Automated Formal Reasoning to Uncover Molecular Programs of Self-Renewal

The Reasoning Engine for Interaction Networks (RE:IN) is a tool that was developed initially for the study of pluripotency in mouse embryonic stem cells. A set of critical factors that regulate the pluripotent state had been identified experimentally, but it was not known how these genes interacted to stabilize self-renewal or commit the cell to differentiation. The methodology encapsulated in RE:IN enabled the exploration of a space of possible network interaction models, allowing for uncertainty in whether individual interactions exist between the pluripotency factors. This concept of an "abstract" network was combined with automated reasoning that allows the user to eliminate models that are inconsistent with experimental observations. The tool generalizes beyond the study of stem cell decision-making, allowing for the study of interaction networks more broadly across biology.