This manuscript contributes a general and practical framework for casting a Markov process model of a system at equilibrium as a structural causal model, and carrying out counterfactual inference. Markov processes mathematically describe the mechanisms in the system, and predict the system's equilibrium behavior upon intervention, but do not support counterfactual inference. In contrast, structural causal models support counterfactual inference, but do not identify the mechanisms.

An important aspect of studying these systems is predicting the equilibrium behavior of the system upon an intervention, and selecting high-value interventions.

An important aspect of studying these systems is predicting the equilibrium behavior of the system upon an intervention, and selecting high-value interventions.

We thank the reviewers for the constructive feedback and are happy to provide clarifications. We would like to stress the benefit of this work. The counterfactual policy evaluation is useful in two ways. Due to the space constraint of this letter, we answer three of Reviewer 3's broader questions. Reviewer 3 asks about extensions to cyclic graphs.

This manuscript contributes a general and practical framework for casting a Markov process model of a system at equilibrium as a structural causal model, and carrying out counterfactual inference. Markov processes mathematically describe the mechanisms in the system, and predict the system's equilibrium behavior upon intervention, but do not support counterfactual inference. In contrast, structural causal models support counterfactual inference, but do not identify the mechanisms. We define the structural causal models in terms of the parameters and the equilibrium dynamics of the Markov process models, and counterfactual inference flows from these settings. The proposed approach alleviates the identifiability drawback of the structural causal models, in that the counterfactual inference is consistent with the counterfactual trajectories simulated from the Markov process model.

This manuscript contributes a general and practical framework for casting a Markov process model of a system at equilibrium as a structural causal model, and carrying out counterfactual inference. Markov processes mathematically describe the mechanisms in the system, and predict the system's equilibrium behavior upon intervention, but do not support counterfactual inference. In contrast, structural causal models support counterfactual inference, but do not identify the mechanisms. We define the structural causal models in terms of the parameters and the equilibrium dynamics of the Markov process models, and counterfactual inference flows from these settings. The proposed approach alleviates the identifiability drawback of the structural causal models, in that the counterfactual inference is consistent with the counterfactual trajectories simulated from the Markov process model. We illustrate that, in presence of Markov process model misspecification, counterfactual inference leverages prior data, and therefore estimates the outcome of an intervention more accurately than a direct simulation.

This manuscript contributes a general and practical framework for casting a Markov process model of a system at equilibrium as a structural causal model, and carrying out counterfactual inference. Markov processes mathematically describe the mechanisms in the system, and predict the system's equilibrium behavior upon intervention, but do not support counterfactual inference. In contrast, structural causal models support counterfactual inference, but do not identify the mechanisms. This manuscript leverages the benefits of both approaches. We define the structural causal models in terms of the parameters and the equilibrium dynamics of the Markov process models, and counterfactual inference flows from these settings. The proposed approach alleviates the identifiability drawback of the structural causal models, in that the counterfactual inference is consistent with the counterfactual trajectories simulated from the Markov process model. We showcase the benefits of this framework in case studies of complex biomolecular systems with nonlinear dynamics. We illustrate that, in presence of Markov process model misspecification, counterfactual inference leverages prior data, and therefore estimates the outcome of an intervention more accurately than a direct simulation.