arXiv subjects

Caleb N. Ellington

Publications and source records attributed to Caleb N. Ellington.

4 recordsLinked to original sources

arXiv2026

Context-Adaptive Inference: A Unified Statistical and Foundation-Model View

Modern predictive systems are expected to adapt their behavior to the specific situation they are facing. A clinical model should not treat every patient the same; a retrieval-augmented model should change its answer when given different evidence; a mixture-of-experts model should route different inputs to different experts. We call this capability context-adaptive inference: before predicting, the system uses information about the current context to specialize its parameters or computation for that instance. This article provides a unified view of context-adaptive inference across three traditions that are usually treated separately: (i) explicit adaptation in statistics (e.g. varying-coefficient models, local regression, hierarchical sharing), (ii) rapid task-specific adaptation in meta-learning and transfer, and (iii) implicit adaptation in large foundation models via prompting, retrieval, and expert routing. We formalize these approaches under a common objective: to map context $c$ to adapted parameters $θ(c)$, then to predict via $f(x; θ(c))$. Under squared loss, linear prediction heads, and fixed features, we prove that explicit parameter adaptation and implicit routing are mathematically equivalent to kernel ridge regression on joint features of inputs and context. Building on this bridge, we propose practical design principles and evaluation metrics including adaptation-efficiency, routing stability, and context-specific robustness to guide when to specialize, how to constrain that specialization, and how to audit context-adaptive models in deployment. Finally, we identify open problems in identifiability, robustness under distribution shift, and efficient large-scale adaptation, outlining design principles for methods that are scalable, reliable, and transparent in real-world settings.

stat.ML↗

arXiv2025

Scaling Structure Aware Virtual Screening to Billions of Molecules with SPRINT

Virtual screening of small molecules against protein targets can accelerate drug discovery and development by predicting drug-target interactions (DTIs). However, structure-based methods like molecular docking are too slow to allow for broad proteome-scale screens, limiting their application in screening for off-target effects or new molecular mechanisms. Recently, vector-based methods using protein language models (PLMs) have emerged as a complementary approach that bypasses explicit 3D structure modeling. Here, we develop SPRINT, a vector-based approach for screening entire chemical libraries against whole proteomes for DTIs and novel mechanisms of action. SPRINT improves on prior work by using a self-attention based architecture and structure-aware PLMs to learn drug-target co-embeddings for binder prediction, search, and retrieval. SPRINT achieves SOTA enrichment factors in virtual screening on LIT-PCBA, DTI classification benchmarks, and binding affinity prediction benchmarks, while providing interpretability in the form of residue-level attention maps. In addition to being both accurate and interpretable, SPRINT is ultra-fast: querying the whole human proteome against the ENAMINE Real Database (6.7B drugs) for the 100 most likely binders per protein takes 16 minutes. SPRINT promises to enable virtual screening at an unprecedented scale, opening up new opportunities for in silico drug repurposing and development. SPRINT is available on the web as ColabScreen: https://bit.ly/colab-screen

q-bio.BM↗

arXiv2024

Contextualized Policy Recovery: Modeling and Interpreting Medical Decisions with Adaptive Imitation Learning

Interpretable policy learning seeks to estimate intelligible decision policies from observed actions; however, existing models force a tradeoff between accuracy and interpretability, limiting data-driven interpretations of human decision-making processes. Fundamentally, existing approaches are burdened by this tradeoff because they represent the underlying decision process as a universal policy, when in fact human decisions are dynamic and can change drastically under different contexts. Thus, we develop Contextualized Policy Recovery (CPR), which re-frames the problem of modeling complex decision processes as a multi-task learning problem, where each context poses a unique task and complex decision policies can be constructed piece-wise from many simple context-specific policies. CPR models each context-specific policy as a linear map, and generates new policy models $\textit{on-demand}$ as contexts are updated with new observations. We provide two flavors of the CPR framework: one focusing on exact local interpretability, and one retaining full global interpretability. We assess CPR through studies on simulated and real data, achieving state-of-the-art performance on predicting antibiotic prescription in intensive care units ($+22\%$ AUROC vs. previous SOTA) and predicting MRI prescription for Alzheimer's patients ($+7.7\%$ AUROC vs. previous SOTA). With this improvement, CPR closes the accuracy gap between interpretable and black-box methods, allowing high-resolution exploration and analysis of context-specific decision models.

cs.LG↗

arXiv2023

Contextualized Machine Learning

We examine Contextualized Machine Learning (ML), a paradigm for learning heterogeneous and context-dependent effects. Contextualized ML estimates heterogeneous functions by applying deep learning to the meta-relationship between contextual information and context-specific parametric models. This is a form of varying-coefficient modeling that unifies existing frameworks including cluster analysis and cohort modeling by introducing two reusable concepts: a context encoder which translates sample context into model parameters, and sample-specific model which operates on sample predictors. We review the process of developing contextualized models, nonparametric inference from contextualized models, and identifiability conditions of contextualized models. Finally, we present the open-source PyTorch package ContextualizedML.

stat.ML↗