  Genome-scale stoichiometric modeling of metabolism has become a standard
systems biology tool for modeling cellular physiology and growth. Extensions of
this approach are also emerging as a valuable avenue for predicting,
understanding and designing microbial communities. COMETS (Computation Of
Microbial Ecosystems in Time and Space) was initially developed as an extension
of dynamic flux balance analysis, which incorporates cellular and molecular
diffusion, enabling simulations of multiple microbial species in spatially
structured environments. Here we describe how to best use and apply the most
recent version of this platform, COMETS 2, which incorporates a more accurate
biophysical model of microbial biomass expansion upon growth, as well as
several new biological simulation modules, including evolutionary dynamics and
extracellular enzyme activity. COMETS 2 provides user-friendly Python and
MATLAB interfaces compatible with the well-established COBRA models and
methods, and comprehensive documentation and tutorials, facilitating the use of
COMETS for researchers at all levels of expertise with metabolic simulations.
This protocol provides a detailed guideline for installing, testing and
applying COMETS 2 to different scenarios, with broad applicability to microbial
communities across biomes and scales.
