Large-Scale Bayesian Causal Discovery with Interventional Data

Inferring the causal relationships among a set of variables in the form of a directed acyclic graph (DAG) is an important but notoriously challenging problem. Recently, advancements in high-throughput genomic perturbation screens have inspired development of methods that leverage interventional data to improve model identification. However, existing methods still suffer poor performance on large-scale tasks and fail to quantify uncertainty. Here, we propose Interventional Bayesian Causal Discovery (IBCD), an empirical Bayesian framework for causal discovery with interventional data. Our approach models the likelihood of the matrix of total causal effects, which can be approximated by a matrix normal distribution, rather than the full data matrix. We place a spike-and-slab horseshoe prior on the edges and separately learn data-driven weights for scale-free and ErdHos-R'enyi structures from observational data, treating each edge as a latent variable to enable uncertainty-aware inference. Through extensive simulation, we show that IBCD achieves superior structure recovery compared to existing baselines. We apply IBCD to CRISPR perturbation (Perturb-seq) data on 521 genes, demonstrating that edge posterior inclusion probabilities enable identification of robust graph structures.