Bayesian inference for fitting cardiac models to experiments: estimating parameter distributions using Hamiltonian Monte Carlo and approximate Bayesian computation.

Alejandro Nieto Ramos, Flavio H Fenton, Elizabeth M Cherry
Author Information
  1. Alejandro Nieto Ramos: School of Mathematical Sciences, Rochester Institute of Technology, 1 Lomb Memorial Drive, 14623, Rochester, NY, USA.
  2. Flavio H Fenton: School of Physics, Georgia Institute of Technology, 837 State Street NW, 30332, Atlanta, GA, USA.
  3. Elizabeth M Cherry: School of Computational Science and Engineering, Georgia Institute of Technology, 756 West Peachtree Street, 30308, Atlanta, GA, USA. elizabeth.cherry@gatech.edu. ORCID

Abstract

Customization of cardiac action potential models has become increasingly important with the recognition of patient-specific models and virtual patient cohorts as valuable predictive tools. Nevertheless, developing customized models by fitting parameters to data poses technical and methodological challenges: despite noise and variability associated with real-world datasets, traditional optimization methods produce a single "best-fit" set of parameter values. Bayesian estimation methods seek distributions of parameter values given the data by obtaining samples from the target distribution, but in practice widely known Bayesian algorithms like Markov chain Monte Carlo tend to be computationally inefficient and scale poorly with the dimensionality of parameter space. In this paper, we consider two computationally efficient Bayesian approaches: the Hamiltonian Monte Carlo (HMC) algorithm and the approximate Bayesian computation sequential Monte Carlo (ABC-SMC) algorithm. We find that both methods successfully identify distributions of model parameters for two cardiac action potential models using model-derived synthetic data and an experimental dataset from a zebrafish heart. Although both methods appear to converge to the same distribution family and are computationally efficient, HMC generally finds narrower marginal distributions, while ABC-SMC is less sensitive to the algorithmic settings including the prior distribution.

Keywords

References

  1. Fenton FH, Cherry EM (2008) Models of cardiac cell. Scholarpedia 3(8):1868
  2. Groenendaal W, Ortega FA, Kherlopian AR, Zygmunt AC, Krogh-Madsen T, Christini DJ (2015) Cell-specific cardiac electrophysiology models. PLoS Comput Biol 11(4):1004242. https://doi.org/10.1371/journal.pcbi.1004242 [DOI: 10.1371/journal.pcbi.1004242]
  3. Boyle PM, Zghaib T, Zahid S, Ali RL, Deng D, Franceschi WH, Hakim JB, Murphy MJ, Prakosa A, Zimmerman SL, Ashikaga H, Marine JE, Kolandaivelu A, Nazarian S, Spragg DD, Calkins H, Trayanova NA (2019) Computationally guided personalized targeted ablation of persistent atrial fibrillation. Nat Biomed Eng 3(11):870–879 [DOI: 10.1038/s41551-019-0437-9]
  4. Niederer SA, Aboelkassem Y, Cantwell CD, Corrado C, Coveney S, Cherry EM, Delhaas T, Fenton FH, Panfilov AV, Pathmanathan P, Plank G, Riabiz M, Roney CH, dos Santos RW, Wang L (2020) Creation and application of virtual patient cohorts of heart models. Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 378(2173):20190558. https://doi.org/10.1098/rsta.2019.0558 [DOI: 10.1098/rsta.2019.0558]
  5. Dokos S, Lovell NH (2004) Parameter estimation in cardiac ionic models. Prog Biophys Mol Biol 85(2):407–431. https://doi.org/10.1016/j.pbiomolbio.2004.02.002 [DOI: 10.1016/j.pbiomolbio.2004.02.002]
  6. Bueno-Orovio A, Cherry EM, Fenton FH (2008) Minimal model for human ventricular action potentials in tissue. J Theor Biol 253(3):544–560. https://doi.org/10.1016/j.jtbi.2008.03.029 [DOI: 10.1016/j.jtbi.2008.03.029]
  7. Syed Z, Vigmond E, Nattel S, Leon LJ (2005) Atrial cell action potential parameter fitting using genetic algorithms. Med Biol Eng Compu 43(5):561–571 [DOI: 10.1007/BF02351029]
  8. Bot CT, Kherlopian AR, Ortega FA, Christini DJ, Krogh-Madsen T (2012) Rapid genetic algorithm optimization of a mouse computational model: benefits for anthropomorphization of neonatal mouse cardiomyocytes. Front Physiol 3:421. https://doi.org/10.3389/fphys.2012.00421 [DOI: 10.3389/fphys.2012.00421]
  9. Cairns DI, Fenton FH, Cherry EM (2017) Efficient parameterization of cardiac action potential models using a genetic algorithm. Chaos 27(9):093922. https://doi.org/10.1063/1.5000354 [DOI: 10.1063/1.5000354]
  10. Loewe A, Wilhelms M, Schmid J, Krause MJ, Fischer F, Thomas D, Scholz EP, Dössel O, Seemann G (2015) Parameter estimation of ion current formulations requires hybrid optimization approach to be both accurate and reliable. Front Bioeng Biotechnol 3:209. https://doi.org/10.3389/fbioe.2015.00209 [DOI: 10.3389/fbioe.2015.00209]
  11. Coveney S, Clayton RH (2018) Fitting two human atrial cell models to experimental data using Bayesian history matching. Prog Biophys Mol Biol 139:43–58. https://doi.org/10.1016/j.pbiomolbio.2018.08.001 [DOI: 10.1016/j.pbiomolbio.2018.08.001]
  12. Zaman MS, Dhamala J, Bajracharya P, Sapp JL, Horácek BM, Wu KC, Trayanova NA, Wang L (2021) Fast posterior estimation of cardiac electrophysiological model parameters via Bayesian active learning. Frontiers in Physiology 12: 740306. https://doi.org/10.3389/fphys.2021.740306. Accessed 2022-04-15
  13. Siekmann I, Wagner LE, Yule D, Fox C, Bryant D, Crampin EJ, Sneyd J (2011) MCMC estimation of Markov models for ion channels. Biophys J 100(8):1919–1929. https://doi.org/10.1016/j.bpj.2011.02.059 [DOI: 10.1016/j.bpj.2011.02.059]
  14. Pathmanathan P, Shotwell MS, Gavaghan DJ, Cordeiro JM, Gray RA (2015) Uncertainty quantification of fast sodium current steady-state inactivation for multi-scale models of cardiac electrophysiology. Prog Biophys Mol Biol 117(1):4–18. https://doi.org/10.1016/j.pbiomolbio.2015.01.008 [DOI: 10.1016/j.pbiomolbio.2015.01.008]
  15. Daly AC, Gavaghan DJ, Holmes C, Cooper J (2015) Hodgkin-Huxley revisited: reparametrization and identifiability analysis of the classic action potential model with approximate Bayesian methods. Royal Society Open Science 2(12):150499. https://doi.org/10.1098/rsos.150499 [DOI: 10.1098/rsos.150499]
  16. Neal, R.M.: MCMC using Hamiltonian dynamics. In: Handbook of Markov chain Monte Carlo. Chapman & Hall/CRC Handb. Mod. Stat. Methods, pp. 113–162 (2011)
  17. Vernon I, Liu J, Goldstein M, Rowe J, Topping J, Lindsey K (2018) Bayesian uncertainty analysis for complex systems biology models: emulation, global parameter searches and evaluation of gene functions. BMC Syst Biol 12(1):1. https://doi.org/10.1186/s12918-017-0484-3 [DOI: 10.1186/s12918-017-0484-3]
  18. Del Moral P, Doucet A, Jasra A (2006) Sequential Monte Carlo samplers. Journal of the Royal Statistical Society. Series B (Statistical Methodology) 68(3): 411–436
  19. Toni T, Welch D, Strelkowa N, Ipsen A, Stumpf MPH (2009) Approximate Bayesian computation scheme for parameter inference and model selection in dynamical systems. J R Soc Interface 6(31):187–202. https://doi.org/10.1098/rsif.2008.0172 [DOI: 10.1098/rsif.2008.0172]
  20. Del Moral P, Doucet A, Jasra A (2012) An adaptive sequential Monte Carlo method for approximate Bayesian computation. Stat Comput 22(5):1009–1020. https://doi.org/10.1007/s11222-011-9271-y [DOI: 10.1007/s11222-011-9271-y]
  21. O’Hara T, Virág L, Varró A, Rudy Y (2011) Simulation of the undiseased human cardiac ventricular action potential: model formulation and experimental validation. PLoS Comput Biol 7(5):1002061 [DOI: 10.1371/journal.pcbi.1002061]
  22. Daly AC, Cooper J, Gavaghan DJ, Holmes C (2017) Comparing two sequential Monte Carlo samplers for exact and approximate Bayesian inference on biological models. J R Soc Interface 14(134):20170340. https://doi.org/10.1098/rsif.2017.0340 [DOI: 10.1098/rsif.2017.0340]
  23. Duane S, Kennedy AD, Pendleton BJ, Roweth D (1987) Hybrid Monte Carlo. Phys Lett B 195(2):216–222. https://doi.org/10.1016/0370-2693(87)91197-X [DOI: 10.1016/0370-2693(87)91197-X]
  24. Monnahan CC, Thorson JT, Branch TA (2017) Faster estimation of Bayesian models in ecology using Hamiltonian Monte Carlo. Methods Ecol Evol 8(3):339–348. https://doi.org/10.1111/2041-210X.12681 [DOI: 10.1111/2041-210X.12681]
  25. Margossian CC, Zhang Y, Gillespie WR (2021) Flexible and efficient Bayesian pharmacometrics modeling using Stan and Torsten, part I. arXiv:2109.10184 [stat]
  26. Nieto Ramos A, Herndon CJ, Fenton FH, Cherry EM (2021) Quantifying distributions of parameters for cardiac action potential models using the Hamiltonian Monte Carlo method. Computing in Cardiology 48:9662836–196628364
  27. Mitchell CC, Schaeffer DG (2003) A two-current model for the dynamics of cardiac membrane. Bull Math Biol 65(5):767–793. https://doi.org/10.1016/S0092-8240(03)00041-7 [DOI: 10.1016/S0092-8240(03)00041-7]
  28. Fenton F, Karma A (1998) Vortex dynamics in three-dimensional continuous myocardium with fiber rotation: filament instability and fibrillation. Chaos 8(1):20–47. https://doi.org/10.1063/1.166311 [DOI: 10.1063/1.166311]
  29. Fenton FH, Cherry EM, Hastings HM, Evans SJ (2002) Multiple mechanisms of spiral wave breakup in a model of cardiac electrical activity. Chaos 12(3):852–892. https://doi.org/10.1063/1.1504242 [DOI: 10.1063/1.1504242]
  30. Gamerman D, Lopes HF (2006) Markov chain Monte Carlo: stochastic simulation for Bayesian inference, Second Edition
  31. Marin J-M, Pudlo P, Robert CP, Ryder RJ (2012) Approximate Bayesian computational methods. Stat Comput 22(6):1167–1180. https://doi.org/10.1007/s11222-011-9288-2 [DOI: 10.1007/s11222-011-9288-2]
  32. Betancourt M (2018) A conceptual introduction to Hamiltonian Monte Carlo. arXiv:1701.02434 [stat]
  33. Hoffman MD, Gelman A (2014) The No-U-turn sampler: adaptively setting path lengths in Hamiltonian Monte Carlo. J Mach Learn Res 15(1):1593–1623
  34. Carpenter B, Gelman A, Hoffman MD, Lee D, Goodrich B, Betancourt M, Brubaker M, Guo J, Li P, Riddell A (2017) Stan: a probabilistic programming language. J Stat Softw 76:1–32. https://doi.org/10.18637/jss.v076.i01 [DOI: 10.18637/jss.v076.i01]
  35. Stan Development Team (2022) Stan modeling language users guide and reference manual, version 2.29. //mc-stan.org/
  36. Gelman A, Carlin JB, Stern HS, Dunson DB, Vehtari A, Rubin DB (2013) Bayesian data analysis, 3rd edition edn. Chapman and Hall/CRC
  37. Vehtari A, Gelman A, Simpson D, Carpenter B, Bürkner P-C (2021) Rank-normalization, folding, and localization: an improved [Formula: see text] for assessing convergence of MCMC. Bayesian Analysis 16(2). https://doi.org/10.1214/20-BA1221
  38. Chicco D, Warrens MJ, Jurman G (2021) The coefficient of determination R-squared is more informative than SMAPE, MAE, MAPE, MSE and RMSE in regression analysis evaluation. PeerJ Computer Science 7:623. https://doi.org/10.7717/peerj-cs.623 [DOI: 10.7717/peerj-cs.623]
  39. Shahi S, Marcotte CD, Herndon CJ, Fenton FH, Shiferaw Y, Cherry EM (2021) Long-time prediction of arrhythmic cardiac action potentials using recurrent neural networks and reservoir computing. Frontiers in physiology 12
  40. Whittaker DG, Clerx M, Lei CL, Christini DJ, Mirams GR (2020) Calibration of ionic and cellular cardiac electrophysiology models. Wiley Interdisciplinary Reviews: Systems Biology and Medicine 12(4):1482
  41. Johnstone RH, Chang ET, Bardenet R, De Boer TP, Gavaghan DJ, Pathmanathan P, Clayton RH, Mirams GR (2016) Uncertainty and variability in models of the cardiac action potential: can we build trustworthy models? J Mol Cell Cardiol 96:49–62 [DOI: 10.1016/j.yjmcc.2015.11.018]
  42. Britton OJ, Bueno-Orovio A, Van Ammel K, Lu HR, Towart R, Gallacher DJ, Rodriguez B (2013) Experimentally calibrated population of models predicts and explains intersubject variability in cardiac cellular electrophysiology. Proc Natl Acad Sci USA 110(23):2098–2105. https://doi.org/10.1073/pnas.1304382110 [DOI: 10.1073/pnas.1304382110]
  43. Csercsik D, Hangos KM, Szederkényi G (2012) Identifiability analysis and parameter estimation of a single Hodgkin-Huxley type voltage dependent ion channel under voltage step measurement conditions. Neurocomputing 77(1):178–188. https://doi.org/10.1016/j.neucom.2011.09.006 [DOI: 10.1016/j.neucom.2011.09.006]
  44. Shotwell MS, Gray RA (2016) Estimability analysis and optimal design in dynamic multi-scale models of cardiac electrophysiology. J Agric Biol Environ Stat 21(2):261–276. https://doi.org/10.1007/s13253-016-0244-7 [DOI: 10.1007/s13253-016-0244-7]
  45. Daly AC, Gavaghan D, Cooper J, Tavener S (2018) Inference-based assessment of parameter identifiability in nonlinear biological models. J R Soc Interface 15(144):20180318. https://doi.org/10.1098/rsif.2018.0318 [DOI: 10.1098/rsif.2018.0318]
  46. Chang KC, Dutta S, Mirams GR, Beattie KA, Sheng J, Tran PN, Wu M, Wu WW, Colatsky T, Strauss DG, Li Z (2017) Uncertainty quantification reveals the importance of data variability and experimental design considerations for in silico proarrhythmia risk assessment. Front Physiol 8:917. https://doi.org/10.3389/fphys.2017.00917 [DOI: 10.3389/fphys.2017.00917]

Grants

  1. CNS-2028677/National Science Foundation
  2. CMMI-1762553/National Science Foundation
  3. 1R01HL143450/NIH HHS
  4. 1R01HL143450/NIH HHS

MeSH Term

Animals
Bayes Theorem
Zebrafish
Algorithms
Monte Carlo Method
Markov Chains

Word Cloud

Created with Highcharts 10.0.0BayesianmodelsmethodsparameterdistributionsMonteCarlocardiacactionpotentialdatadistributioncomputationallymodelfittingparametersvaluestwoefficientHamiltonianHMCalgorithmapproximatecomputationABC-SMCusingCustomizationbecomeincreasinglyimportantrecognitionpatient-specificvirtualpatientcohortsvaluablepredictivetoolsNeverthelessdevelopingcustomizedposestechnicalmethodologicalchallenges:despitenoisevariabilityassociatedreal-worlddatasetstraditionaloptimizationproducesingle"best-fit"setestimationseekgivenobtainingsamplestargetpracticewidelyknownalgorithmslikeMarkovchaintendinefficientscalepoorlydimensionalityspacepaperconsiderapproaches:sequentialfindsuccessfullyidentifymodel-derivedsyntheticexperimentaldatasetzebrafishheartAlthoughappearconvergefamilygenerallyfindsnarrowermarginallesssensitivealgorithmicsettingsincludingpriorinferenceexperiments:estimatingAlternansCardiacFenton-KarmaMitchell-SchaefferStatisticalcomputing

Similar Articles

Cited By (2)