Counterfactual Resimulation for Causal Analysis of Rule-Based Models

Models based on rules that express local and heterogeneous mechanisms of stochastic interactions between structured agents are an important tool for investigating the dynamical behavior of complex systems, especially in molecular biology. Given a simulated trace of events, the challenge is to construct a causal diagram that explains how a phenomenon of interest occurred. Counterfactual analysis can provide distinctive insights, but its standard definition is not applicable in rule-based models because they are not readily expressible in terms of structural equations. We provide a semantics of counterfactual statements that addresses this challenge by sampling counterfactual trajectories that are probabilistically as close to the factual trace as a given intervention permits them to be. We then show how counterfactual dependencies give rise to explanations in terms of relations of enablement and prevention between events.