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. 2016 Jan 19;110(2):292-300.
doi: 10.1016/j.bpj.2015.12.012.

The Cardiac Electrophysiology Web Lab

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Free PMC article

The Cardiac Electrophysiology Web Lab

Jonathan Cooper et al. Biophys J. .
Free PMC article

Abstract

Computational modeling of cardiac cellular electrophysiology has a long history, and many models are now available for different species, cell types, and experimental preparations. This success brings with it a challenge: how do we assess and compare the underlying hypotheses and emergent behaviors so that we can choose a model as a suitable basis for a new study or to characterize how a particular model behaves in different scenarios? We have created an online resource for the characterization and comparison of electrophysiological cell models in a wide range of experimental scenarios. The details of the mathematical model (quantitative assumptions and hypotheses formulated as ordinary differential equations) are separated from the experimental protocol being simulated. Each model and protocol is then encoded in computer-readable formats. A simulation tool runs virtual experiments on models encoded in CellML, and a website (https://chaste.cs.ox.ac.uk/WebLab) provides a friendly interface, allowing users to store and compare results. The system currently contains a sample of 36 models and 23 protocols, including current-voltage curve generation, action potential properties under steady pacing at different rates, restitution properties, block of particular channels, and hypo-/hyperkalemia. This resource is publicly available, open source, and free, and we invite the community to use it and become involved in future developments. Investigators interested in comparing competing hypotheses using models can make a more informed decision, and those developing new models can upload them for easy evaluation under the existing protocols, and even add their own protocols.

Figures

Figure 1
Figure 1
Schematic of the technical infrastructure underlying our website. In the state-of-the-art model repositories, each available model description is actually a model of a particular experimental setup (generally 1 Hz pacing in cardiac AP models). In our database, models represent a biological system, and experimental protocols are described separately and may be applied to any model. Experimental data will be directly comparable with the results of certain protocols. To see this figure in color, go online.
Figure 2
Figure 2
Overview of the virtual experiments available in our system at the time of this writing (see https://chaste.cs.ox.ac.uk/FunctionalCuration/db.html for the current status). Each square represents the stored results of a single virtual experiment, color coded according to status. Green indicates that the protocol ran to completion, orange that it did not complete but some of the expected graphs are nevertheless available (so only a subset of the simulations and/or postprocessing failed), red that no graphs are available, and gray that the model and protocol are incompatible (i.e., the model does not contain some biological feature probed by the protocol). Shades of blue indicate a queued or running experiment (no examples shown). Note, therefore, that the colors do not indicate model correctness in any sense. To see this figure in color, go online.
Figure 3
Figure 3
1 Hz (top) and 2 Hz (bottom) steady-pacing AP waveforms for a selection of human ventricular cell models. See https://chaste.cs.ox.ac.uk/q/2015/fc/fig3a and https://chaste.cs.ox.ac.uk/q/2015/fc/fig3b for the Web Lab originals. To see this figure in color, go online.
Figure 4
Figure 4
Restitution curves for the O’Hara 2011 model epi- and endocardial variants. Variation in APD at 90% repolarization is shown for the S1-S2 protocol with the initial stimulus interval S1 set to 1000 ms, and for steady-state restitution (in which two paces are analyzed and plotted as two lines, to show fork or alternans at short rates, visible in the endocardial variant). This demonstrates the Web Lab’s ability to run complex protocols with intricate postprocessing. See https://chaste.cs.ox.ac.uk/q/2015/fc/fig4 for the Web Lab original. To see this figure in color, go online.
Figure 5
Figure 5
Effect of blockade of NCX on steady-state APD in some human ventricular cell models. Note that across 0–80% NCX block, some models predict little effect (<5% change), whereas others predict 20% prolongation and still others predict 20% shortening. At 80–100% block, the results vary dramatically, with models predicting effects ranging from 45% prolongation to 20% shortening compared with control. See https://chaste.cs.ox.ac.uk/q/2015/fc/fig5 for the Web Lab original. To see this figure in color, go online.
Figure 6
Figure 6
Effect of examining behavior before and after steady state is reached, for 0% (dashed line), 25%, 50%, 75%, and 100% block of the rapid delayed rectifier potassium current (IKr) in the Priebe 1998 model. Left: after just one pace at each degree of IKr block, the results are the same as those shown in Priebe and Beuckelmann (39). Right: the same model after 10,000 paces for each degree of IKr block as shown in the Web Lab. Note that even the control AP varies considerably, and is much longer in the steady-state case.

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