Programming strategy for efficient modeling of dynamics in a population of heterogeneous cells

Abstract

Motivation: Heterogeneity is a ubiquitous property of biological systems. Even in a genetically identical population of a single cell type, cell-to-cell differences are observed. Although the functional behavior of a given population is generally robust, the consequences of heterogeneity are fairly unpredictable. In heterogeneous populations, synchronization of events becomes a cardinal problem-particularly for phase coherence in oscillating systems. Results: The present article presents a novel strategy for construction of large-scale simulation programs of heterogeneous biological entities. The strategy is designed to be tractable, to handle heterogeneity and to handle computational cost issues simultaneously, primarily by writing a generator of the 'model to be simulated'. We apply the strategy to model glycolytic oscillations among thousands of yeast cells coupled through the extracellular medium. The usefulness is illustrated through (i) benchmarking, showing an almost linear relationship between model size and run time, and (ii) analysis of the resulting simulations, showing that contrary to the experimental situation, synchronous oscillations are surprisingly hard to achieve, underpinning the need for tools to study heterogeneity. Thus, we present an efficient strategy to model the biological heterogeneity, neglected by ordinary mean-field models. This tool is well posed to facilitate the elucidation of the physiologically vital problem of synchronization. © 2013 The Author. Published by Oxford University Press. All rights reserved.