Ya Zhang

Weike Zhao, Chaoyi Wu, Yanjie Fan et al. · harvard

Rare diseases collectively affect over 300 million individuals worldwide, yet timely and accurate diagnosis remains a pervasive challenge. This is largely due to their clinical heterogeneity, low individual prevalence, and the limited familiarity most clinicians have with rare conditions. Here, we introduce DeepRare, the first rare disease diagnosis agentic system powered by a large language model (LLM), capable of processing heterogeneous clinical inputs. The system generates ranked diagnostic hypotheses for rare diseases, each accompanied by a transparent chain of reasoning that links intermediate analytic steps to verifiable medical evidence. DeepRare comprises three key components: a central host with a long-term memory module; specialized agent servers responsible for domain-specific analytical tasks integrating over 40 specialized tools and web-scale, up-to-date medical knowledge sources, ensuring access to the most current clinical information. This modular and scalable design enables complex diagnostic reasoning while maintaining traceability and adaptability. We evaluate DeepRare on eight datasets. The system demonstrates exceptional diagnostic performance among 2,919 diseases, achieving 100% accuracy for 1013 diseases. In HPO-based evaluations, DeepRare significantly outperforms other 15 methods, like traditional bioinformatics diagnostic tools, LLMs, and other agentic systems, achieving an average Recall@1 score of 57.18% and surpassing the second-best method (Reasoning LLM) by a substantial margin of 23.79 percentage points. For multi-modal input scenarios, DeepRare achieves 70.60% at Recall@1 compared to Exomiser's 53.20% in 109 cases. Manual verification of reasoning chains by clinical experts achieves 95.40% agreements. Furthermore, the DeepRare system has been implemented as a user-friendly web application http://raredx.cn/doctor.

Haofan Wu, Yin Huang, Yuqing Wu et al.

High-quality fundus images provide essential anatomical information for clinical screening and ophthalmic disease diagnosis. Yet, due to hardware limitations, operational variability, and patient compliance, fundus images often suffer from low resolution and signal-to-noise ratio. Recent years have witnessed promising progress in fundus image enhancement. However, existing works usually focus on restoring structural details or global characteristics of fundus images, lacking a unified image enhancement framework to recover comprehensive multi-scale information. Moreover, few methods pinpoint the target of image enhancement, e.g., lesions, which is crucial for medical image-based diagnosis. To address these challenges, we propose a multi-scale target-aware representation learning framework (MTRL-FIE) for efficient fundus image enhancement. Specifically, we propose a multi-scale feature encoder (MFE) that employs wavelet decomposition to embed both low-frequency structural information and high-frequency details. Next, we design a structure-preserving hierarchical decoder (SHD) to fuse multi-scale feature embeddings for real fundus image restoration. SHD integrates hierarchical fusion and group attention mechanisms to achieve adaptive feature fusion while retaining local structural smoothness. Meanwhile, a target-aware feature aggregation (TFA) module is used to enhance pathological regions and reduce artifacts. Experimental results on multiple fundus image datasets demonstrate the effectiveness and generalizability of MTRL-FIE for fundus image enhancement. Compared to state-of-the-art methods, MTRL-FIE achieves superior enhancement performance with a more lightweight architecture. Furthermore, our approach generalizes to other ophthalmic image processing tasks without supervised fine-tuning, highlighting its potential for clinical applications.