Title | ||
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COBRAme: A computational framework for genome-scale models of metabolism and gene expression. |
Abstract | ||
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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 a new fundamental understanding 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 functionally identical solutions to previous E. coli ME-models while using 1/6 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. Errors in previous ME-models were also corrected leading to 52 additional genes that must be expressed in IJL1678b-ME to grow aerobically in glucose minimal in silico media. This manuscript outlines the architecture of COBRAme and demonstrates how ME-models can be created, modified, and shared most efficiently using the new software framework. |
Year | DOI | Venue |
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2018 | 10.1371/journal.pcbi.1006302 | PLOS COMPUTATIONAL BIOLOGY |
Field | DocType | Volume |
Genome,Biology,Free variables and bound variables,Theoretical computer science,Proteome,Genetics,Thermotoga maritima,Software framework,Python (programming language),In silico,Computation | Journal | 14 |
Issue | ISSN | Citations |
7 | 1553-734X | 4 |
PageRank | References | Authors |
0.45 | 11 | 8 |
Name | Order | Citations | PageRank |
---|---|---|---|
Colton J Lloyd | 1 | 5 | 2.51 |
Ali Ebrahim | 2 | 60 | 4.31 |
Laurence Yang | 3 | 9 | 2.75 |
Zachary A. King | 4 | 60 | 4.97 |
Edward Catoiu | 5 | 4 | 1.46 |
Edward J. O'Brien | 6 | 4 | 0.79 |
Joanne K. Liu | 7 | 12 | 1.38 |
Bernhard O. Palsson | 8 | 751 | 67.99 |