Heterogeneous data from multiple populations, sub-groups, or sources can be represented as a "mixture model" with a single latent class influencing all of the observed covariates. Heterogeneity can be resolved at different levels by grouping populations according to different notions of similarity. This paper proposes grouping with respect to the causal response of an intervention or perturbation on the system. This is distinct from previous notions, such as grouping by similar covariate values (e.g., clustering) or similar correlations between covariates (e.g., Gaussian mixture models). To solve the problem, we "synthetically sample" from a counterfactual distribution using higher-order multi-linear moments of the observable data. To understand how these “causal mixtures” fit in with more classical notions, we develop a hierarchy of mixture identifiability.

Causal disentanglement seeks a representation of data involving latent variables that are related via a causal model. A representation is identifiable if both the latent model and the transformation from latent to observed variables are unique. In this paper, we study observed variables that are a linear transformation of a linear latent causal model. Data from interventions are necessary for identifiability: if one latent variable is missing an intervention, we show that there exist distinct models that cannot be distinguished. Conversely, we show that a single intervention on each latent variable is sufficient for identifiability. Our proof uses a generalization of the RQ decomposition of a matrix that replaces the usual orthogonal and upper triangular conditions with analogues depending on a partial order on the rows of the matrix, with partial order determined by a latent causal model. We corroborate our theoretical results with a method for causal disentanglement. We show that the method accurately recovers a latent causal model on synthetic and semi-synthetic data and we illustrate a use case on a dataset of single-cell RNA sequencing measurements.

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 results into a practical method to recover the shared latent causal graph.

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.

Transforming a causal system from a given initial state to a desired target state is an important task permeating multiple fields including control theory, biology, and materials science. In causal models, such transformations can be achieved by performing a set of interventions. In this paper, we consider the problem of identifying a shift intervention that matches the desired mean of a system through active learning. We define the Markov equivalence class that is identifiable from shift interventions and propose two active learning strategies that are guaranteed to exactly match a desired mean. We then derive a worst-case lower bound for the number of interventions required and show that these strategies are optimal for certain classes of graphs. In particular, we show that our strategies may require exponentially fewer interventions than the previously considered approaches, which optimize for structure learning in the underlying causal graph. In line with our theoretical results, we also demonstrate experimentally that our proposed active learning strategies require fewer interventions compared to several baselines.

SUMMARY: Designing interventions to control gene regulation necessitates modeling a gene regulatory network by a causal graph. Currently, large-scale gene expression datasets from different conditions, cell types, disease states, and developmental time points are being collected. However, application of classical causal inference algorithms to infer gene regulatory networks based on such data is still challenging, requiring high sample sizes and computational resources. Here, we describe an algorithm that efficiently learns the differences in gene regulatory mechanisms between different conditions. Our difference causal inference (DCI) algorithm infers changes (i.e. edges that appeared, disappeared, or changed weight) between two causal graphs given gene expression data from the two conditions. This algorithm is efficient in its use of samples and computation since it infers the differences between causal graphs directly without estimating each possibly large causal graph separately. We provide a user-friendly Python implementation of DCI and also enable the user to learn the most robust difference causal graph across different tuning parameters via stability selection. Finally, we show how to apply DCI to single-cell RNA-seq data from different conditions and cell states, and we also validate our algorithm by predicting the effects of interventions. AVAILABILITY AND IMPLEMENTATION: Python package freely available at http://uhlerlab.github.io/causaldag/dci. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

We consider the task of learning a causal graph in the presence of latent confounders given i.i.d.samples from the model. While current algorithms for causal structure discovery in the presence of latent confounders are constraint-based, we here propose a hybrid approach. We prove that under assumptions weaker than faithfulness, any sparsest independence map (IMAP) of the distribution belongs to the Markov equivalence class of the true model. This motivates the Sparsest Poset formulation - that posets can be mapped to minimal IMAPs of the true model such that the sparsest of these IMAPs is Markov equivalent to the true model. Motivated by this result, we propose a greedy algorithm over the space of posets for causal structure discovery in the presence of latent confounders and compare its performance to the current state-of-the-art algorithms FCI and FCI+ on synthetic data.

A growing body of work has begun to study intervention design for efficient structure learning of causal directed acyclic graphs (DAGs). A typical setting is a \emph{causally sufficient} setting, i.e. a system with no latent confounders, selection bias, or feedback, when the essential graph of the observational equivalence class (EC) is given as an input and interventions are assumed to be noiseless. Most existing works focus on \textit{worst-case} or \textit{average-case} lower bounds for the number of interventions required to orient a DAG. These worst-case lower bounds only establish that the largest clique in the essential graph \textit{could} make it difficult to learn the true DAG. In this work, we develop a \textit{universal} lower bound for single-node interventions that establishes that the largest clique is \textit{always} a fundamental impediment to structure learning. Specifically, we present a decomposition of a DAG into independently orientable components through \emph{directed clique trees} and use it to prove that the number of single-node interventions necessary to orient any DAG in an EC is at least the sum of half the size of the largest cliques in each chain component of the essential graph. Moreover, we present a two-phase intervention design algorithm that, under certain conditions on the chordal skeleton, matches the optimal number of interventions up to a multiplicative logarithmic factor in the number of maximal cliques. We show via synthetic experiments that our algorithm can scale to much larger graphs than most of the related work and achieves better worst-case performance than other scalable approaches. A code base to recreate these results can be found at \url{https://github.com/csquires/dct-policy}.

We consider the problem of estimating causal DAG models from a mix of observational and interventional data, when the intervention targets are partially or completely unknown. This problem is highly relevant for example in genomics, since gene knockout technologies are known to have off-target effects. We characterize the interventional Markov equivalence class of DAGs that can be identified from interventional data with unknown intervention targets. In addition, we propose a provably consistent algorithm for learning the interventional Markov equivalence class from such data. The proposed algorithm greedily searches over the space of permutations to minimize a novel score function. The algorithm is nonparametric, which is particularly important for applications to genomics, where the relationships between variables are often non-linear and the distribution non-Gaussian. We demonstrate the performance of our algorithm on synthetic and biological datasets. Links to an implementation of our algorithm and to a reproducible code base for our experiments can be found at https://uhlerlab.github.io/causaldag/utigsp.

Determining the causal structure of a set of variables is critical for both scientific inquiry and decision-making. However, this is often challenging in practice due to limited interventional data. Given that randomized experiments are usually expensive to perform, we propose a general framework and theory based on optimal Bayesian experimental design to select experiments for targeted causal discovery. That is, we assume the experimenter is interested in learning some function of the unknown graph (e.g., all descendants of a target node) subject to design constraints such as limits on the number of samples and rounds of experimentation. While it is in general computationally intractable to select an optimal experimental design strategy, we provide a tractable implementation with provable guarantees on both approximation and optimization quality based on submodularity. We evaluate the efficacy of our proposed method on both synthetic and real datasets, thereby demonstrating that our method realizes considerable performance gains over baseline strategies such as random sampling.

Directed acyclic graph (DAG) models are popular for capturing causal relationships. From observational and interventional data, a DAG model can only be determined up to its \emph{interventional Markov equivalence class} (I-MEC). We investigate the size of MECs for random DAG models generated by uniformly sampling and ordering an Erdős-Rényi graph. For constant density, we show that the expected $\log$ observational MEC size asymptotically (in the number of vertices) approaches a constant. We characterize I-MEC size in a similar fashion in the above settings with high precision. We show that the asymptotic expected number of interventions required to fully identify a DAG is a constant. These results are obtained by exploiting Meek rules and coupling arguments to provide sharp upper and lower bounds on the asymptotic quantities, which are then calculated numerically up to high precision. Our results have important consequences for experimental design of interventions and the development of algorithms for causal inference.

We consider the problem of estimating the differences between two causal directed acyclic graph (DAG) models with a shared topological order given i.i.d. samples from each model. This is of interest for example in genomics, where changes in the structure or edge weights of the underlying causal graphs reflect alterations in the gene regulatory networks. We here provide the first provably consistent method for directly estimating the differences in a pair of causal DAGs without separately learning two possibly large and dense DAG models and computing their difference. Our two-step algorithm first uses invariance tests between regression coefficients of the two data sets to estimate the skeleton of the difference graph and then orients some of the edges using invariance tests between regression residual variances. We demonstrate the properties of our method through a simulation study and apply it to the analysis of gene expression data from ovarian cancer and during T-cell activation.