Copula Adapted Directed Acyclic Graph for Cluster Representation of Biomedical Data

In complex multivariate systems, interactions among variables are defined by dependency structures, often encoded as directed acyclic graphs ($\text{DAGs}$). However, dependency structures can vary across subjects, and ignoring this structural heterogeneity introduces bias and obscures subpopulation-specific dependencies. To address this, we propose Directed Acyclic Graph-based Dependency Clustering via Alternating Direction Method of Multipliers (DAG-DC-ADMM), a unified framework built upon Structural Equation Modeling (SEM) that jointly learns cluster assignments and cluster-specific dependency structures. We encode acyclicity via a smooth constraint and integrate a groupwise truncated Lasso fusion penalty (gTLP) to cluster subjects based on their structural similarity. This yields a nonconvex optimization problem that incorporates sparsity, acyclicity, and structural consensus constraints. We address the nonconvexity by using the augmented Lagrangian method and solve it with an adapted version of the Alternating Direction Method of Multipliers (ADMM) for difference-of-convex programs. For certain graph structures, such as upper triangular adjacency matrices, our algorithm is guaranteed to converge to a Karush-Kuhn-Tucker (KKT) point. Experiments demonstrate that our method recovers cluster-specific causal dependency structures with a high true positive rate and a low false discovery rate. This capability enables the robust discovery of heterogeneous dependencies across subjects where the subpopulation label is unknown.

Recent algorithmic advances have made directed acyclic graph (DAG) structure learning scalable for causal discovery. Yet, the currently available techniques assume a completely homogeneous population, precluding their application to clustered data where cluster-specific variations (e.g., patient-specific effects) are common. We address this issue by introducing a new approach that estimates a global structure while accounting for local cluster-level effects. The key idea is to extend the fixed- and random-effects framework of classical mixed models to the structure learning setting. Towards this end, we present a differentiable graph coupling mechanism that guarantees the union of the fixed- and random-effects graphs remains acyclic. Computationally, we provide a provably convergent first-order method and leverage efficient batched updates across clusters. Statistically, we establish identifiability of the model and show that our approach recovers the true structure asymptotically. In experiments on real and synthetic data, our proposal detects dependencies missed by alternative estimators, underscoring its value for structure learning in clustered settings.

Constructing causal directed acyclic graphs (DAGs) is a core step in biomedical causal analysis, yet it remains a largely manual process. Analysts must connect study variables to prior literature, evaluate uncertain causal claims, and preserve sufficient provenance for expert review. We present EviDAG, a browser-based system for authoring causal DAGs as auditable, evidence-linked artifacts from biomedical literature. Given free-text descriptions of study concepts, EviDAG creates a reproducible literature snapshot, uses an LLM-based reasoning module to generate structured pairwise causal judgments, links literature-supported judgments to verbatim evidence excerpts, and assembles the judgments into a constraint-checked graph. Each proposed edge includes confidence estimates, provenance, and a reviewable rationale. The interface supports study specification, progress monitoring, evidence review, graph comparison, adjustment-set computation, and export. In evaluations against both compact benchmark DAGs and reference DAGs derived from published literature, EviDAG achieves high edge recall on the literature-based cohort while retaining verifiable evidence trails absent from LLM-only baselines. EviDAG thus reduces the burden of causal DAG curation while making the resulting assumptions auditable, supporting the design, analysis, and interpretation of biomedical studies.