Abstract:Mechanistic modeling via ordinary differential equations (ODEs) provides interpretable descriptions of complex dynamics and enables inference of underlying mechanisms, which is particularly valuable in clinical settings. However, in rare diseases, both the structure and parameters of the model are typically unknown, while individual-level data is scarce, noisy, heterogeneous, and subject to privacy constraints. In such settings, population-level summary statistics provide a practical privacy-preserving data representation, while capturing heterogeneity further requires modeling parameters as distributions rather than fixed values. Yet no existing method jointly discovers ODE structure and refines parameter distributions solely from summary statistics. We present AgentODE, an end-to-end framework that addresses this gap. An LLM proposes candidate ODE structures, while a tool-augmented inference agent iteratively refines parameter distributions through a diagnosis--update loop, operating on population-level summary statistics alone. We evaluate AgentODE on three benchmark problems across different fields and two clinical datasets, including the rare disease recessive dystrophic epidermolysis bullosa (RDEB), with only 231 observations across 46 patients. AgentODE recovers functionally consistent ODE structures across all settings, and experiments on RDEB demonstrates that in sparse and noisy data settings reasoning from summary statistics promotes mechanistically principled structure discovery, whereas baselines with individual-level data access recover implausible structures despite better predictive performance. AgentODE opens new possibilities for mechanistic modeling of rare diseases directly from population-level summary statistics, where data scarcity and privacy constraints have traditionally limited such analyses.
Abstract:Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic skin disorder for which clinicians greatly benefit from finding similar cases using images and clinical text. However, off-the-shelf foundation models do not reliably capture clinically meaningful features for this heterogeneous, long-tail disease, and structured measurement of agreement with experts is challenging. To address these gaps, we propose evaluating embedding spaces with expert ordinal comparisons (triplet judgments), which are fast to collect and encode implicit clinical similarity knowledge. We further introduce TriDerm, a multimodal framework that learns interpretable wound representations from small cohorts by integrating wound imagery, boundary masks, and expert reports. On the vision side, TriDerm adapts visual foundation models to RDEB using wound-level attention pooling and non-contrastive representation learning. For text, we prompt large language models with comparison queries and recover medically meaningful representations via soft ordinal embeddings (SOE). We show that visual and textual modalities capture complementary aspects of wound phenotype, and that fusing both modalities yields 73.5% agreement with experts, outperforming the best off-the-shelf single-modality foundation model by over 5.6 percentage points. We make the expert annotation tool, model code and representative dataset samples publicly available.