title: Principles of proteome allocation are revealed using proteomic data and genome-scale models.
abstract: Integrating omics data to refine or make context-specific models is an active field of constraint-based modeling. Proteomics now cover over 95% of the Escherichia coli proteome by mass. Genome-scale models of Metabolism and macromolecular Expression (ME) compute proteome allocation linked to metabolism and fitness. Using proteomics data, we formulated allocation constraints for key proteome sectors in the ME model. The resulting calibrated model effectively computed the "generalist" (wild-type) E. coli proteome and phenotype across diverse growth environments. Across 15 growth conditions, prediction errors for growth rate and metabolic fluxes were 69% and 14% lower, respectively. The sector-constrained ME model thus represents a generalist ME model reflecting both growth rate maximization and "hedging" against uncertain environments and stresses, as indicated by significant enrichment of these sectors for the general stress response sigma factor σS. Finally, the sector constraints represent a general formalism for integrating omics data from any experimental condition into constraint-based ME models. The constraints can be fine-grained (individual proteins) or coarse-grained (functionally-related protein groups) as demonstrated here. This flexible formalism provides an accessible approach for narrowing the gap between the complexity captured by omics data and governing principles of proteome allocation described by systems-level models.
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.|Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, California, USA.
authors.forename: James T
authors.initials: JT
authors.lastname: Yurkovich
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.
authors.forename: Colton J
authors.initials: CJ
authors.lastname: Lloyd
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Ebrahim
authors.affiliation: Department of Management Science and Engineering, Stanford University, Stanford, California, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Saunders
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.|Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, California, USA.|Novo Nordisk Foundation Center for Biosustainability, The Technical University of Denmark, Hørsholm, Denmark.
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Palsson
mesh_terms: D003198:Computer Simulation; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D016680:Genome, Bacterial; D008957:Models, Genetic; D020543:Proteome / Q000235:genetics* / Q000378:metabolism; D040901:Proteomics
chemical_list: D020543:Proteome