TY - JOUR T1 - COBRAme: A Computational Framework for Genome-Scale Models of Metabolism and Gene Expression JF - bioRxiv DO - 10.1101/106559 SP - 106559 AU - Colton J. Lloyd AU - Ali Ebrahim AU - Laurence Yang AU - Zachary King AU - Edward Catoiu AU - Edward J. O’Brien AU - Joanne K. Liu AU - Bernhard O. Palsson Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/10/31/106559.abstract N2 - Genome-scale models of metabolism and macromolecular expression (ME-models) explicitly compute the optimal proteome composition of a growing cell. ME-models expand upon the well-established genome-scale models of metabolism (M-models), and they enable new and exciting insights that are fundamental to understanding the basis of cellular growth. ME-models have increased predictive capabilities and accuracy due to their inclusion of the biosynthetic costs for the machinery of life, but they come with a significant increase in model size and complexity. This challenge results in models which are both difficult to compute and challenging to understand conceptually. As a result, ME-models exist for only two organisms (Escherichia coli and Thermotoga maritima) and are still used by relatively few researchers. To address these challenges, we have developed a new software framework called COBRAme for building and simulating ME-models. It is coded in Python and built on COBRApy, a popular platform for using M-models. COBRAme streamlines computation and analysis of ME-models. It provides tools to simplify constructing and editing ME-models to enable ME-model reconstructions for new organisms. We used COBRAme to reconstruct a condensed E. coli ME-model called iJL1678b-ME. This reformulated model gives virtually identical solutions to previous E. coli ME-models while using ¼ the number of free variables and solving in less than 10 minutes, a marked improvement over the 6 hour solve time of previous ME-model formulations. This manuscript outlines the architecture of COBRAme and demonstrates how ME-models can be reconstructed and edited most efficiently using the software. ER -