will provide information on how different cellular subsystems could work together to express a phenotype. Current research has typically focused on identifying genotype-phenotype associations or pathway-phenotype associations. In contrast, we developed a method to identify phenotype-related pathway cross talks by obtaining conserved groups of interacting proteins (functional modules). By applying our method to two groups of hydrogen producing organisms (light fermentation and dark fermentation), we have shown that our method effectively unearths known pathway cross-talks that are important to hydrogen production.