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React-to-Me: A Conversational Interface for Interactive Exploration of the Reactome Pathway Knowledgebase

Mohammadi H, Almodaresi F, Hogue GFJ, Wright A, Orlic-Milacic M, Li NT, Mawani A, Stein L

Research square, 2026

Abstract

The Reactome Pathway Knowledgebase (www.reactome.org) provides expert-curated information on human biological pathways, molecular interactions, and disease mechanisms. However, its complex data model and keyword-based search interface present accessibility barriers for non-expert users. In contrast, general-purpose conversational AI systems offer intuitive natural language interfaces but lack the domain-specificity, transparent sourcing, and factual reliability required for scientific applications. To address this gap, we developed React-to-Me (https://reactome.org/chat), a domain-specific conversational assistant that enables users to query Reactome using natural language while maintaining scientific rigor and source traceability. React-to-Me integrates hybrid retrieval-augmented generation (RAG) with constrained language model generation to ensure that all responses are grounded in curated Reactome content and directly linked to corresponding knowledgebase entries. When internal coverage is insufficient, the system defers to trusted external biomedical sources rather than generating speculative or unverified content. Computational benchmarking confirmed that combining semantic vector search with lexical keyword-based matching substantially improved contextual grounding and factual precision relative to dense-only retrieval baselines. In blinded expert evaluations, grounded responses were more likely to receive higher quality ratings than ungrounded counterparts (OR = 2.01,…

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