articleNatureFeb 18, 2026HYBRID OA

An agentic system for rare disease diagnosis with traceable reasoning

Shanghai Jiao Tong University · Shandong Jiaotong University · +7 more institutions

PubMed
Indexed incrossrefpubmed

Abstract

Rare diseases affect more than 300 million people worldwide1–3, yet timely and accurate diagnosis remains an urgent challenge1,3–5. Patients often endure a prolonged ‘diagnostic odyssey’ exceeding 5 years, marked by repeated referrals, misdiagnoses and unnecessary interventions, leading to delayed treatment and substantial emotional and economic burden4,5. Here we present DeepRare—a multi-agent system for rare disease differential diagnosis decision support6–8 powered by large language models, integrating more than 40 specialized tools and up-to-date knowledge sources. DeepRare processes heterogeneous clinical inputs, including free-text descriptions, structured human phenotype ontology terms and genetic…

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