Assieh Saadatpour

Mathematical modeling of biological processes provides deep insights into complex cellular systems. While quantitative and continuous models such as differential equations have been widely used, their use is obstructed in systems wherein the knowledge of mechanistic details and kinetic parameters is scarce. On the other hand, a wealth of molecular level qualitative data on individual components and interactions can be obtained from the experimental literature and high-throughput technologies, making qualitative approaches such as Boolean network modeling extremely useful. In this paper, we build on our research to provide a methodology overview of Boolean modeling in systems biology, including Boolean dynamic modeling of cellular networks, attractor analysis of Boolean dynamic models, as well as inferring biological regulatory mechanisms from high-throughput data using Boolean models. We finally demonstrate how Boolean models can be applied to perform the structural analysis of cellular networks. This overview aims to acquaint life science researchers with the basic steps of Boolean modeling and its applications in several areas of systems biology.

Recent progress in single-cell technologies has enabled the identification of all major cell types in mouse. However, for most cell types, the regulatory mechanism underlying their identity remains poorly understood. By computational analysis of the recently published mouse cell atlas data, we have identified 202 regulons whose activities are highly variable across different cell types, and more importantly, predicted a small set of essential regulators for each major cell type in mouse. Systematic validation by automated literature and data mining provides strong additional support for our predictions. Thus, these predictions serve as a valuable resource that would be useful for the broad biological community. Finally, we have built a user-friendly, interactive web portal to enable users to navigate this mouse cell network atlas.