BioTrace: A Verifiable Pathology Agent for Tracing Molecular-to-Phenotype Evidence in Whole-Slide VQA

Whole-slide pathology visual question answering (VQA) often requires inferring clinically relevant phenotypes from evidence distributed across tissue regions and scales. Existing methods, including recent pathology agents, mainly acquire and reason over morphological evidence, leaving gene- and pathway-level biological support largely unexposed. Moreover, agent-based methods typically treat retrieved observations as additional context, without explicitly determining whether the evidence required by the question has been sufficiently resolved. To address these limitations, we introduce BioTrace, an agent system that traces question-specific evidence along a biological hierarchy with iterative evidence acquisition and verification. BioTrace organizes multiscale H&E representations into a Gene–Pathway–Phenotype evidence space, exposing concept-level predictions, concept-specific spatial responses, and supporting biological associations as queryable evidence alongside morphological observations. During inference, a pathology knowledge-guided verifier assesses evidence sufficiency, while unresolved evidence requirements guide subsequent acquisition. Experiments show that the learned evidence space performs strongly across phenotype-, pathway-, and gene-level prediction tasks. Building on this evidence space, the full BioTrace system consistently outperforms the compared pathology VQA and agent baselines on WSI-VQA and SlideBench-BCNB.