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Updated: May 21, 2026

Evidence-based Knowledge Synthesis and Hypothesis Validation: Navigating Biomedical Knowledge Bases via Explainable AI and Agentic Systems
Published on: June 13, 2025
Automated biomedical hypothesis generation with time-aware hypergraph contrastive learning
Amir Hassan Shariatmadari1, Sikun Guo1, Nathan C Sheffield2
1Department of Computer Science, University of Virginia, 85 Engineer's Way, Charlottesville, Virginia 22903 USA.
Abstract:
Research in scientific domains now generates more than a million articles annually, overwhelming researchers and hindering discovery. This surge has sparked interest in biomedical hypothesis generation (HG), which aims to uncover implicit patterns among biomedical concepts. Most existing methods focus on pairwise link prediction, overlooking the complex, multi-concept relationships underlying many breakthroughs. We introduce HyHG, a temporal Hypergraph contrastive learning framework for biomedical Hypothesis Generation, which redefines hypotheses as hyperedges-sets of co-mentioned concepts in an article. By representing articles as hyperedges and organizing them into a temporal hypergraph, HyHG captures the evolution of scientific ideas over time. A transformer-based architecture learns from historical hyperedge sequences to predict future hyperedges-sets of concepts likely to co-occur in the future literature. To distinguish genuine hypotheses from misleading ones, HyHG employs a time-anchored contrastive loss and hard negative sampling based on minimal edits to real hyperedges. We demonstrate that HyHG achieves state-of-the-art performance on three biomedical datasets. Our code and data are available at: https://github.com/amir-hassan25/Temporal-Hypergraph-Contrastive-Learning.
