Vivarium: an interface and engine for integrative multiscale modeling in computational biology.

Eran Agmon,Christopher J Skalnik,Ryan K Spangler,Jerry H Morrison,Markus W Covert,William Poole,Shayn M Peirce,Alfonso Valencia

doi:10.1093/bioinformatics/btac049

Abstract

This article introduces Vivarium-software born of the idea that it should be as easy as possible for computational biologists to define any imaginable mechanistic model, combine it with existing models and execute them together as an integrated multiscale model. Integrative multiscale modeling confronts the complexity of biology by combining heterogeneous datasets and diverse modeling strategies into unified representations. These integrated models are then run to simulate how the hypothesized mechanisms operate as a whole. But building such models has been a labor-intensive process that requires many contributors, and they are still primarily developed on a case-by-case basis with each project starting anew. New software tools that streamline the integrative modeling effort and facilitate collaboration are therefore essential for future computational biologists. Vivarium is a software tool for building integrative multiscale models. It provides an interface that makes individual models into modules that can be wired together in large composite models, parallelized across multiple CPUs and run with Vivarium's discrete-event simulation engine. Vivarium's utility is demonstrated by building composite models that combine several modeling frameworks: agent-based models, ordinary differential equations, stochastic reaction systems, constraint-based models, solid-body physics and spatial diffusion. This demonstrates just the beginning of what is possible-Vivarium will be able to support future efforts that integrate many more types of models and at many more biological scales. The specific models, simulation pipelines and notebooks developed for this article are all available at the vivarium-notebooks repository: https://github.com/vivarium-collective/vivarium-notebooks. Vivarium-core is available at https://github.com/vivarium-collective/vivarium-core, and has been released on Python Package Index. The Vivarium Collective (https://vivarium-collective.github.io) is a repository of freely available Vivarium processes and composites, including the processes used in Section 3. Supplementary Materials provide with an extensive methodology section, with several code listings that demonstrate the basic interfaces. Supplementary data are available at Bioinformatics online.

Highlights

Mechanistic models in computational biology have deepened our understanding of diverse domains of biological function, from the macromolecular structure and dynamics of a bacterial cytoplasm with atomistic models [5], the lysis/lysogeny switch of bacteriophage lambda with a stochastic models [6], bacterial growth in different conditions with constraint-based metabolic models [7], and cell-based models of quorum sensing in bacterial populations [8]
This paper introduces Vivarium – software born of the idea that it should be as easy as possible for computational biologists to define any mechanistic model, combine it with existing models, and execute them together as an integrated multiscale model
We developed a Vivarium process that provides a wrapper around COBRApy [20], an API which can be initialized with genome-scale metabolic flux models [39]

Summary

Introduction

Our understanding of biological phenomena stands to be dramatically improved if we can adequately represent the underlying systems, mechanisms, and interactions that influence their behavior over time. Mechanistic models in computational biology have deepened our understanding of diverse domains of biological function, from the macromolecular structure and dynamics of a bacterial cytoplasm with atomistic models [5], the lysis/lysogeny switch of bacteriophage lambda with a stochastic models [6], bacterial growth in different conditions with constraint-based metabolic models [7], and cell-based models of quorum sensing in bacterial populations [8] Such models generally target a mechanism in isolation, with a single class of mathematical representation, and focus on a narrow range of resulting behavior.

Vivarium overview

Multi-paradigm composites

Individual paradigms

Model integration and simulation results

Discussion

Conclusion