OPBench: A Graph Benchmark to Combat the Opioid Crisis

Graph Neural Networks (GNNs) have become the dominant framework for inductive graph-level learning. Yet most benchmarks focus on the regime $n \gg p$, where the number of graphs $n$ greatly exceeds the number of nodes per graph $p$. This overlooks biological domains such as omics, which operate in the opposite $n \ll p$ regime, characterized by large graphs of genes, transcripts, or proteins across few patient samples. This raises the question: how do GNNs perform in this low-sample, high-node omics setting? We introduce OgBench (Omics-Graph Bench), the first benchmarking platform for graph-level prediction in the $n \ll p$ regime characteristic of omics data. We provide a standardized, end-to-end modular infrastructure from raw omics data to families of featured graphs with varied structural properties. We benchmark classical GNNs, as well as GNNs designed for large graphs and omics applications, alongside MLPs and machine learning baselines to establish reference performances. Our results show that widely used GNNs often do not outperform simple MLPs and classical baselines. These findings challenge the prevailing assumption that graph structure inherently adds value in this domain, fostering a critical reassessment of current learning paradigms. Ultimately, by exposing these limitations, OgBench provides the open-source ecosystem necessary for the community to develop and validate novel architectures explicitly tailored for biological graphs. The code is available at https://github.com/geometric-intelligence/ogbench.

Opioid use disorder (OUD) remains a public health crisis in the United States, yet it is difficult to identify from electronic health records (EHRs) because missing diagnosis codes and supporting evidence are buried in clinical narratives. Accurate OUD identification is critical to support interventions and improve health outcomes. This study developed a rubric-guided large language model (LLM) that incorporated Optimization by PROmpting (OPRO) for OUD computable phenotyping (CP). The framework used an 18-item, expert-identified rubric to instruct LLMs to automatically extract critical text with supporting evidence to determine OUD flags. Two UF Health physicians (GMR and WMG) chart-reviewed 253 patients, including 68 OUD-positive cases. Our LLM-based computable phenotype (CP) achieved the best F1 score of 0.774 and an AUROC of 0.934, outperforming the machine learning-based CP using EHR and natural language processing-extracted variables, and zero-shot LLMs by relative F1 improvements of 12.8% and 44.4%, respectively. The proposed LLM-based CP could link LLM-extracted evidence to OUD phenotyping for better explainability.

Drug discovery is a costly and high-risk process, where toxicity-related failures remain a major cause of attrition in both preclinical and clinical stages. As a result, accurate early prediction of chemical toxicity is essential to reduce downstream costs and improve compound prioritization. In this context, graph deep learning (GDL) has emerged as a powerful paradigm for toxicity prediction, leveraging molecular graph representations to learn directly from chemical structure with improved expressivity over traditional approaches. Despite the growing number of proposed models, current literature-based comparisons are often difficult to interpret due to inconsistencies in datasets, preprocessing pipelines, and evaluation protocols. To address this limitation, we introduce a unified and standardized benchmarking framework for GDL-based toxicity prediction. We systematically evaluate more than 20 representative approaches under consistent experimental conditions and across multiple datasets and partitioning strategies, enabling a fair and reproducible comparison of model performance. In addition, we complement this empirical study with a structured literature analysis to contextualize existing methodological trends and performance claims. Our results provide a clearer and more reliable assessment of the current state of the field, highlighting both the strengths and limitations of existing graph-based approaches. To support transparency and reproducibility, we release our benchmarking framework as open-source software https://gitlab.citius.gal/noel.suarez/benchtox, allowing the community to evaluate and compare models under consistent conditions.