Practical Guidelines for Incorporating Knowledge-Based and Data-Driven Strategies into the Inference of Gene Regulatory Networks.

Modeling gene regulatory networks (GRNs) is essential for conceptualizing how genes are expressed and how they influence each other. Typically, a reverse engineering approach is employed; this strategy is effective in reproducing possible fitting models of GRNs. To use this strategy, however, two daunting tasks must be undertaken: one task is to optimize the accuracy of inferred network behaviors; and the other task is to designate valid biological topologies for target networks. Although existing studies have addressed these two tasks for years, few of the studies can satisfy both of the requirements simultaneously. To address these difficulties, we propose an integrative modeling framework that combines knowledge-based and data-driven input sources to construct biological topologies with their corresponding network behaviors. To validate the proposed approach, a real dataset collected from the cell cycle of the yeast S. cerevisiae is used. The results show that the proposed framework can successfully infer solutions that meet the requirements of both the network behaviors and biological structures. Therefore, the outcomes are exploitable for future in vivo experimental design.