Orchestral: a lightweight framework for parallel simulations of cell-cell communication

TL;DR

Orchestral is a scalable, modular framework enabling massively parallel, spatially resolved stochastic simulations of multicellular systems, effectively decoupling intracellular kinetics from cell-cell interactions for use on distributed computing platforms.

Contribution

It introduces a novel operator-splitting based framework that decouples intracellular and intercellular processes, allowing flexible coupling with existing single-cell simulation tools.

Findings

Successfully simulated multicellular Notch-Delta signaling on cloud infrastructure.

Demonstrated high scalability and flexibility of the framework.

Enabled coupling of various single-cell simulation software.

Abstract

We develop a modeling and simulation framework capable of massively parallel simulation of multicellular systems with spatially resolved stochastic kinetics in individual cells. By the use of operator-splitting we decouple the simulation of reaction-diffusion kinetics inside the cells from the simulation of molecular cell-cell interactions occurring on the boundaries between cells. This decoupling leverages the inherent scale separation in the underlying model to enable highly horizontally scalable parallel simulation, suitable for simulation on heterogeneous, distributed computing infrastructures such as public and private clouds. Thanks to its modular structure, our frameworks makes it possible to couple just any existing single-cell simulation software together with any cell signaling simulator. We exemplify the flexibility and scalability of the framework by using the popular single-cell simulation software eGFRD to construct and simulate a multicellular model of Notch-Delta signaling over OpenStack cloud infrastructure provided by the SNIC Science Cloud.