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  1. Abstract Motivation

    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.

    Results

    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.

    Availability and implementation

    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 information

    Supplementary data are available at Bioinformatics online.

     
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  2. Social hierarchies are ubiquitous in social species and profoundly influence physiology and behavior. Androgens like testosterone have been strongly linked to social status, yet the molecular mechanisms regulating social status are not known. The African cichlid fishAstatotilapia burtoniis a powerful model species for elucidating the role of androgens in social status given their rich social hierarchy and genetic tractability. DominantA. burtonimales possess large testes and bright coloration and perform aggressive and reproductive behaviors while nondominant males do not. Social status inA. burtoniis in flux, however, as males alter their status depending on the social environment. Due to a teleost-specific whole-genome duplication,A. burtonipossess two androgen receptor (AR) paralogs,ARαandARβ, providing a unique opportunity to disentangle the role of gene duplication in the evolution of social systems. Here, we used CRISPR/Cas9 gene editing to generate AR mutantA. burtoniand performed a suite of experiments to interrogate the mechanistic basis of social dominance. We find thatARβ,but notARα, is required for testes growth and bright coloration, whileARα, but notARβ, is required for the performance of reproductive behavior and aggressive displays. Both receptors are required to reduce flees from females and either AR is sufficient for attacking males. Thus, social status inA. burtoniis inordinately dissociable and under the modular control of two AR paralogs. This type of nonredundancy may be important in facilitating social plasticity inA. burtoniand other species whose social status relies on social experience.

     
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