DeepRare
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Introduces DeepRare, a modular agentic system powered by LLMs to aid rare disease diagnosis from multimodal clinical inputs (text, HPO terms, VCFs). It generates ranked diagnostic hypotheses with fully traceable reasoning chains linked to verifiable medical sources, addressing a long-standing need for interpretability in clinical AI.
DeepRare is built on a 3-tier MCP-inspired architecture: a central LLM-powered host with memory, multiple specialized agent servers for tasks like phenotype extraction and variant prioritization, and access to over 40 tools and web-scale medical sources.
It demonstrates strong performance on 6,401 cases across 8 diverse datasets spanning 2,919 rare diseases, achieving 100% accuracy on 1,013 diseases and Recall@1 of 57.18%, outperforming the next best method (Claude-3.7-Sonnet-thinking) by +23.79% on HPO-only evaluations.
For multimodal inputs (HPO + gene), it achieves 70.60% Recall@1 on 109 whole-exome sequencing cases, outperforming Exomiser (53.20%). Expert review of 180 diagnostic reasoning chains showed 95.4% agreement, validating its medical soundness.
Ablation studies show that DeepRare’s agentic modules, especially self-reflection, similar case retrieval, and web knowledge, substantially improve LLM-only baselines by 28–70% across datasets, independent of which central LLM is used.
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