James Zou
Publications
A Versatile AI Agent for Rare Disease Diagnosis and Risk Gene Prioritization
Accurate and timely diagnosis is essential for effective treatment, particularly in the context of rare diseases. However, current diagnostic workflows often lead to prolonged assessment times and low accuracy. To address these limitations, we introduce Hygieia, a multi-modal AI agent system designed to support precision disease diagnosis by integrating diverse data sources, including phenotypic features, genetic profiles, and clinical records. Hygieia features a router-based and knowledge-enhanced framework that mitigates hallucination and tailors diagnostic strategies to different disease categories. Notably, it prioritizes risk-related genomic factors for rare diseases and provides confidence scores to assist clinical decision-making. We conducted a comprehensive evaluation demonstrating that Hygieia achieves state-of-the-art performance across multiple diagnostic benchmarks. In collaboration with clinical experts from Yale School of Medicine and Duke-NUS Medical School, we further validated its practical utility by showing (1) Hygieia's superior diagnostic performance compared to physicians with an improvement from 12%-60% and (2) its effectiveness in assisting clinicians with medical records for handling real-world cases. Our findings indicate that Hygieia not only enhances diagnostic accuracy and interpretability but also significantly reduces clinician workload, highlighting its potential as a valuable tool in clinical decision support systems.
Beyond Semantic Similarity: Rethinking Retrieval for Agentic Search via Direct Corpus Interaction
Modern retrieval systems, whether lexical or semantic, expose a corpus through a fixed similarity interface that compresses access into a single top-k retrieval step before reasoning. This abstraction is efficient, but for agentic search, it becomes a bottleneck: exact lexical constraints, sparse clue conjunctions, local context checks, and multi-step hypothesis refinement are difficult to implement by calling a conventional off-the-shelf retriever, and evidence filtered out early cannot be recovered by stronger downstream reasoning. Agentic tasks further exacerbate this limitation because they require agents to orchestrate multiple steps, including discovering intermediate entities, combining weak clues, and revising the plan after observing partial evidence. To tackle the limitation, we study direct corpus interaction (DCI), where an agent searches the raw corpus directly with general-purpose terminal tools (e.g., grep, file reads, shell commands, lightweight scripts), without any embedding model, vector index, or retrieval API. This approach requires no offline indexing and adapts naturally to evolving local corpora. Across IR benchmarks and end-to-end agentic search tasks, this simple setup substantially outperforms strong sparse, dense, and reranking baselines on several BRIGHT and BEIR datasets, and attains strong accuracy on BrowseComp-Plus and multi-hop QA without relying on any conventional semantic retriever. Our results indicate that as language agents become stronger, retrieval quality depends not only on reasoning ability but also on the resolution of the interface through which the model interacts with the corpus, with which DCI opens a broader interface-design space for agentic search.