arXiv subjects

Robert Tibshirani

Publications and source records attributed to Robert Tibshirani.

At least 19 recordsLinked to original sources

arXiv2026

A Large-Scale Vision-Language Dataset Derived from Open Scientific Literature to Advance Biomedical Generalist AI

Despite the excitement behind biomedical artificial intelligence (AI), access to high-quality, diverse, and large-scale data - the foundation for modern AI systems - is still a bottleneck to unlocking its full potential. To address this gap, we introduce Biomedica, an open-source dataset derived from the PubMed Central Open Access subset, containing over 6 million scientific articles and 24 million image-text pairs, along with 27 metadata fields (including expert human annotations). To overcome the challenges of accessing our large-scale dataset, we provide scalable streaming and search APIs through a web server, facilitating seamless integration with AI systems. We demonstrate the utility of the Biomedica dataset by building embedding models, chat-style models, and retrieval-augmented chat agents. Notably, all our AI models surpass previous open systems in their respective categories, underscoring the critical role of diverse, high-quality, and large-scale biomedical data.

cs.CL↗

arXiv2026

Another look at predicting molecular breast cancer subtypes from the METABRIC data

Classifying patients into different clusters based on genomic data can offer valuable insights into their projected disease-specific survival trajectories over time. Here we apply two supervised learning methods---Nearest Shrunken Centroids and LASSO--- to the METABRIC Breast Cancer data {metabric} of 1980 patients and 754 genes to perform this task. The {pamr} R package implements the Nearest Shrunken Centroids classifier and the { glmnet} R package is used to fit an ungrouped multinomial model, a grouped multinomial model, and a One-Versus-Rest model. Splitting our data into discovery and validation sets, we evaluate all four models' classification performance and the survival implications of their class predictions using cross validation and Kaplan-Meier curves. We find that the One-Versus-Rest model produces the lowest misclassification error of 0.0572 and the lowest median log-rank test of 0.380 statistic measuring the similarity between its Kaplan-Meier curves and the discovery set's true Kaplan-Meier curves. We show that a multinomial classification task split into several LASSO binomial classifiers offers promising results for patient clustering.

stat.AP↗

arXiv2026

ERICA: Quantifying Replicability of Cluster Analysis

Despite being ubiquitous in science, clustering lacks a unified framework for quantitatively evaluating the replicability of its results. We present evaluating replicability via iterative clustering assignments (ERICA), a method for determining whether clusters can be identified reproducibly in a dataset. The pipeline computes a statistic that determines whether reproducible cluster structure is present in a dataset. Quantitative visualization methods are also introduced to characterize similarities between clusters and identify observations that may represent outliers or unstable assignments. Experiments on synthetic datasets demonstrate that ERICA successfully identifies reproducible cluster structure. In contrast, application of ERICA to three breast cancer gene-expression datasets reveals instances in which clustering solutions are not reproducible. The study underscores the importance of rigorously evaluating clustering solutions and provides a practical framework for doing so.

stat.ML↗

arXiv2026

MMBU: A Massive Multi-modal Biomedical Understanding Benchmark to Probe the Perception Capabilities of Vision-Language Models

Vision and language models (VLMs) hold immense promise to transform biomedical imaging workflows, from detecting lesions in chest X-rays to profiling cellular features in microscopy. Realizing this potential, however, requires robust and fine-grained visual perception. Models need to correctly interpret subtle features in images, and they must do so across diverse biomedical modalities, scales, and contexts. Nevertheless, current benchmarks remain limited. To address these gaps, we introduce the Massive Multimodal Biomedical Understanding (MMBU) benchmark. It is the largest biomedical vision and language benchmark to date, covering 35 submodalities with rich structured metadata. It includes both open and closed versions of ungrounded classification, grounded classification, and object detection, enabling systematic evaluation of model performance across biological scales, clinical settings, and imaging modalities. Evaluating 15 open-weight and 2 frontier VLMs, we find that while medical adaptation provides measurable gains for some models, the high accuracy often reported on established benchmarks can mask deficiencies in visual perception and domain generalization.

cs.CV↗

arXiv2026

Nonparametric Regression Discontinuity Designs with Survival Outcomes

Quasi-experimental evaluations are central for generating real-world causal evidence and complementing insights from randomized trials. The regression discontinuity design (RDD) is a quasi-experimental design that can be used to estimate the causal effect of treatments that are assigned based on a running variable crossing a threshold. Such threshold-based rules are ubiquitous in healthcare, where predictive and prognostic biomarkers frequently guide treatment decisions. However, standard RD estimators rely on complete outcome data, an assumption often violated in time-to-event analyses where censoring arises from loss to follow-up. To address this issue, we propose a nonparametric approach that leverages doubly robust censoring corrections and can be paired with existing RD estimators. Our approach can handle multiple survival endpoints, long follow-up times, and covariate-dependent variation in survival and censoring. We discuss the relevance of our approach across multiple areas of applications and demonstrate its usefulness through simulations and the prostate component of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial where our new approach offers several advantages, including higher efficiency and robustness to misspecification. We have also developed an open-source software package, $\texttt{rdsurvival}$, for the $\texttt{R}$ language.

stat.ML↗

arXiv2026

Univariate-Guided Sparse Regression for Biobank-Scale High-Dimensional Omics Data

We present a scalable framework for computing polygenic risk scores (PRS) in high-dimensional genomic settings using the recently introduced Univariate-Guided Sparse Regression (uniLasso). UniLasso is a two-stage penalized regression procedure that leverages univariate coefficients and magnitudes to stabilize feature selection and enhance interpretability. Building on its theoretical and empirical advantages, we adapt uniLasso for application to the UK Biobank, a population-based repository comprising over one million genetic variants measured on hundreds of thousands of individuals from the United Kingdom. We further extend the framework to incorporate external summary statistics to increase predictive accuracy. Our results demonstrate that uniLasso attains predictive performance comparable to standard Lasso while selecting substantially fewer variants, yielding sparser and more interpretable models. Moreover, it exhibits superior performance in estimating PRS relative to its competitors, such as PRS-CS. Integrating external scores further improves prediction while maintaining sparsity.

stat.ME↗

arXiv2026

Univariate-Guided Interaction Modeling

We propose a procedure for sparse regression with pairwise interactions, by generalizing the Univariate Guided Sparse Regression (UniLasso) methodology. A central contribution is our introduction of a concept of univariate (or marginal) interactions. Using this concept, we propose two algorithms -- uniPairs and uniPairs-2stage -- , and evaluate their performance against established methods, including Glinternet and Sprinter. We show that our framework yields sparser models with more interpretable interactions. We also prove support recovery results for our proposal under suitable conditions.

stat.ME↗

arXiv2025

Supervised learning pays attention

In-context learning with attention enables large neural networks to make context-specific predictions by selectively focusing on relevant examples. Here, we adapt this idea to supervised learning procedures such as lasso regression and gradient boosting, for tabular data. Our goals are to (1) flexibly fit personalized models for each prediction point and (2) retain model simplicity and interpretability. Our method fits a local model for each test observation by weighting the training data according to attention, a supervised similarity measure that emphasizes features and interactions that are predictive of the outcome. Attention weighting allows the method to adapt to heterogeneous data in a data-driven way, without requiring cluster or similarity pre-specification. Further, our approach is uniquely interpretable: for each test observation, we identify which features are most predictive and which training observations are most relevant. We then show how to use attention weighting for time series and spatial data, and we present a method for adapting pretrained tree-based models to distributional shift using attention-weighted residual corrections. Across real and simulated datasets, attention weighting improves predictive performance while preserving interpretability, and theory shows that attention-weighting linear models attain lower mean squared error than the standard linear model under mixture-of-models data-generating processes with known subgroup structure.

stat.ML↗

arXiv2025

Lassoed Forests: Random Forests with Adaptive Lasso Post-selection

Random forests are a statistical learning technique that use bootstrap aggregation to average high-variance and low-bias trees. Improvements to random forests, such as applying Lasso regression to the tree predictions, have been proposed in order to reduce model bias. However, these changes can sometimes degrade performance (e.g., an increase in mean squared error). In this paper, we show in theory that the relative performance of these two methods, standard and Lasso-weighted random forests, depends on the signal-to-noise ratio. We further propose a unified framework to combine random forests and Lasso selection by applying adaptive weighting and show mathematically that it can strictly outperform the other two methods. We compare the three methods through simulation, including bias-variance decomposition, error estimates evaluation, and variable importance analysis. We also show the versatility of our method by applications to a variety of real-world datasets.

stat.ML↗

arXiv2025

No Tokens Wasted: Leveraging Long Context in Biomedical Vision-Language Models

Embedding vision-language models (VLMs) are typically pretrained with short text windows (<77 tokens), which forces the truncation of long-format captions. Yet, the distribution of biomedical captions from large-scale open source literature reveals that a huge portion of captions far exceed 77 tokens. To this end, we investigate the impact of pretraining on long-format biomedical captions by extending the context length of text encoders in VLMs. We find that longer context (thus, enabling additional supervision provided in long-format captions) correlates with better retrieval and classification performance. Given this finding, we introduce BIOMEDICA-LongCAP, a dataset of 1M image-caption pairs enriched with context-aware descriptions from full-text articles, providing longer and additional textual supervision. Using BIOMEDICA-LongCAP, we train BMC-LongCLIP, a long-context biomedical VLM with a text encoder supporting windows of up to 512 tokens. Our model extends context capacity by 6.6x, reducing token waste from 55% to just 2.2%. On long-caption retrieval benchmarks, BMC-LongCLIP achieves up to +30% absolute gains in Recall@1 and +2% average improvements in classification, while also converging faster than short-context. Our results demonstrate that long-context modeling is a promising direction for advancing biomedical VLMs.

cs.CV↗

arXiv2025

LLM-Lasso: A Robust Framework for Domain-Informed Feature Selection and Regularization

We introduce LLM-Lasso, a novel framework that leverages large language models (LLMs) to guide feature selection in Lasso $\ell_1$ regression. Unlike traditional methods that rely solely on numerical data, LLM-Lasso incorporates domain-specific knowledge extracted from natural language, enhanced through a retrieval-augmented generation (RAG) pipeline, to seamlessly integrate data-driven modeling with contextual insights. Specifically, the LLM generates penalty factors for each feature, which are converted into weights for the Lasso penalty using a simple, tunable model. Features identified as more relevant by the LLM receive lower penalties, increasing their likelihood of being retained in the final model, while less relevant features are assigned higher penalties, reducing their influence. Importantly, LLM-Lasso has an internal validation step that determines how much to trust the contextual knowledge in our prediction pipeline. Hence it addresses key challenges in robustness, making it suitable for mitigating potential inaccuracies or hallucinations from the LLM. In various biomedical case studies, LLM-Lasso outperforms standard Lasso and existing feature selection baselines, all while ensuring the LLM operates without prior access to the datasets. To our knowledge, this is the first approach to effectively integrate conventional feature selection techniques directly with LLM-based domain-specific reasoning.

cs.LG↗

arXiv2025

Univariate-Guided Sparse Regression

In this paper, we introduce ``UniLasso'' -- a novel statistical method for sparse regression. This two-stage approach preserves the signs of the univariate coefficients and leverages their magnitude. Both of these properties are attractive for stability and interpretation of the model. Through comprehensive simulations and applications to real-world datasets, we demonstrate that UniLasso outperforms Lasso in various settings, particularly in terms of sparsity and model interpretability. We prove asymptotic support recovery and mean-squared error consistency under a set of conditions different from the well-known irrepresentability conditions for the Lasso. Extensions to generalized linear models (GLMs) and Cox regression are also discussed.

stat.ME↗

arXiv2025

Statistical Learning for Heterogeneous Treatment Effects: Pretraining, Prognosis, and Prediction

Robust estimation of heterogeneous treatment effects is a fundamental challenge for optimal decision-making in domains ranging from personalized medicine to educational policy. In recent years, predictive machine learning has emerged as a valuable toolbox for causal estimation, enabling more flexible effect estimation. However, accurately estimating conditional average treatment effects (CATE) remains a major challenge, particularly in the presence of many covariates. In this article, we propose pretraining strategies that leverage a phenomenon in real-world applications: factors that are prognostic of the outcome are frequently also predictive of treatment effect heterogeneity. In medicine, for example, components of the same biological signaling pathways frequently influence both baseline risk and treatment response. Specifically, we demonstrate our approach within the R-learner framework, which estimates the CATE by solving individual prediction problems based on a residualized loss. We use this structure to incorporate side information and develop models that can exploit synergies between risk prediction and causal effect estimation. In settings where these synergies are present, this cross-task learning enables more accurate signal detection, yields lower estimation error, reduced false discovery rates, and higher power for detecting heterogeneity.

stat.ML↗

arXiv2025

Pre-validation Revisited

Pre-validation is a way to build prediction model with two datasets of significantly different feature dimensions. Previous work showed that the asymptotic distribution of the resulting test statistic for the pre-validated predictor deviates from a standard Normal, hence leads to issues in hypothesis testing. In this paper, we revisit the pre-validation procedure and extend the problem formulation without any independence assumption on the two feature sets. We propose not only an analytical distribution of the test statistic for the pre-validated predictor under certain models, but also a generic bootstrap procedure to conduct inference. We show properties and benefits of pre-validation in prediction, inference and error estimation by simulations and applications, including analysis of a breast cancer study and a synthetic GWAS example.

stat.ME↗

arXiv2025

BIOMEDICA: An Open Biomedical Image-Caption Archive, Dataset, and Vision-Language Models Derived from Scientific Literature

The development of vision-language models (VLMs) is driven by large-scale and diverse multimodal datasets. However, progress toward generalist biomedical VLMs is limited by the lack of annotated, publicly accessible datasets across biology and medicine. Existing efforts are restricted to narrow domains, missing the full diversity of biomedical knowledge encoded in scientific literature. To address this gap, we introduce BIOMEDICA, a scalable, open-source framework to extract, annotate, and serialize the entirety of the PubMed Central Open Access subset into an easy-to-use, publicly accessible dataset. Our framework produces a comprehensive archive with over 24 million unique image-text pairs from over 6 million articles. Metadata and expert-guided annotations are also provided. We demonstrate the utility and accessibility of our resource by releasing BMCA-CLIP, a suite of CLIP-style models continuously pre-trained on the BIOMEDICA dataset via streaming, eliminating the need to download 27 TB of data locally. On average, our models achieve state-of-the-art performance across 40 tasks - spanning pathology, radiology, ophthalmology, dermatology, surgery, molecular biology, parasitology, and cell biology - excelling in zero-shot classification with a 6.56% average improvement (as high as 29.8% and 17.5% in dermatology and ophthalmology, respectively), and stronger image-text retrieval, all while using 10x less compute. To foster reproducibility and collaboration, we release our codebase and dataset for the broader research community.

cs.CV↗

arXiv2025

Semiparametric conformal prediction

Many risk-sensitive applications require well-calibrated prediction sets over multiple, potentially correlated target variables, for which the prediction algorithm may report correlated errors. In this work, we aim to construct the conformal prediction set accounting for the joint correlation structure of the vector-valued non-conformity scores. Drawing from the rich literature on multivariate quantiles and semiparametric statistics, we propose an algorithm to estimate the $1-α$ quantile of the scores, where $α$ is the user-specified miscoverage rate. In particular, we flexibly estimate the joint cumulative distribution function (CDF) of the scores using nonparametric vine copulas and improve the asymptotic efficiency of the quantile estimate using its influence function. The vine decomposition allows our method to scale well to a large number of targets. As well as guaranteeing asymptotically exact coverage, our method yields desired coverage and competitive efficiency on a range of real-world regression problems, including those with missing-at-random labels in the calibration set.

cs.LG↗

arXiv2025

powerROC: An Interactive Web Tool for Sample Size Calculation in Assessing Models' Discriminative Abilities

Rigorous external validation is crucial for assessing the generalizability of prediction models, particularly by evaluating their discrimination (AUROC) on new data. This often involves comparing a new model's AUROC to that of an established reference model. However, many studies rely on arbitrary rules of thumb for sample size calculations, often resulting in underpowered analyses and unreliable conclusions. This paper reviews crucial concepts for accurate sample size determination in AUROC-based external validation studies, making the theory and practice more accessible to researchers and clinicians. We introduce powerROC, an open-source web tool designed to simplify these calculations, enabling both the evaluation of a single model and the comparison of two models. The tool offers guidance on selecting target precision levels and employs flexible approaches, leveraging either pilot data or user-defined probability distributions. We illustrate powerROC's utility through a case study on hospital mortality prediction using the MIMIC database.

stat.ME↗

arXiv2024

Adaptive Forward Stepwise Regression

This paper proposes a sparse regression method that continuously interpolates between Forward Stepwise selection (FS) and the LASSO. When tuned appropriately, our solutions are much sparser than typical LASSO fits but, unlike FS fits, benefit from the stabilizing effect of shrinkage. Our method, Adaptive Forward Stepwise Regression (AFS) addresses this need for sparser models with shrinkage. We show its connection with boosting via a soft-thresholding viewpoint and demonstrate the ease of adapting the method to classification tasks. In both simulations and real data, our method has lower mean squared error and fewer selected features across multiple settings compared to popular sparse modeling procedures.

stat.ME↗