High−throughput functional curation of cellular electrophysiology models

Abstract

Effective reuse of a quantitative mathematical model requires not just access to curated versions of the model equations, but also an understanding of the functional capabilities of the model, and the advisable scope of its application. To enable this “functional curation” we have developed a simulation environment that provides high-throughput evaluation of a mathematical model’s functional response to an arbitrary user-defined protocol, and optionally compares the results against experimental data. In this study we demonstrate the efficacy of this simulation environment on 31 cardiac electrophysiology cell models using two test cases. The S1–S2 response is evaluated to characterise the models’ restitution curves, and their L-type calcium channel current–voltage curves are evaluated. The significant variation in the response of these models, even when the models represent the same species and temperature, demonstrates the importance of knowing the functional characteristics of a model prior to its reuse. We also discuss the wider implications for this approach, in improving the selection of models for reuse, enabling the identification of models that exhibit particular experimentally observed phenomena, and making the incremental development of models more robust.