Lennon J. Shikhman, Ying Qian, He Lics.LG q-bio.QM q-bio.TO
Computational models of blood clotting improve understanding of thrombus formation, but their clinical application remains limited because many model inputs are difficult to measure and patient-specific data are often sparse. We present a computational framework based on latent neural differential equations that infers unknown model parameters from sparse measurements and forecasts thrombosis progression. We demonstrate the framework using data generated from a multiphysics blood-clotting model in which clot growth is governed by the coagulation cascade and diffusion. Four known biochemical inputs (fibrinogen and factors IX, VIII, and V), together with sparse early clot-size observations, are used to infer the tissue-factor parameter and predict subsequent clot growth. We compare seven probabilistic methods: stochastic neural ordinary differential equations (SNODE), stochastic neural functional differential equations (SNFDE), a latent neural-process baseline, a monotone probabilistic deep ensemble, empirical trajectory retrieval, PCA-ridge Gaussian posterior, and Gompertz-curve retrieval. SNODE achieved the best performance in inferring the unknown input and forecasting future clot-growth trajectories. SNFDE performed similarly and consistently outperformed the other non-differential models. Prediction accuracy improved as more observations became available, whereas longer forecasting horizons increased uncertainty and decreased accuracy. Latent neural differential equations thus effectively combine parameter inference and clot-growth forecasting from sparse measurements, providing a promising foundation for personalized thrombosis modeling.
Hanning Yang, Meropi Karakioulaki, Lennart Purucker +3cs.LG cs.AI
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.
T. Lucas Makinen, Deaglan J. Bartlett, Niall Jeffrey +1cs.LG astro-ph.IM physics.comp-ph physics.data-an stat.ML
When two or more parameters or labels produce similar data, they are degenerate, or hard to distinguish. Degeneracies render both label prediction and inverse problems difficult, since both machine learning algorithms and probabilistic samplers rely on the distinguishability of data and its gradients with respect to parameters. However, identifying degeneracies in physical models or real-world datasets can be elucidating about the choice of model or the underlying process that produces the data. We present the degeneracy distillery, a method that (1) detects and (2) resolves degenerate parameter combinations (a) automatically and (b) symbolically, from parameter-data (or parameter-simulation) pairs alone, through estimation and flattening of the Fisher information matrix. By exploring the information geometry of the likelihood, we characterize degeneracies as an intrinsic property of the physical model, requiring no realised data observation. We demonstrate our approach on a range of synthetic and real-world problems, discovering symbolic coordinate transformations that identify the combinations of parameters of a model which yield independent effects on the data. The resulting coordinates flatten the Fisher information in expectation globally, in contrast to posterior-based methods that flatten only at a single point, and substantially reduce the simulation budget required for downstream neural posterior estimation. In test cases we require up to $10\times$ fewer simulations for posterior estimation at matched validation calibration whilst simultaneously gaining physical insight on the system.
We propose a Koopman-enhanced physics-informed neural network (K--PINN) framework for parameter inference and forecasting in nonlinear epidemic models. This method combines Koopman operator theory and physics-informed learning. It maps epidemic states into a latent observable space where the dynamics evolve approximately linearly while satisfying the governing epidemic equations through automatic differentiation. This integration improves interpretability, parameter identifiability, and long-term predictive stability. We apply the proposed framework to a normalized SEIRSD epidemic model and evaluate it using synthetic monkeypox (Mpox) data and real-world datasets from Germany, Morocco, and Sweden for the SARS-CoV-2 virus. Synthetic trajectories are generated using a structure-preserving, nonstandard finite difference scheme to ensure reliable training data. Numerical results demonstrate that K--PINN achieves more accurate parameter estimation, trajectory reconstruction, and long-term forecasting than classical PINNs and Koopman-EDMD approaches. These results suggest that K--PINN is an effective machine learning framework for epidemic modeling that can be extended to more complex systems.
Federico Semenzato, Benjamin D. Wandelt, Michele Liguori +1astro-ph.CO cs.LG
Recovering cosmological information beyond the power spectrum is a central goal for upcoming cosmological surveys, since late-time non-Gaussian signal in the matter density cannot be accessed through two-point statistics alone. Marked statistics fold part of this information back into the two-point level by reweighting the field with non-linear functions. We propose a neural marking scheme to generalize this process through a set of interpretable, physically motivated transformations that directly allow to interpret the gain in cosmological information at the morphological level. We employ a contrastive learning objective to align learnable marked summaries with the underlying cosmological parameters. At $k_{\max}=0.2\,h\mathrm{Mpc}^{-1}$, our neural mark tightens the marginalized constraint on $σ_8$ by $2.9\times$ and on $Ω_m$ by $1.8\times$ compared to classical marks, breaking the $Ω_m-σ_8$ degeneracy at the Fisher information level. It further reduces the parameter MSE across our cosmological parameter prior by $1.45\times$ over the best classical mark. The learned latent geometry aligns with the $Ω_m$ and $σ_8$ directions in parameter space, indicating that the contrastive objective recovers the dominant axes of cosmological information. Our approach opens the door to more powerful, interpretable summary statistics for cosmological inference.
Hai-Ling Lu, Yu-Yang Li, Yin-Bi Li +4astro-ph.IM astro-ph.SR cs.LG
Stellar spectra encode key information on the physical properties and chemical compositions of stars. Accurate stellar parameter determination is essential for addressing major questions such as galaxy and stellar evolution. Large-scale spectroscopic surveys have accumulated unprecedented spectral data. Traditional feature extraction or model-fitting approaches struggle with high-dimensional, massive datasets, limited generalization, and computational inefficiency. Recent advances in large language models demonstrate strong generalization and feature-learning in tasks like natural language processing, DNA/RNA sequence analysis, and protein/chemical parsing. Stellar spectra are continuous sequential signals, enabling the transfer of language models to stellar spectroscopy. Here, we propose a two-stage large language model framework for stellar parameter inference, achieving accurate estimation of effective temperature, surface gravity, metallicity, and abundances of ~20 chemical elements. Scaling-law analyses show systematic performance improvements with increasing data, providing a scalable framework for forthcoming large-scale surveys.