Dose-Response Estimation

Learning a response law for continuous decisions from observational time series is central to many real-world decision systems, yet temporal non-stationarity poses a fundamental challenge: as outcomes drift over time, naively pooled models can conflate action effects with shifting baselines and even reverse action rankings. Even when the one-step response is identifiable, unrestricted cross-time generalization remains fundamentally ill-posed. We therefore seek the part of the response that remains stable for decisions even when outcome levels do not. We propose deployable causal action geometry: the action-response shape that remains after anchoring away action-independent level shifts on a selected link scale and profiling out positive amplitude variation. Building on this target, we develop a two-stage orthogonal estimator that first obtains cross-fitted pilot estimates of anchored responses and then performs honest profiled selection over link, representation, and shape classes. The resulting estimator admits oracle guarantees for the restricted target and, under approximate persistence, produces decision rules that remain near optimal in future periods. Experiments on synthetic data and Dominick's support the proposed target and its transfer behavior. In a randomized Taobao A/B test, the deployed system improves GMV and purchase counts by $1.16\%$ and $1.70\%$.

Estimating causal effects with continuous treatments in observational studies is challenging due to confounding, model misspecification, and high-dimensional covariates. We propose the Weighted Spline-Expanded Network (WSENet), an end-to-end neural framework that addresses these challenges by combining covariate balancing, structured treatment embedding, and bias-corrected outcome estimation. WSENet first applies Distance Covariate Optimal Weights to induce distributional independence between covariates and treatment without relying on parametric models. It then learns the conditional outcome via a structured network that fuses outcome-relevant representations of covariates with a spline-expanded treatment input, enabling smooth and flexible modeling of the dose-response relationship. To mitigate residual bias, we introduce Weighted Targeted Regularization, a correction technique based on efficient influence functions that yields a doubly robust estimator. Extensive evaluations on semi-synthetic and real-world datasets, including high-dimensional genomic and environmental health data, demonstrate that WSENet consistently outperforms existing baselines in both accuracy and stability.

High-throughput drug screening relies on low-cost primary assays to prioritize compounds for more expensive dose-response profiling, where potency is ultimately quantified. Current screening strategies largely focus on identifying compounds that will confirm biological activity on follow-up, implicitly assuming that confirmed activity will also yield a usable potency estimate. However, confirmed biological activity in screening does not necessarily translate into a quantifiable potency, because active compounds can still fail to produce a reportable dose-response estimate. We therefore present a framework for modeling quantifiability, whether follow-up testing will yield a usable potency estimate, as a distinct triage objective from biological activity. Quantifiability was strongly predictable from the preceding low-cost screen, with most predictive information arising from the observed screening features rather than molecular structure. Response-based predictors remained robust on previously unseen chemical scaffolds and generalized across held-out assay-mechanism families, while the probability of successful quantification varied strongly with response amplitude and assay context. These findings establish experimental measurability, distinct from biological activity, as a predictable property of screening outcomes and show that quantifiability-aware triage can improve the allocation of costly dose-response profiling capacity.

Generative modeling has shown increasing promise for predicting cellular perturbation effects under chemical compound treatments. Existing approaches either model perturbation as a distribution-to-distribution mapping without explicit concentration handling, or treat concentration as a discrete class label, precluding continuous dose control. We introduce a joint flow matching approach that simultaneously models cell latents and drug concentration via a dual-timestep formulation, enabling dose-conditioned single-cell morphing through the invertibility of flow matching. The joint formulation induces a monotonic dose-response geometry in latent space and additionally supports concentration estimation from cell morphology. As proof of concept, we further demonstrate generalization to an unseen dose held out during training. Empirically, our method achieves competitive or improved per-concentration metrics on two compounds compared with representative baselines, while enabling capabilities structurally unavailable to discrete-class methods.

Predicting a patient's physiological trajectory under a planned treatment sequence is a prospective interventional problem, not standard time-series extrapolation. We study this problem in glucose management, where insulin and carbohydrate records are policy-dependent: future drivers are coupled to patient state, behavior, and clinical decision rules, so observational forecasting accuracy alone does not guarantee correct responses to planned interventions. We introduce Interventional Flow Matching (IFM), a continuous-time generative framework for physiologically constrained prospective forecasting. IFM conditions a flow-matching velocity field on patient history and planned future drivers in a bounded latent glucose space. Rather than embedding strict mechanistic glucose--insulin ODE equations or enforcing causality through rollout-based simulations, IFM uses a solver-free regularization: it penalizes the Jacobian of the instantaneous velocity field with respect to smoothed treatment drivers. This imposes signed, dose-bounded local sensitivities directly on the learned dynamics: insulin lowers glucose, carbohydrates raise it, and both responses remain within plausible ranges. On a simulated UVA/Padova type 1 diabetes cohort, IFM achieves the strongest balance between observed-driver RMSE and interventional response metrics. Across experiments, it consistently produces physiologically correct responses to both insulin and carbohydrate drivers while maintaining high directional, and ranking consistency.

Estimating the probability that a treatment outperforms a control for an individual patient, called the Individual Probability of Treatment Benefit (IPTB), offers a clinically intuitive alternative to population-average metrics. However, existing methods for IPTB estimation are largely confined to binary treatment settings, despite the prevalence of dose-varying interventions in clinical practice. We propose a general framework for IPTB estimation with ordinal outcomes under discrete dose assignments, called Dose-AIPTB (Dose Attention-based IPTB). Our approach recasts the problem as binary classification over the unobserved sign of the individual treatment effect, constructing pseudo-labels from covariate-similar pairwise comparisons and aggregating them via attention mechanisms or Nadaraya-Watson kernel regression. This formulation naturally accommodates multiple discrete dose levels, extending beyond the binary treatment paradigm. Through numerical experiments on real-world and synthetic data under covariate shift, varying sample sizes, and heterogeneous outcomes, we demonstrate that attention-based aggregation consistently outperforms kernel alternatives. The framework provides a foundation for personalized dose selection grounded in individual-level benefit probabilities. Codes implementing the model are publicly available at https://github.com/NTAILab/AIPTBDose.

We propose a novel doubly robust neural mean-embedding framework for proxy causal learning (PCL) for continuous and structured treatments. PCL uses proxy variables and bridge functions to identify causal effects under unobserved confounding: either an outcome bridge or a treatment bridge can identify the target, while doubly robust methods combine both. Our framework learns both bridges with data-adaptive neural features and combines them into doubly robust estimators of population, treatment-conditional, and heterogeneous dose-response functions. Two features of our result are particularly notable: the treatment bridge can be learned without density ratios, and the same treatment bridge yields both population and heterogeneous responses, eliminating the need for a separate bridge fit. Our analysis shows that the doubly robust error is controlled by final-stage error and the smaller of the two projected bridge errors, with no separate density-ratio estimation error. Across challenging continuous- and structured-treatment benchmarks, our method outperforms neural single-bridge estimators and fixed-feature doubly robust estimators. Our implementation is available at https://github.com/BariscanBozkurt/DoublyRobust-PCL-Network.

Predicting the perceived intensity of odorants remains a fundamental challenge in sensory science due to the complex, non-linear behavior of their response, as well as the difficulty in correlating molecular structure with human perception. While traditional deep learning models, such as Graph Convolutional Networks (GCNs), excel at capturing molecular topology, they often fail to account for the biological and perceptual context of olfaction. This study introduces VIANA, a novel "tri-pillar" framework that integrates structural graph theory, character value embeddings, and phenomenological behavior. This methodology systematically evaluates knowledge transfer across three distinct domains: molecular structure via GCNs, semantic odor character values via Principal Odor Map (POM) embeddings, and biological dose-response logic via Hill's law. We demonstrate that knowledge transfer is not inherently positive; rather, a balance must be maintained in the volume of information provided to the model. While raw semantic data led to "information overload" in domain-informed models, applying Principal Component Analysis (PCA) to distill the 95% most impactful semantic variance yielded a superior "signal distillation" effect. Results indicate that the synthesis of these three knowledge transfer pillars significantly outperforms baseline structural models, with VIANA achieving a peak R^2 of 0.996 and a test Mean Squared Error (MSE) of 0.19. In this context, VIANA successfully captures the physical ceiling of saturation, the sensitivity of detection thresholds, and the nuance of odor character value expression, providing a domain grounded simulation of the human olfactory experience. This research provides a robust framework for digital olfaction, effectively bridging the gap between molecular informatics and sensory perception.