PMID: 25502413
OWN: NLM
STAT: MEDLINE
DA: 20141216
DCOM: 20151001
LR: 20170220
IS: 1932-6203 (Electronic) 1932-6203 (Linking)
VI: 9
IP: 12
DP: 2014
TI: Predicting growth conditions from internal metabolic fluxes in an in-silico model of E. coli.
PG: e114608
LID: 10.1371/journal.pone.0114608 [doi]
AB: A widely studied problem in systems biology is to predict bacterial phenotype from growth conditions, using mechanistic models such as flux balance analysis (FBA). However, the inverse prediction of growth conditions from phenotype is rarely considered. Here we develop a computational framework to carry out this inverse prediction on a computational model of bacterial metabolism. We use FBA to calculate bacterial phenotypes from growth conditions in E. coli, and then we assess how accurately we can predict the original growth conditions from the phenotypes. Prediction is carried out via regularized multinomial regression. Our analysis provides several important physiological and statistical insights. First, we show that by analyzing metabolic end products we can consistently predict growth conditions. Second, prediction is reliable even in the presence of small amounts of impurities. Third, flux through a relatively small number of reactions per growth source ( approximately 10) is sufficient for accurate prediction. Fourth, combining the predictions from two separate models, one trained only on carbon sources and one only on nitrogen sources, performs better than models trained to perform joint prediction. Finally, that separate predictions perform better than a more sophisticated joint prediction scheme suggests that carbon and nitrogen utilization pathways, despite jointly affecting cellular growth, may be fairly decoupled in terms of their dependence on specific assortments of molecular precursors.
FAU: ['Sridhara, Viswanadham', 'Meyer, Austin G', 'Rai, Piyush', 'Barrick, Jeffrey E', 'Ravikumar, Pradeep', 'Segre, Daniel', 'Wilke, Claus O']
AU: ['Sridhara V', 'Meyer AG', 'Rai P', 'Barrick JE', 'Ravikumar P', 'Segre D', 'Wilke CO']
AD: Center for Computational Biology and Bioinformatics, The University of Texas at Austin, Austin, Texas, United States of America. Center for Computational Biology and Bioinformatics, The University of Texas at Austin, Austin, Texas, United States of America; Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, United States of America. Department of Computer Science, The University of Texas at Austin, Austin, Texas, United States of America. Center for Computational Biology and Bioinformatics, The University of Texas at Austin, Austin, Texas, United States of America; Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, United States of America; Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, Texas, United States of America; Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, United States of America. Department of Computer Science, The University of Texas at Austin, Austin, Texas, United States of America. Department of Biology and Bioinformatics Program, Boston University, Boston, Massachusetts, United States of America. Center for Computational Biology and Bioinformatics, The University of Texas at Austin, Austin, Texas, United States of America; Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, United States of America; Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, Texas, United States of America; Department of Integrative Biology, The University of Texas at Austin, Austin, Texas, United States of America.
LA: ['eng']
PT: ['Journal Article', "Research Support, Non-U.S. Gov't"]
DEP: 20141212
PL: United States
TA: PLoS One
JT: PloS one
JID: 101285081
RN: ['7440-44-0 (Carbon)', 'N762921K75 (Nitrogen)']
SB: IM
MH: ['Carbon/metabolism', '*Computer Simulation', 'Escherichia coli/cytology/*growth & development/*metabolism', '*Metabolic Flux Analysis', '*Models, Biological', 'Nitrogen/metabolism']
PMC: PMC4264753
OID: ['NLM: PMC4264753']
EDAT: 2014/12/17 06:00
MHDA: 2015/10/02 06:00
CRDT: ['2014/12/16 06:00']
PHST: ['2014/06/24 [received]', '2014/11/11 [accepted]']
AID: ['10.1371/journal.pone.0114608 [doi]', 'PONE-D-14-28270 [pii]']
PST: epublish
SO: PLoS One. 2014 Dec 12;9(12):e114608. doi: 10.1371/journal.pone.0114608. eCollection 2014.