Understanding the complex structure of gene regulation, gene regulatory networks, and how those networks are altered in specific biological contexts, are all critical for developing effective, precision-medicine based therapeutic strategies. Integrating multi-omics data to model gene regulatory networks can provide unprecedented insights into the mechanisms underlying biological systems. Along these lines, our group has developed a suite of computational approaches that support: (1) effectively integrating multi-Omic data to model gene regulation; (2) performing network analysis to identify regulatory mechanisms mediating changes in biological state; and (3) linking regulatory alterations with patient phenotypes to support precision medicine. In this talk, I will review several specific applications in which we have used these methods to model complex regulatory processes and to gain specific insights into disease.