Document Type
Article
Original Publication Date
2012
Journal/Book/Conference Title
Advances in Bioinformatics
Volume
2012
Issue
Article ID 323472, 10 pages
DOI
10.1155/2012/323472
Date of Submission
July 2014
Abstract
Constraint-based metabolic models are currently the most comprehensive system-wide models of cellular metabolism. Several challenges arise when building an in silico constraint-based model of an organism that need to be addressed before flux balance analysis (FBA) can be applied for simulations. An algorithm called FBA-Gap is presented here that aids the construction of a working model based on plausible modifications to a given list of reactions that are known to occur in the organism. When applied to a working model, the algorithm gives a hypothesis concerning a minimal medium for sustaining the cell in culture. The utility of the algorithm is demonstrated in creating a new model organism and is applied to four existing working models for generating hypotheses about culture media. In modifying a partial metabolic reconstruction so that biomass may be produced using FBA, the proposed method is more efficient than a previously proposed method in that fewer new reactions are added to complete the model. The proposed method is also more accurate than other approaches in that only biologically plausible reactions and exchange reactions are used.
Rights
Copyright © 2012 J. Paul Brooks et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Is Part Of
VCU Statistical Sciences and Operations Research Faculty Publications
Comments
Also available open access online through Hindawi at http://dx.doi.org/10.1155/2012/323472
The Supplementary Material contains a proof that FBA-Gap is NP-Complete and tables related to computational results. A list of low-cost exchange reactions is in Table S1. Results from the first round of FBA-Gap for B. subtilis, T. cruzi, H. pylori, E. coli, and C. neoformans are in Table S2. For the C. neoformans model, the _rst step of FBA-Gap yields that the metabolites in Table S3 are an in_nite distance from the biomass reaction. The results of three rounds of gap analysis are in Tables S4-S7 below. Each table contains the transport reactions selected, and the action taken to avoid high-cost transports in the next round of gap analysis. In general, reactions are added only if they are in the MetModel GUI database and if KEGG specifies that a gene encodes the appropriate enzyme in the organism. The reactions in the final working model for C. neoformans is in Table S8. Table S9 contains reactions deleted from the B. subtilis model, and Table S10 contains the results of applying FBA-Gap to the broken model.