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Explainable differential diagnosis with dual-inference large language models

Shuang Zhou, Mingquan Lin, Sirui Ding, Jiashuo Wang, Canyu Chen, Genevieve B. Melton, James Zou, Rui Zhang

2025npj Health Systems16 citationsDOIOpen Access PDF

Abstract

Automatic differential diagnosis (DDx) involves identifying potential conditions that could explain a patient's symptoms and its accurate interpretation is of substantial significance. While large language models (LLMs) have demonstrated remarkable diagnostic accuracy, their capability to generate high-quality DDx explanations remains underexplored, largely due to the absence of specialized evaluation datasets and the inherent challenges of complex reasoning in LLMs. Therefore, building a tailored dataset and developing novel methods to elicit LLMs for generating precise DDx explanations are worth exploring. We developed the first publicly available DDx dataset, comprising expert-derived explanations for 570 clinical notes, to evaluate DDx explanations. Meanwhile, we proposed a novel framework, Dual-Inf, that could effectively harness LLMs to generate high-quality DDx explanations. To the best of our knowledge, it is the first study to tailor LLMs for DDx explanation and comprehensively evaluate their explainability. Overall, our study bridges a critical gap in DDx explanation, enhancing clinical decision-making.

Topics & Concepts

InferenceDual (grammatical number)Quality (philosophy)Interpretation (philosophy)Differential (mechanical device)Computer scienceMedicineArtificial intelligenceEngineeringLinguisticsEpistemologyProgramming languagePhilosophyAerospace engineeringTopic ModelingMachine Learning in HealthcareNatural Language Processing Techniques
Explainable differential diagnosis with dual-inference large language models | Litcius