Causal Discovery with Fewer Conditional Independence Tests

Many questions in science center around the fundamental problem of understanding causal relationships. However, most constraint-based causal discovery algorithms, including the well-celebrated PC algorithm, often incur an exponential number of conditional independence (CI) tests, posing limitations in various applications. Addressing this, our work focuses on characterizing what can be learned about the underlying causal graph with a reduced number of CI tests. We show that it is possible to a learn a coarser representation of the hidden causal graph with a polynomial number of tests. This coarser representation, named Causal Consistent Partition Graph (CCPG), comprises of a partition of the vertices and a directed graph defined over its components. CCPG satisfies consistency of orientations and additional constraints which favor finer partitions. Furthermore, it reduces to the underlying causal graph when the causal graph is identifiable. As a consequence, our results offer the first efficient algorithm for recovering the true causal graph with a polynomial number of tests, in special cases where the causal graph is fully identifiable through observational data and potentially additional interventions.

Synthetic Potential Outcomes for Mixtures of Treatment Effects

Modern data analysis frequently relies on the use of large datasets, often constructed as amalgamations of diverse populations or data-sources. Heterogeneity across these smaller datasets constitutes two major challenges for causal inference: (1) the source of each sample can introduce latent confounding between treatment and effect, and (2) diverse populations may respond differently to the same treatment, giving rise to heterogeneous treatment effects (HTEs). The issues of latent confounding and HTEs have been studied separately but not in conjunction. In particular, previous works only report the conditional average treatment effect (CATE) among similar individuals (with respect to the measured covariates). CATEs cannot resolve mixtures of potential treatment effects driven by latent heterogeneity, which we call mixtures of treatment effects (MTEs). Inspired by method of moment approaches to mixture models, we propose "synthetic potential outcomes" (SPOs). Our new approach deconfounds heterogeneity while also guaranteeing the identifiability of MTEs. This technique bypasses full recovery of a mixture, which significantly simplifies its requirements for identifiability. We demonstrate the efficacy of SPOs on synthetic data.

Season combinatorial intervention predictions with Salt & Peper

Interventions play a pivotal role in the study of complex biological systems. In drug discovery, genetic interventions (such as CRISPR base editing) have become central to both identifying potential therapeutic targets and understanding a drug's mechanism of action. With the advancement of CRISPR and the proliferation of genome-scale analyses such as transcriptomics, a new challenge is to navigate the vast combinatorial space of concurrent genetic interventions. Addressing this, our work concentrates on estimating the effects of pairwise genetic combinations on the cellular transcriptome. We introduce two novel contributions: Salt, a biologically-inspired baseline that posits the mostly additive nature of combination effects, and Peper, a deep learning model that extends Salt's additive assumption to achieve unprecedented accuracy. Our comprehensive comparison against existing state-of-the-art methods, grounded in diverse metrics, and our out-of-distribution analysis highlight the limitations of current models in realistic settings. This analysis underscores the necessity for improved modelling techniques and data acquisition strategies, paving the way for more effective exploration of genetic intervention effects.

Membership Testing in Markov Equivalence Classes via Independence Query Oracles

Understanding causal relationships between variables is a fundamental problem with broad impact in numerous scientific fields. While extensive research has been dedicated to learning causal graphs from data, its complementary concept of testing causal relationships has remained largely unexplored. While learning involves the task of recovering the Markov equivalence class (MEC) of the underlying causal graph from observational data, the testing counterpart addresses the following critical question: Given a specific MEC and observational data from some causal graph, can we determine if the data-generating causal graph belongs to the given MEC? We explore constraint-based testing methods by establishing bounds on the required number of conditional independence tests. Our bounds are in terms of the size of the maximum undirected clique ($s$) of the given MEC. In the worst case, we show a lower bound of $\exp(\Omega(s))$ independence tests. We then give an algorithm that resolves the task with $\exp(O(s))$ tests, matching our lower bound. Compared to the learning problem, where algorithms often use a number of independence tests that is exponential in the maximum in-degree, this shows that testing is relatively easier. In particular, it requires exponentially less independence tests in graphs featuring high in-degrees and small clique sizes. Additionally, using the DAG associahedron, we provide a geometric interpretation of testing versus learning and discuss how our testing result can aid learning.

Causal Imputation for Counterfactual SCMs: Bridging Graphs and Latent Factor Models

We consider the task of causal imputation, where we aim to predict the outcomes of some set of actions across a wide range of possible contexts. As a running example, we consider predicting how different drugs affect cells from different cell types. We study the index-only setting, where the actions and contexts are categorical variables with a finite number of possible values. Even in this simple setting, a practical challenge arises, since often only a small subset of possible action-context pairs have been studied. Thus, models must extrapolate to novel action-context pairs, which can be framed as a form of matrix completion with rows indexed by actions, columns indexed by contexts, and matrix entries corresponding to outcomes. We introduce a novel SCM-based model class, where the outcome is expressed as a counterfactual, actions are expressed as interventions on an instrumental variable, and contexts are defined based on the initial state of the system. We show that, under a linearity assumption, this setup induces a latent factor model over the matrix of outcomes, with an additional fixed effect term. To perform causal prediction based on this model class, we introduce simple extension to the Synthetic Interventions estimator (Agarwal et al., 2020). We evaluate several matrix completion approaches on the PRISM drug repurposing dataset, showing that our method outperforms all other considered matrix completion approaches.

Causal Discovery under Off-Target Interventions

Causal graph discovery is a significant problem with applications across various disciplines. However, with observational data alone, the underlying causal graph can only be recovered up to its Markov equivalence class, and further assumptions or interventions are necessary to narrow down the true graph. This work addresses the causal discovery problem under the setting of stochastic interventions with the natural goal of minimizing the number of interventions performed. We propose the following stochastic intervention model which subsumes existing adaptive noiseless interventions in the literature while capturing scenarios such as fat-hand interventions and CRISPR gene knockouts: any intervention attempt results in an actual intervention on a random subset of vertices, drawn from a distribution dependent on attempted action. Under this model, we study the two fundamental problems in causal discovery of verification and search and provide approximation algorithms with polylogarithmic competitive ratios and provide some preliminary experimental results.

Removing Biases from Molecular Representations via Information Maximization

High-throughput drug screening -- using cell imaging or gene expression measurements as readouts of drug effect -- is a critical tool in biotechnology to assess and understand the relationship between the chemical structure and biological activity of a drug. Since large-scale screens have to be divided into multiple experiments, a key difficulty is dealing with batch effects, which can introduce systematic errors and non-biological associations in the data. We propose InfoCORE, an Information maximization approach for COnfounder REmoval, to effectively deal with batch effects and obtain refined molecular representations. InfoCORE establishes a variational lower bound on the conditional mutual information of the latent representations given a batch identifier. It adaptively reweighs samples to equalize their implied batch distribution. Extensive experiments on drug screening data reveal InfoCORE's superior performance in a multitude of tasks including molecular property prediction and molecule-phenotype retrieval. Additionally, we show results for how InfoCORE offers a versatile framework and resolves general distribution shifts and issues of data fairness by minimizing correlation with spurious features or removing sensitive attributes. The code is available at https://github.com/uhlerlab/InfoCORE.

Meek Separators and Their Applications in Targeted Causal Discovery

Learning causal structures from interventional data is a fundamental problem with broad applications across various fields. While many previous works have focused on recovering the entire causal graph, in practice, there are scenarios where learning only part of the causal graph suffices. This is called $targeted$ causal discovery. In our work, we focus on two such well-motivated problems: subset search and causal matching. We aim to minimize the number of interventions in both cases. Towards this, we introduce the $Meek~separator$, which is a subset of vertices that, when intervened, decomposes the remaining unoriented edges into smaller connected components. We then present an efficient algorithm to find Meek separators that are of small sizes. Such a procedure is helpful in designing various divide-and-conquer-based approaches. In particular, we propose two randomized algorithms that achieve logarithmic approximation for subset search and causal matching, respectively. Our results provide the first known average-case provable guarantees for both problems. We believe that this opens up possibilities to design near-optimal methods for many other targeted causal structure learning problems arising from various applications.

Identifiability Guarantees for Causal Disentanglement from Soft Interventions

Causal disentanglement aims to uncover a representation of data using latent variables that are interrelated through a causal model. Such a representation is identifiable if the latent model that explains the data is unique. In this paper, we focus on the scenario where unpaired observational and interventional data are available, with each intervention changing the mechanism of a latent variable. When the causal variables are fully observed, statistically consistent algorithms have been developed to identify the causal model under faithfulness assumptions. We here show that identifiability can still be achieved with unobserved causal variables, given a generalized notion of faithfulness. Our results guarantee that we can recover the latent causal model up to an equivalence class and predict the effect of unseen combinations of interventions, in the limit of infinite data. We implement our causal disentanglement framework by developing an autoencoding variational Bayes algorithm and apply it to the problem of predicting combinatorial perturbation effects in genomics.

Unpaired Multi-Domain Causal Representation Learning

The goal of causal representation learning is to find a representation of data that consists of causally related latent variables. We consider a setup where one has access to data from multiple domains that potentially share a causal representation. Crucially, observations in different domains are assumed to be unpaired, that is, we only observe the marginal distribution in each domain but not their joint distribution. In this paper, we give sufficient conditions for identifiability of the joint distribution and the shared causal graph in a linear setup. Identifiability holds if we can uniquely recover the joint distribution and the shared causal representation from the marginal distributions in each domain. We transform our identifiability results into a practical method to recover the shared latent causal graph. Moreover, we study how multiple domains reduce errors in falsely detecting shared causal variables in the finite data setting.