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Title: Principles of proteome allocation are revealed using proteomic data and genome-scale models

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. Furthermore, 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.
 [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [3]
  1. Univ. of California, San Diego, La Jolla, CA (United States)
  2. Stanford Univ., Stanford, CA (United States)
  3. Univ. of California, San Diego, La Jolla, CA (United States); The Technical Univ. of Denmark, Horsholm (Denmark)
Publication Date:
Grant/Contract Number:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 6; Journal Issue: 1; Journal ID: ISSN 2045-2322
Nature Publishing Group
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org:
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; biochemical networks; computer modelling
OSTI Identifier: