Modern RNA sequencing technologies provide gene expression measurements from single cells that promise refined insights on regulatory relationships among genes. Directed graphical models are well-suited to explore such (cause-effect) relationships. However, statistical analyses of single cell data are complicated by the fact that the data often show zero-inflated expression patterns. To address this challenge, we propose directed graphical models that are based on Hurdle conditional distributions parametrized in terms of polynomials in parent variables and their 0/1 indicators of being zero or nonzero. While directed graphs for Gaussian models are only identifiable up to an equivalence class in general, we show that, under a natural and weak assumption, the exact directed acyclic graph of our zero-inflated models can be identified. We propose methods for graph recovery, apply our model to real single-cell RNA-seq data on T helper cells, and show simulated experiments that validate the identifiability and graph estimation methods in practice.
We introduce a new family of graphical models that consists of graphs with possibly directed, undirected and bidirected edges but without directed cycles. We show that these models are suitable for representing causal models with additive error terms. We provide a set of sufficient graphical criteria for the identification of arbitrary causal effects when the new models contain directed and undirected edges but no bidirected edge. We also provide a necessary and sufficient graphical criterion for the identification of the causal effect of a single variable on the rest of the variables. Moreove…
Covariate adjustment is a commonly used method for total causal effect estimation. In recent years, graphical criteria have been developed to identify all valid adjustment sets, that is, all covariate sets that can be used for this purpose. Different valid adjustment sets typically provide total effect estimates of varying accuracies. Restricting ourselves to causal linear models, we introduce a graphical criterion to compare the asymptotic variances provided by certain valid adjustment sets. We employ this result to develop two further graphical tools. First, we introduce a simple variance re…
We implement Ananke: an object-oriented Python package for causal inference with graphical models. At the top of our inheritance structure is an easily extensible Graph class that provides an interface to several broadly useful graph-based algorithms and methods for visualization. We use best practices of object-oriented programming to implement subclasses of the Graph superclass that correspond to types of causal graphs that are popular in the current literature. This includes directed acyclic graphs for modeling causally sufficient systems, acyclic directed mixed graphs for modeling unmeasur…
Bulk gene expression experiments relied on aggregations of thousands of cells to measure the average expression in an organism. Advances in microfluidic and droplet sequencing now permit expression profiling in single cells. This study of cell-to-cell variation reveals that individual cells lack detectable expression of transcripts that appear abundant on a population level, giving rise to zero-inflated expression patterns. To infer gene co-regulatory networks from such data, we propose a multivariate Hurdle model. It is comprised of a mixture of singular Gaussian distributions. We employ neig…
University of Illinois at Urbana-Champaign（伊利诺伊大学厄巴纳-香槟分校）；École Polytechnique Fédérale de Lausanne（洛桑联邦理工学院）；Carnegie Mellon University（卡内基梅隆大学）
The main approach to defining equivalence among acyclic directed causal graphical models is based on the conditional independence relationships in the distributions that the causal models can generate, in terms of the Markov equivalence. However, it is known that when cycles are allowed in the causal structure, conditional independence may not be a suitable notion for equivalence of two structures, as it does not reflect all the information in the distribution that is useful for identification of the underlying structure. In this paper, we present a general, unified notion of equivalence for l…
We present a graphical approach to deriving inequality constraints for directed acyclic graph (DAG) models, where some variables are unobserved. In particular we show that the observed distribution of a discrete model is always restricted if any two observed variables are neither adjacent in the graph, nor share a latent parent; this generalizes the well known instrumental inequality. The method also provides inequalities on interventional distributions, which can be used to bound causal effects. All these constraints are characterized in terms of a new graphical separation criterion, providin…
Educational systems have traditionally been evaluated using cross-sectional studies, namely, examining a pretest, posttest, and single intervention. Although this is a popular approach, it does not model valuable information such as confounding variables, feedback to students, and other real-world deviations of studies from ideal conditions. Moreover, learning inherently is a sequential process and should involve a sequence of interventions. In this paper, we propose various experimental and quasi-experimental designs for educational systems and quantify them using the graphical model and dire…
Covariate adjustment is a widely used approach to estimate total causal effects from observational data. Several graphical criteria have been developed in recent years to identify valid covariates for adjustment from graphical causal models. These criteria can handle multiple causes, latent confounding, or partial knowledge of the causal structure; however, their diversity is confusing and some of them are only sufficient, but not necessary. In this paper, we present a criterion that is necessary and sufficient for four different classes of graphical causal models: directed acyclic graphs (DAG…
The paper concerns the problem of predicting the effect of actions or interventions on a system from a combination of (i) statistical data on a set of observed variables, and (ii) qualitative causal knowledge encoded in the form of a directed acyclic graph (DAG). The DAG represents a set of linear equations called Structural Equations Model (SEM), whose coefficients are parameters representing direct causal effects. Reliable quantitative conclusions can only be obtained from the model if the causal effects are uniquely determined by the data. That is, if there exists a unique parametrization f…
We develop terminology and methods for working with maximally oriented partially directed acyclic graphs (maximal PDAGs). Maximal PDAGs arise from imposing restrictions on a Markov equivalence class of directed acyclic graphs, or equivalently on its graphical representation as a completed partially directed acyclic graph (CPDAG), for example when adding background knowledge about certain edge orientations. Although maximal PDAGs often arise in practice, causal methods have been mostly developed for CPDAGs. In this paper, we extend such methodology to maximal PDAGs. In particular, we develop me…
Strong untestable assumptions are almost universal in causal point estimation. In particular settings, bounds can be derived to narrow the possible range of a causal effect. Symbolic bounds apply to all settings that can be depicted using the same directed acyclic graph (DAG) and for the same effect of interest. Although the core of the methodology for deriving symbolic bounds has been previously developed, the means of implementation and computation have been lacking. Our R-package causaloptim aims to solve this usability problem by implementing the method of Sachs et al. (2022a) and providin…
We provide a correction to the expression for scoring Gaussian directed acyclic graphical models derived in Geiger and Heckerman [Ann. Statist. 30 (2002) 1414-1440] and discuss how to evaluate the score efficiently.
Directed acyclic graphical models, or DAG models, are widely used to represent complex causal systems. Since the basic task of learning such a model from data is NP-hard, a standard approach is greedy search over the space of directed acyclic graphs or Markov equivalence classes of directed acyclic graphs. As the space of directed acyclic graphs on $p$ nodes and the associated space of Markov equivalence classes are both much larger than the space of permutations, it is desirable to consider permutation-based greedy searches. Here, we provide the first consistency guarantees, both uniform and …
Williams College（威廉姆斯学院）；Emory University（埃默里大学）；Johns Hopkins University（约翰斯·霍普金斯大学）
Identification theory for causal effects in causal models associated with hidden variable directed acyclic graphs (DAGs) is well studied. However, the corresponding algorithms are underused due to the complexity of estimating the identifying functionals they output. In this work, we bridge the gap between identification and estimation of population-level causal effects involving a single treatment and a single outcome. We derive influence function based estimators that exhibit double robustness for the identified effects in a large class of hidden variable DAGs where the treatment satisfies a …
We investigate probabilistic graphical models that allow for both cycles and latent variables. For this we introduce directed graphs with hyperedges (HEDGes), generalizing and combining both marginalized directed acyclic graphs (mDAGs) that can model latent (dependent) variables, and directed mixed graphs (DMGs) that can model cycles. We define and analyse several different Markov properties that relate the graphical structure of a HEDG with a probability distribution on a corresponding product space over the set of nodes, for example factorization properties, structural equations properties, …
We outline a representation for discrete multivariate distributions in terms of interventional potential functions that are globally normalized. This representation can be used to model the effects of interventions, and the independence properties encoded in this model can be represented as a directed graph that allows cycles. In addition to discussing inference and sampling with this representation, we give an exponential family parametrization that allows parameter estimation to be stated as a convex optimization problem; we also give a convex relaxation of the task of simultaneous parameter…
We provide a selected overview of methodology and theory for estimation and inference on the edge weights in high-dimensional directed and undirected Gaussian graphical models. For undirected graphical models, two main explicit constructions are provided: one based on a global method that maximizes the joint likelihood (the graphical Lasso) and one based on a local (nodewise) method that sequentially applies the Lasso to estimate the neighbourhood of each node. The proposed estimators lead to confidence intervals for edge weights and recovery of the edge structure. We evaluate their empirical …
Microorganisms play a critical role in host health. The advancement of high-throughput sequencing technology provides opportunities for a deeper understanding of microbial interactions. However, due to the limitations of 16S ribosomal RNA sequencing, microbiome data are zero-inflated, and a quantitative comparison of microbial abundances cannot be made across subjects. By leveraging a recent microbiome profiling technique that quantifies 16S ribosomal RNA microbial counts, we propose a novel Bayesian graphical model that incorporates microorganisms' evolutionary history through a phylogenetic …
We consider the problem of jointly estimating multiple related directed acyclic graph (DAG) models based on high-dimensional data from each graph. This problem is motivated by the task of learning gene regulatory networks based on gene expression data from different tissues, developmental stages or disease states. We prove that under certain regularity conditions, the proposed $\ell_0$-penalized maximum likelihood estimator converges in Frobenius norm to the adjacency matrices consistent with the data-generating distributions and has the correct sparsity. In particular, we show that this joint…
Probabilistic graphical models are graphical representations of probability distributions. Graphical models have applications in many fields including biology, social sciences, linguistic, neuroscience. In this paper, we propose directed acyclic graphs (DAGs) learning via bootstrap aggregating. The proposed procedure is named as DAGBag. Specifically, an ensemble of DAGs is first learned based on bootstrap resamples of the data and then an aggregated DAG is derived by minimizing the overall distance to the entire ensemble. A family of metrics based on the structural hamming distance is defined …
Learning the structure of dependence relations between variables is a pervasive issue in the statistical literature. A directed acyclic graph (DAG) can represent a set of conditional independences, but different DAGs may encode the same set of relations and are indistinguishable using observational data. Equivalent DAGs can be collected into classes, each represented by a partially directed graph known as essential graph (EG). Structure learning directly conducted on the EG space, rather than on the allied space of DAGs, leads to theoretical and computational benefits. Still, the majority of e…
Consider the case where cause-effect relationships between variables can be described as a directed acyclic graph and the corresponding linear structural equation model. This paper provides graphical identifiability criteria for total effects by using surrogate variables in the case where it is difficult to observe a treatment/response variable. The results enable us to judge from graph structure whether a total effect can be identified through the observation of surrogate variables.
A graphical model is a statistical model that is associated to a graph whose nodes correspond to variables of interest. The edges of the graph reflect allowed conditional dependencies among the variables. Graphical models admit computationally convenient factorization properties and have long been a valuable tool for tractable modeling of multivariate distributions. More recently, applications such as reconstructing gene regulatory networks from gene expression data have driven major advances in structure learning, that is, estimating the graph underlying a model. We review some of these advan…
In this essay I discuss potential outcome and graphical approaches to causality, and their relevance for empirical work in economics. I review some of the work on directed acyclic graphs, including the recent "The Book of Why," by Pearl and MacKenzie. I also discuss the potential outcome framework developed by Rubin and coauthors, building on work by Neyman. I then discuss the relative merits of these approaches for empirical work in economics, focusing on the questions each answer well, and why much of the the work in economics is closer in spirit to the potential outcome framework.
Marginal log-linear (MLL) models provide a flexible approach to multivariate discrete data. MLL parametrizations under linear constraints induce a wide variety of models, including models defined by conditional independences. We introduce a sub-class of MLL models which correspond to Acyclic Directed Mixed Graphs (ADMGs) under the usual global Markov property. We characterize for precisely which graphs the resulting parametrization is variation independent. The MLL approach provides the first description of ADMG models in terms of a minimal list of constraints. The parametrization is also easi…
Graphical models with bi-directed edges (<->) represent marginal independence: the absence of an edge between two vertices indicates that the corresponding variables are marginally independent. In this paper, we consider maximum likelihood estimation in the case of continuous variables with a Gaussian joint distribution, sometimes termed a covariance graph model. We present a new fitting algorithm which exploits standard regression techniques and establish its convergence properties. Moreover, we contrast our procedure to existing estimation methods.
This paper introduces an estimator of the relative directed distance between an estimated model and the true model, based on the Kulback-Leibler divergence and is motivated by the generalized information criterion proposed by Konishi and Kitagawa. This estimator can be used to select model in penalized Gaussian copula graphical models. The use of this estimator is not feasible for high-dimensional cases. However, we derive an efficient way to compute this estimator which is feasible for the latter class of problems. Moreover, this estimator is, generally, appropriate for several penalties such…
We introduce the concept of pattern graphs--directed acyclic graphs representing how response patterns are associated. A pattern graph represents an identifying restriction that is nonparametrically identified/saturated and is often a missing not at random restriction. We introduce a selection model and a pattern mixture model formulations using the pattern graphs and show that they are equivalent. A pattern graph leads to an inverse probability weighting estimator as well as an imputation-based estimator. We also study the semi-parametric efficiency theory and derive a multiply-robust estimat…
Graphical models are popular statistical tools which are used to represent dependent or causal complex systems. Statistically equivalent causal or directed graphical models are said to belong to a Markov equivalent class. It is of great interest to describe and understand the space of such classes. However, with currently known algorithms, sampling over such classes is only feasible for graphs with fewer than approximately 20 vertices. In this paper, we design reversible irreducible Markov chains on the space of Markov equivalent classes by proposing a perfect set of operators that determine t…
We study efficient estimation of an interventional mean associated with a point exposure treatment under a causal graphical model represented by a directed acyclic graph without hidden variables. Under such a model, it may happen that a subset of the variables are uninformative in that failure to measure them neither precludes identification of the interventional mean nor changes the semiparametric variance bound for regular estimators of it. We develop a set of graphical criteria that are sound and complete for eliminating all the uninformative variables so that the cost of measuring them can…
Missing data has the potential to affect analyses conducted in all fields of scientific study, including healthcare, economics, and the social sciences. Several approaches to unbiased inference in the presence of non-ignorable missingness rely on the specification of the target distribution and its missingness process as a probability distribution that factorizes with respect to a directed acyclic graph. In this paper, we address the longstanding question of the characterization of models that are identifiable within this class of missing data distributions. We provide the first completeness r…
Graphical Markov models combine conditional independence constraints with graphical representations of stepwise data generating processes.The models started to be formulated about 40 years ago and vigorous development is ongoing. Longitudinal observational studies as well as intervention studies are best modeled via a subclass called regression graph models and, especially traceable regressions. Regression graphs include two types of undirected graph and directed acyclic graphs in ordered sequences of joint responses. Response components may correspond to discrete or continuous random variable…
University of Washington（华盛顿大学）；Technical University of Munich（慕尼黑工业大学）
In causal graphical models based on directed acyclic graphs (DAGs), directed paths represent causal pathways between the corresponding variables. The variable at the beginning of such a path is referred to as an ancestor of the variable at the end of the path. Ancestral relations between variables play an important role in causal modeling. In existing literature on structure learning, these relations are usually deduced from learned structures and used for orienting edges or formulating constraints of the space of possible DAGs. However, they are usually not posed as immediate target of infere…
CIRAD（法国农业研究与国际合作组织）；Inria（法国国家信息与自动化研究所）；Univ. Grenoble Alpes（格勒诺布尔阿尔卑斯大学）；Laboratoire Jean Kuntzmann（让·库茨曼实验室）
Multivariate count data are defined as the number of items of different categories issued from sampling within a population, which individuals are grouped into categories. The analysis of multivariate count data is a recurrent and crucial issue in numerous modelling problems, particularly in the fields of biology and ecology (where the data can represent, for example, children counts associated with multitype branching processes), sociology and econometrics. We focus on I) Identifying categories that appear simultaneously, or on the contrary that are mutually exclusive. This is achieved by ide…
Directed acyclic graphs (DAGs) are commonly used to represent causal relationships among random variables in graphical models. Applications of these models arise in the study of physical, as well as biological systems, where directed edges between nodes represent the influence of components of the system on each other. The general problem of estimating DAGs from observed data is computationally NP-hard, Moreover two directed graphs may be observationally equivalent. When the nodes exhibit a natural ordering, the problem of estimating directed graphs reduces to the problem of estimating the str…
