# Quantification of total uncertainty in the physics-informed reconstruction of CVSim-6 physiology

arXiv: https://arxiv.org/abs/2408.07201 · HTML: https://mlsanity.com/paper/2408.07201/

## Key facts

- Cited by 3 papers in the map (data through 14 Oct 2026).
- Builds on 43 of its 100 references that are in the map.
- First posted on arXiv 13 Aug 2024.

## Builds on (most cited first, 30 of 43)

- [Dropout as a Bayesian Approximation: Representing Model Uncertainty in Deep Learning](https://mlsanity.com/paper/1506.02142/) (2015)
- [Simple and Scalable Predictive Uncertainty Estimation using Deep Ensembles](https://mlsanity.com/paper/1612.01474/) (2016)
- [Variational Inference: A Review for Statisticians](https://mlsanity.com/paper/1601.00670/) (2016)
- [A Survey of Uncertainty in Deep Neural Networks](https://mlsanity.com/paper/2107.03342/) (2021)
- [Scientific Machine Learning through Physics-Informed Neural Networks: Where we are and What's next](https://mlsanity.com/paper/2201.05624/) (2022)
- [B-PINNs: Bayesian Physics-Informed Neural Networks for Forward and Inverse PDE Problems with Noisy Data](https://mlsanity.com/paper/2003.06097/) (2020)
- [Black Box Variational Inference](https://mlsanity.com/paper/1401.0118/) (2013)
- [Ensemble deep learning: A review](https://mlsanity.com/paper/2104.02395/) (2021)
- [Physics-informed neural networks with hard constraints for inverse design](https://mlsanity.com/paper/2102.04626/) (2021)
- [Uncertainty Quantification in Scientific Machine Learning: Methods, Metrics, and Comparisons](https://mlsanity.com/paper/2201.07766/) (2022)
- [Hyperparameter Ensembles for Robustness and Uncertainty Quantification](https://mlsanity.com/paper/2006.13570/) (2020)
- [Uncertainty Quantification and Deep Ensembles](https://mlsanity.com/paper/2007.08792/) (2020)
- [Physics-informed graph neural Galerkin networks: A unified framework for solving PDE-governed forward and inverse problems](https://mlsanity.com/paper/2107.12146/) (2021)
- [Local Extreme Learning Machines and Domain Decomposition for Solving Linear and Nonlinear Partial Differential Equations](https://mlsanity.com/paper/2012.02895/) (2020)
- [Physics-informed neural networks for solving Reynolds-averaged Navierunicodex2013Stokes equations](https://mlsanity.com/paper/2107.10711/) (2021)
- [Physics Informed Extreme Learning Machine (PIELM) -- A rapid method for the numerical solution of partial differential equations](https://mlsanity.com/paper/1907.03507/) (2019)
- [Bayesian Physics-Informed Neural Networks for real-world nonlinear dynamical systems](https://mlsanity.com/paper/2205.08304/) (2022)
- [Learning Functional Priors and Posteriors from Data and Physics](https://mlsanity.com/paper/2106.05863/) (2021)
- [NeuralUQ: A comprehensive library for uncertainty quantification in neural differential equations and operators](https://mlsanity.com/paper/2208.11866/) (2022)
- [Correcting model misspecification in physics-informed neural networks (PINNs)](https://mlsanity.com/paper/2310.10776/) (2023)
- [Discovering and forecasting extreme events via active learning in neural operators](https://mlsanity.com/paper/2204.02488/) (2022)
- [L-HYDRA: Multi-Head Physics-Informed Neural Networks](https://mlsanity.com/paper/2301.02152/) (2023)
- [AI-Aristotle: A Physics-Informed framework for Systems Biology Gray-Box Identification](https://mlsanity.com/paper/2310.01433/) (2023)
- [Uncertainty quantification for noisy inputs-outputs in physics-informed neural networks and neural operators](https://mlsanity.com/paper/2311.11262/) (2023)
- [On Computing the Hyperparameter of Extreme Learning Machines: Algorithm and Application to Computational PDEs, and Comparison with Classical and High-Order Finite Elements](https://mlsanity.com/paper/2110.14121/) (2021)
- [Discovering a reaction-diffusion model for Alzheimer's disease by combining PINNs with symbolic regression](https://mlsanity.com/paper/2307.08107/) (2023)
- [An Extreme Learning Machine-Based Method for Computational PDEs in Higher Dimensions](https://mlsanity.com/paper/2309.07049/) (2023)
- [Parsimonious Physics-Informed Random Projection Neural Networks for Initial-Value Problems of ODEs and index-1 DAEs](https://mlsanity.com/paper/2203.05337/) (2022)
- [RandONet: Shallow-Networks with Random Projections for learning linear and nonlinear operators](https://mlsanity.com/paper/2406.05470/) (2024)
- [Automated generation of 0D and 1D reduced-order models of patient-specific blood flow](https://mlsanity.com/paper/2111.04878/) (2021)

## Built on by (most cited first, 3 of 3)

- [From PINNs to PIKANs: Recent Advances in Physics-Informed Machine Learning](https://mlsanity.com/paper/2410.13228/) (2024)
- [Learning and discovering multiple solutions using physics-informed neural networks with random initialization and deep ensemble](https://mlsanity.com/paper/2503.06320/) (2025)
- [Model synthesis and identifiability analysis of stiff chemical reaction systems with inVAErt networks](https://mlsanity.com/paper/2605.04134/) (2026)

## Abstract (arXiv)

When predicting physical phenomena through simulation, quantification of the total uncertainty due to multiple sources is as crucial as making sure the underlying numerical model is accurate. Possible sources include irreducible aleatoric uncertainty due to noise in the data, epistemic uncertainty induced by insufficient data or inadequate parameterization, and model-form uncertainty related to the use of misspecified model equations. Physics-based regularization interacts in nontrivial ways with aleatoric, epistemic and model-form uncertainty and their combination, and a better understanding of this interaction is needed to improve the predictive performance of physics-informed digital twins that operate under real conditions. With a specific focus on biological and physiological models, this study investigates the decomposition of total uncertainty in the estimation of states and parameters of a differential system simulated with MC X-TFC, a new physics-informed approach for uncertainty quantification based on random projections and Monte-Carlo sampling. MC X-TFC is applied to a six-compartment stiff ODE system, the CVSim-6 model, developed in the context of human physiology. The system is analyzed by progressively removing data while estimating an increasing number of parameters and by investigating total uncertainty under model-form misspecification of non-linear resistance in the pulmonary compartment. In particular, we focus on the interaction between the formulation of the discrepancy term and quantification of model-form uncertainty, and show how additional physics can help in the estimation process. The method demonstrates robustness and efficiency in estimating unknown states and parameters, even with limited, sparse, and noisy data. It also offers great flexibility in integrating data with physics for improved estimation, even in cases of model misspecification.