KMM-CP: Practical Conformal Prediction under Covariate Shift via Selective Kernel Mean Matching

Uncertainty quantification is essential for deploying machine learning models in high-stakes domains such as scientific discovery and healthcare. Conformal Prediction (CP) provides finite-sample coverage guarantees under exchangeability, an assumption often violated in practice due to distribution shift. Under covariate shift, restoring validity requires importance weighting, yet accurate density-ratio estimation becomes unstable when training and test distributions exhibit limited support overlap. We propose KMM-CP, a conformal prediction framework based on Kernel Mean Matching (KMM) for covariate-shift correction. We show that KMM directly controls the bias-variance components governing conformal coverage error by minimizing RKHS moment discrepancy under explicit weight constraints, and establish asymptotic coverage guarantees under mild conditions. We then introduce a selective extension that identifies regions of reliable support overlap and restricts conformal correction to this subset, further improving stability in low-overlap regimes. Experiments on molecular property prediction benchmarks with realistic distribution shifts show that KMM-CP reduces coverage gap by over 50% compared to existing approaches. The code is available at https://github.com/siddharthal/KMM-CP.

Making Conformal Predictors Robust in Healthcare Settings: a Case Study on EEG Classification

Quantifying uncertainty in clinical predictions is critical for high-stakes diagnosis tasks. Conformal prediction offers a principled approach by providing prediction sets with theoretical coverage guarantees. However, in practice, patient distribution shifts violate the i.i.d. assumptions underlying standard conformal methods, leading to poor coverage in healthcare settings. In this work, we evaluate several conformal prediction approaches on EEG seizure classification, a task with known distribution shift challenges and label uncertainty. We demonstrate that personalized calibration strategies can improve coverage by over 20 percentage points while maintaining comparable prediction set sizes. Our implementation is available via PyHealth, an open-source healthcare AI framework: https://github.com/sunlabuiuc/PyHealth.

PyHealth 2.0: A Comprehensive Open-Source Toolkit for Accessible and Reproducible Clinical Deep Learning

Difficulty replicating baselines, high computational costs, and required domain expertise create persistent barriers to clinical AI research. To address these challenges, we introduce PyHealth 2.0, an enhanced clinical deep learning toolkit that enables predictive modeling in as few as 7 lines of code. PyHealth 2.0 offers three key contributions: (1) a comprehensive toolkit addressing reproducibility and compatibility challenges by unifying 15+ datasets, 20+ clinical tasks, 25+ models, 5+ interpretability methods, and uncertainty quantification including conformal prediction within a single framework that supports diverse clinical data modalities - signals, imaging, and electronic health records - with translation of 5+ medical coding standards; (2) accessibility-focused design accommodating multimodal data and diverse computational resources with up to 39x faster processing and 20x lower memory usage, enabling work from 16GB laptops to production systems; and (3) an active open-source community of 400+ members lowering domain expertise barriers through extensive documentation, reproducible research contributions, and collaborations with academic health systems and industry partners, including multi-language support via RHealth. PyHealth 2.0 establishes an open-source foundation and community advancing accessible, reproducible healthcare AI. Available at pip install pyhealth.

Molecule Language Model with Augmented Pairs and Expertise Transfer

Understanding the molecules and their textual descriptions via molecule language models (MoLM) recently got a surge of interest among researchers. However, unique challenges exist in the field of MoLM due to 1) a limited amount of molecule-text paired data and 2) missing expertise that occurred due to the specialized areas of focus among the experts. To this end, we propose AMOLE, which 1) augments molecule-text pairs with structural similarity preserving loss, and 2) transfers the expertise between the molecules. Extensive experiments on various downstream tasks demonstrate the superiority of AMOLE in comprehending molecules and their descriptions, highlighting its potential for application in real-world drug discovery.

Conformal Drug Property Prediction with Density Estimation under Covariate Shift

In drug discovery, it is vital to confirm the predictions of pharmaceutical properties from computational models using costly wet-lab experiments. Hence, obtaining reliable uncertainty estimates is crucial for prioritizing drug molecules for subsequent experimental validation. Conformal Prediction (CP) is a promising tool for creating such prediction sets for molecular properties with a coverage guarantee. However, the exchangeability assumption of CP is often challenged with covariate shift in drug discovery tasks: Most datasets contain limited labeled data, which may not be representative of the vast chemical space from which molecules are drawn. To address this limitation, we propose a method called CoDrug that employs an energy-based model leveraging both training data and unlabelled data, and Kernel Density Estimation (KDE) to assess the densities of a molecule set. The estimated densities are then used to weigh the molecule samples while building prediction sets and rectifying for distribution shift. In extensive experiments involving realistic distribution drifts in various small-molecule drug discovery tasks, we demonstrate the ability of CoDrug to provide valid prediction sets and its utility in addressing the distribution shift arising from de novo drug design models. On average, using CoDrug can reduce the coverage gap by over 35% when compared to conformal prediction sets not adjusted for covariate shift.

Molecular De Novo Design through Transformer-based Reinforcement Learning

In this work, we introduce a method to fine-tune a Transformer-based generative model for molecular de novo design. Leveraging the superior sequence learning capacity of Transformers over Recurrent Neural Networks (RNNs), our model can generate molecular structures with desired properties effectively. In contrast to the traditional RNN-based models, our proposed method exhibits superior performance in generating compounds predicted to be active against various biological targets, capturing long-term dependencies in the molecular structure sequence. The model's efficacy is demonstrated across numerous tasks, including generating analogues to a query structure and producing compounds with particular attributes, outperforming the baseline RNN-based methods. Our approach can be used for scaffold hopping, library expansion starting from a single molecule, and generating compounds with high predicted activity against biological targets.