Elucidation of Genetic Interactions in the Yeast GATA-Factor Network Using Bayesian Model Selection

Gene regulatory networks underlie all key processes that enable a cell to maintain long-term homeostasis in a changing environment. Understanding the structure and function of complex gene networks is an experimentally difficult and error-prone procedure. Mechanistic mathematical modeling promises to alleviate these problems, as we demonstrate here for the yeast GATA-factor network, the central controller of the cellular response to nitrogen source quality. Despite years of targeted studies, the interaction pattern of this network is still not known precisely. To resolve several still-remaining ambiguities, we generated a set of alternative mathematical models, and compared them against each other using Bayesian model selection based on dynamic gene expression data. The top-ranking model was then validated on a separate, newly generated dataset. Our work thus provides new insights to the mechanism of nitrogen regulation in yeast, while at the same time overcoming some key computational inference problems for large models in systems biology.