Directed acyclic graphs (DAGs) constitute a central modeling tool to enable principled reasoning about cause-effect interactions in complex systems. However, since the causal structure underlying a group of variables is often unknown and interventions may be infeasible or ethically challenging to implement, there is a need to address the task of inferring DAGs from observational data. However, most classical structure identification approaches face two key obstacles: the combinatorial challenge of enforcing acyclicity, which severely limits scalability, and identifiability challenges arising from latent confounding or heterogeneous noise. This tutorial offers an overview of recent signal processing and optimization advances that address these issues by recasting DAG structure learning as a continuous, score-based estimation problem over adjacency matrices. We begin with a didactic introduction to structural equation models and the formulation of causal graph recovery, followed by a historical survey of score-based methods ranging from early combinatorial search schemes and greedy heuristics to modern continuous frameworks that leverage smooth characterizations of acyclicity. Building on this foundation, we describe concomitant DAG estimation methods that jointly infer sparse causal structure and exogenous noise levels, improving robustness under heteroscedasticity and distribution shifts by rendering the estimator noise adaptive. All in all, the tutorial introduces readers to challenges and opportunities for signal processing research at the crossroads of causal inference, high-dimensional statistics, and scalable graph learning, while outlining emerging directions including online, nonlinear, and neural causal discovery.

Protein-protein interactions (PPIs) govern nearly all cellular processes, yet computational methods for identifying binding partners typically produce ranked predictions without mechanistic justification. This creates a fundamental barrier to adoption because biologists cannot assess whether predictions reflect genuine biochemical insight or spurious correlations. We present \textbf{Protein Thoughts}, a framework that reformulates PPI discovery as an interpretable search problem with explicit reasoning. The system decomposes binding evidence into four biologically meaningful signals: sequence similarity reflecting evolutionary relationships, structural complementarity capturing geometric fit, interface balance, and chemical compatibility encoding residue-level interactions. Rather than collapsing these signals into an opaque score, we preserve their individual contributions through a transparent value function that enables both ranking and auditing. To navigate large candidate spaces efficiently, we introduce hypothesis-guided entropy-regularized Tree-of-Thoughts search. A fine-tuned language model generates search directives from embedding-derived features, classifying candidates as high-priority, exploratory, or skippable. These directives condition a Boltzmann policy that balances exploitation with entropy-driven exploration, while hypothesis-aware pruning prevents premature abandonment of promising candidates. For candidates exhibiting score disagreement, hypothesis-conditioned embedding-space flow matching transports protein embeddings toward the binder manifold. On the SHS148k benchmark, Protein Thoughts achieves mean best-binder rank of 11.2 versus 47.7 for an entropic tree search baseline, a 76% improvement, and for binding prediction the trained value function achieves $91.08 \pm 0.19$ Micro-F1, outperforming existing PPI methods on the same dataset.

A natural assumption is that if each model is individually calibrated, the aggregate prediction will also be well calibrated. We show that this assumption fails in multi-agent settings: individually calibrated predictors can become collectively miscalibrated when their predictions interact strategically--where "strategically" refers to the game-theoretic sense of Brier-optimal local response, not deliberate gaming or collusion, and arises naturally whenever agents are independently trained on overlapping data. This phenomenon affects multiple independent agents in federated healthcare, multi-vendor intrusion detection, and crowdsourced forecasting, where agents optimize their own objectives. Specifically, we prove that under Brier-score-based aggregation with positively correlated beliefs each agent's individually optimal report systematically underestimates the positive-class probability, yielding a Price of Anarchy strictly greater than one whenever Cov(bi,bj) > 0. At our canonical setting (n=5 agents, pairwise correlation ρ=0.5, base rate µ=0.3, threshold τ=0.3) the empirically measured PoA in false-negative rate is 7.25 (mean aggregate bias 0.375). In contrast, VCG-based aggregation, which rewards each agent's marginal contribution to aggregate accuracy, achieves dominant-strategy incentive compatibility and the lowest empirical PoA among all mechanisms studied (PoA 1.0). On three real-world datasets (NSL-KDD, UNSW-NB15, Credit Card Fraud) with featurepartitioned agents, VCG provides the strongest robustness guarantees among the aggregation methods we evaluate, while maintaining comparable accuracy. In data-sparse regimes (n 500), VCG consistently outperforms stacking and majority voting; under adversarial agents, VCG maintains substantially lower false-negative rates than robust aggregation baselines. Adaptive weight updates further reduce false negatives by 20-22% under distribution shift, with O( T) online regret guarantees. These results establish that how probabilistic predictions are aggregated matters as much as how well individual models are calibrated.

Many clinical risk scores are deployed as additive rules with nonnegative integer points assigned to relevant binary predictive features. These integer weights not only make the score easier to use in practice but also promote sparsity in the resulting prediction model. Such risk scores are often derived by first fitting a regression model and then rounding the estimated coefficients to the nearest integer after appropriate scaling. This approach is computationally fast but does not guarantee optimality of the resulting score. Alternatively, one may search over all possible integer weights to directly optimize a value function by posing the problem as an integer programming task. However, the associated computational burden can be substantial, especially when the value function is nonconcave or even discontinuous. In this paper, we develop new machine learning algorithms that employ a flexible greedy optimization strategy to learn such additive scoring directly under explicit and sensible optimality objectives. We apply the proposed method to a large electronic health record (EHR) cohort in Epic Cosmos to construct an integer-weighted comorbidity score for measuring the risk of post-discharge mortality. We also conduct a simulation study to examine the finite-sample operating characteristics.

Tensor-valued data arise naturally in neuroimaging, genomics, climate science, and spatiotemporal networks, where multilinear dependencies across modes carry information that is destroyed under vectorization. Existing approaches either impose a single low-rank structure, which can miss localized signal, or treat the tensor as a long vector, which discards its multiway geometry. We propose a *Dual-Channel Tensor Neural Network* (DC-TNN) that decomposes each tensor input into a low-rank core and a sparse refinement, and processes the two components through coupled neural channels. The framework is structure-agnostic and accommodates CP, Tucker, and tensor-train cores within a single architecture. For estimation, we establish non-asymptotic risk bounds for the DC-TNN estimator that decompose into network approximation, core estimation, and refinement-selection terms, and show that the effective dimension is determined jointly by the core rank and refinement sparsity rather than by the ambient tensor size. For inference, we develop a *structure-aware conformal ROC* procedure that calibrates within the core-refinement latent space and produces ROC and AUC confidence bands with finite-sample, distribution-free coverage. Building on this, we propose a *conformal structure selector* that, to our knowledge, is the *first distribution-free procedure* for choosing among candidate tensor decompositions with finite-sample validity. Simulations and an analysis of a protein dataset demonstrate competitive predictive accuracy, reliable uncertainty quantification, and consistent recovery of the tensor structure.

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.

Decision-makers frequently must choose a single action from a finite set of alternatives -- for example, physicians selecting a treatment, investors choosing a portfolio risk level, or judges determining sentences. To improve outcomes, policymakers often issue policy rules or guidelines to inform such choices. In this paper, I show how to generally derive policy rules from observational data in a multi-action framework under relatively weak assumptions about the underlying structure of the heterogeneous sampled population. Conditional average treatment effects (CATEs) are consistently estimated via a weighted K-means algorithm, assuming the outcome model is correctly specified within each homogeneous subgroup. Feasible policy rules are then implemented via a standard decision tree, allowing for both perfect and imperfect adherence to treatment. The methodology is applied to treatment options for Hepatitis C (HCV) among patients co-infected with human immunodeficiency virus (HIV), a setting in which no uniform guideline exists for modern pharmaceutical therapies. The results identify a subgroup of patients with approximately an 80% probability of spontaneous HCV clearance without treatment. Estimation results also show that reallocating treatments among treated individuals could have reduced total treatment costs by CAN$3.6-4.9 million while still increasing aggregate health benefits relative to the status quo. These findings demonstrate that the proposed approach can generate improved, data-driven treatment guidelines for the management of HIV/HCV co-infected patients.

Differentiable optimization layers are traditionally integrated in predict-then-optimize frameworks where a neural model estimates parameters that subsequently serve as fixed inputs to downstream decision-making optimization problems. In this work, we introduce the concept of a "fairness layer": a differentiable optimization layer appended to a model's output layer that guarantees a chosen notion of output parity is satisfied when integrated into a neural network. Additionally, we introduce an online primal-dual inference algorithm that provides provable aggregate fairness guarantees for streaming predictions with arbitrarily small batch sizes, where traditional per-batch constraints become overly restrictive. Numerical experiments demonstrate the effectiveness of the fairness layer and associated algorithm, and theoretical analysis characterizes the layer's differentiability and stability properties during model training and backpropagation. Our code for these experiments is publicly available on GitHub (https://github.com/dtroxell19/FairDL-ICML-2026.git) and our public Python package documentation can be found online: https://dtroxell19.github.io/fairness_training/.

The functional ANOVA, or Hoeffding decomposition, provides a principled framework for interpretability by decomposing a model prediction into main effects and higher-order interactions. For independent inputs, this classical decomposition is explicit. It is closely connected to SHAP values, generalized additive models, and orthogonal polynomial expansions, and therefore constitutes a fundamental tool for additive explainability. In the more general and realistic dependent setting, however, obtaining a tractable representation and estimating the decomposition from data remain challenging. In this work, we address this problem for continuous inputs. By combining Hilbert space methods with the generalized functional ANOVA, we build an explicit decomposition Riesz Basis allowing to easily compute the decomposition. Our formulation recovers the classical independent case and its associated orthogonal decomposition. Building on this representation, we propose a simple but mighty algorithm to estimate the decomposition from a data sample in a model-agnostic setting and we compare it empirically with several state-of-the-art explanation methods, demonstrating the power of the approach.

Directed Acyclic Graphs (DAGs) are central to uncovering causal structure in complex systems, yet learning a single DAG from data is often challenging: model uncertainty, finite samples, and a combinatorially large search space frequently yield unstable estimates. We propose DAGgr, a model averaging framework that aggregates multiple candidate DAGs into a single stable representation. Candidate graphs are weighted by their out-of-sample predictive likelihood across repeated data splits, and a thresholding rule on the resulting edge-importance scores guarantees that the aggregated graph is itself acyclic. We establish a finite-sample risk bound, prove that the procedure preserves acyclicity, and show that edge selection is consistent under mild conditions on the weights. Simulations across random, hub, and chain structures, together with an analysis of the Sachs et al. (2005) protein-signaling network, show that DAGgr matches or exceeds the best individual candidate while consistently outperforming bootstrap-aggregation baselines across structural recovery metrics.