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Calibration, uncertainty and credibility

How far a model's predictions can be trusted: emulators, sensitivity analysis and calibration that state what the data can identify, and verification of the simulators themselves.

Calibrating a passive mechanics model of the left atrium to its deformation measured from gated CT, by comparing the end-systolic volume and the global and regional displacements derived from the images with those simulated and emulated. Global sensitivity analysis identifies the parameters that matter, history matching rules out, in waves, the parameter values that cannot reproduce the image-derived outputs, and Markov chain Monte Carlo approximates the posterior distribution and its maximum a posteriori estimate. Adapted from Figure 1 of Baptiste et al. (2025), PLoS Computational Biology, under CC BY 4.0.
Calibrating a passive mechanics model of the left atrium to its deformation measured from gated CT, by comparing the end-systolic volume and the global and regional displacements derived from the images with those simulated and emulated. Global sensitivity analysis identifies the parameters that matter, history matching rules out, in waves, the parameter values that cannot reproduce the image-derived outputs, and Markov chain Monte Carlo approximates the posterior distribution and its maximum a posteriori estimate. Adapted from Figure 1 of Baptiste et al. (2025), PLoS Computational Biology, under CC BY 4.0.

A model tied to a patient has to be calibrated to limited, noisy data, so the work is as much statistical as physiological. Whole-heart simulations are expensive to run, so Gaussian process emulators and reduced-order models stand in for the simulator, which makes global sensitivity analysis, history matching and Bayesian calibration affordable. These establish which parameters the measurements can identify, and how much uncertainty remains in anything the model then predicts. Emulators that share what they learn across a cohort of digital twins cut the cost of emulating the cohort by more than half, and models of rat and human myocytes carry drug effects measured in rats over to people.

Credibility is studied in its own right: how to assess it for patient-specific models and for in silico trials of medical devices, and how it is balanced against a model’s complexity. Benchmark problems test whether different simulators give the same answer to the same problem.

Recent papers

  1. Tiffany M.G. Baptiste, Cristobal Rodero, Charles P. Sillett, Marina Strocchi, Christopher W. Lanyon, …, Angela W. C. Lee, José Alonso Solís-Lemus, Caroline H. Roney, …, Steven A. Niederer, PLoS Computational Biology, 2025

    Regional heterogeneity in left atrial stiffness impacts passive deformation in a cohort of patient-specific models

  2. Cristobal Rodero, Steven A. Niederer, Proceedings of the National Academy of Sciences, 2025

    Striking the balance: Complexity, simplicity, and credibility in mathematical biology

  3. Shahrokh Rahmani, Jim Pouliopoulos, Angela Lee, Rosie Kate Barrows, Marina Strocchi, Cristobal Rodero, Abdul Qayyum, Caroline H. Roney, …, Steven Niederer, Computing in cardiology, 2024

    Cardiac Sensitivities to Biomechanical Changes in a Chronic Alcoholic Heart: A Case Study Using 3-Dimensional Electro-Mechanical Heart Modelling

  4. Matteo Salvador, Marina Strocchi, Francesco Regazzoni, …, Steven A. Niederer, …, npj Digital Medicine, 2024

    Whole-heart electromechanical simulations using Latent Neural Ordinary Differential Equations

  5. Hamed Keramati, Adelaide de Vecchi, …, Steven A. Niederer, PLoS ONE, 2023

    Using Gaussian process for velocity reconstruction after coronary stenosis applicable in positron emission particle tracking: An in-silico study

  6. Marina Strocchi, Stefano Longobardi, Christoph M. Augustin, …, Steven A. Niederer, PLoS Computational Biology, 2023

    Cell to whole organ global sensitivity analysis on a four-chamber heart electromechanics model using Gaussian processes emulators

  7. Cesare Corrado, Caroline H. Roney, Orod Razeghi, Josè Alonso Solís Lemus, Sam Coveney, …, Steven A. Niederer, Computers in Biology and Medicine, 2023

    Quantifying the impact of shape uncertainty on predicted arrhythmias