arXiv subjects

Yongguo Yu

Publications and source records attributed to Yongguo Yu.

4 recordsLinked to original sources

arXiv2025

End-to-End Agentic RAG System Training for Traceable Diagnostic Reasoning

The integration of Large Language Models (LLMs) into healthcare is constrained by knowledge limitations, hallucinations, and a disconnect from Evidence-Based Medicine (EBM). While Retrieval-Augmented Generation (RAG) offers a solution, current systems often rely on static workflows that miss the iterative, hypothetico-deductive reasoning of clinicians. To address this, we introduce Deep-DxSearch, an agentic RAG system trained end-to-end via reinforcement learning (RL) for traceable diagnostic reasoning. Deep-DxSearch acts as an active investigator, treating the LLM as an agent within an environment of 16,000+ guideline-derived disease profiles, 150,000+ patient records for case-based reasoning, and over 27 million biomedical documents. Using soft verifiable rewards that co-optimize retrieval and reasoning, the model learns to formulate queries, evaluate evidence, and refine searches to close diagnostic gaps. Experiments show our end-to-end RL framework consistently outperforms prompt-engineering and training-free RAG methods. On in-distribution (ID) and out-of-distribution (OOD) benchmarks for common and rare diseases, Deep-DxSearch surpasses strong baselines-including GPT-4o, DeepSeek-R1, and medical-specific frameworks-achieving an average accuracy gain of 22.7% over the second-best model. In validation with 150 real-world cases, Deep-DxSearch boosts physicians' average diagnostic accuracy from 45.6% to 69.1%. These results indicate that evolving agentic systems to leverage statistical regularities in large-scale healthcare data is key for trustworthy diagnostic assistants. All data, code, and checkpoints are available at https://qiaoyu-zheng.github.io/Deep-DxSearch.

cs.CL↗

arXiv2025

An Agentic System for Rare Disease Diagnosis with Traceable Reasoning

Rare diseases affect over 300 million individuals worldwide, yet timely and accurate diagnosis remains an urgent challenge. Patients often endure a prolonged diagnostic odyssey exceeding five years, marked by repeated referrals, misdiagnoses, and unnecessary interventions, leading to delayed treatment and substantial emotional and economic burdens. Here we present DeepRare, a multi-agent system for rare disease differential diagnosis decision support powered by large language models, integrating over 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 testing results, to generate ranked diagnostic hypotheses with transparent reasoning linked to verifiable medical evidence. Evaluated across nine datasets from literature, case reports and clinical centres across Asia, North America and Europe spanning 14 medical specialties, DeepRare demonstrates exceptional performance on 3,134 diseases. In human-phenotype-ontology-based tasks, it achieves an average Recall@1 of 57.18%, outperforming the next-best method by 23.79%; in multi-modal tests, it reaches 69.1% compared with Exomiser's 55.9% on 168 cases. Expert review achieved 95.4% agreement on its reasoning chains, confirming their validity and traceability. Our work not only advances rare disease diagnosis but also demonstrates how the latest powerful large-language-model-driven agentic systems can reshape current clinical workflows.

cs.CL↗

arXiv2025

An Inclusive Foundation Model for Generalizable Cytogenetics in Precision Oncology

Chromosome analysis is vital for diagnosing genetic disorders and guiding cancer therapy decisions through the identification of somatic clonal aberrations. However, developing an AI model are hindered by the overwhelming complexity and diversity of chromosomal abnormalities, requiring extensive annotation efforts, while automated methods remain task-specific and lack generalizability due to the scarcity of comprehensive datasets spanning diverse resource conditions. Here, we introduce CHROMA, a foundation model for cytogenomics, designed to overcome these challenges by learning generalizable representations of chromosomal abnormalities. Pre-trained on over 84,000 specimens (~4 million chromosomal images) via self-supervised learning, CHROMA outperforms other methods across all types of abnormalities, even when trained on fewer labelled data and more imbalanced datasets. By facilitating comprehensive mapping of instability and clonal leisons across various aberration types, CHROMA offers a scalable and generalizable solution for reliable and automated clinical analysis, reducing the annotation workload for experts and advancing precision oncology through the early detection of rare genomic abnormalities, enabling broad clinical AI applications and making advanced genomic analysis more accessible.

q-bio.QM↗

arXiv2025

An LLM-Driven Multi-Agent Debate System for Mendelian Diseases

Accurate diagnosis of Mendelian diseases is crucial for precision therapy and assistance in preimplantation genetic diagnosis. However, existing methods often fall short of clinical standards or depend on extensive datasets to build pretrained machine learning models. To address this, we introduce an innovative LLM-Driven multi-agent debate system (MD2GPS) with natural language explanations of the diagnostic results. It utilizes a language model to transform results from data-driven and knowledge-driven agents into natural language, then fostering a debate between these two specialized agents. This system has been tested on 1,185 samples across four independent datasets, enhancing the TOP1 accuracy from 42.9% to 66% on average. Additionally, in a challenging cohort of 72 cases, MD2GPS identified potential pathogenic genes in 12 patients, reducing the diagnostic time by 90%. The methods within each module of this multi-agent debate system are also replaceable, facilitating its adaptation for diagnosing and researching other complex diseases.

q-bio.GN↗