Identification of Conserved Moieties in Metabolic Networks by Graph Theoretical Analysis of Atom Transition Networks
Conserved moieties are groups of atoms that remain intact in all reactions of a metabolic network. Identification of conserved moieties gives insight into the structure and function of metabolic networks and facilitates metabolic modelling. All moiety conservation relations can be represented as nonnegative integer vectors in the left null space of the stoichiometric matrix corresponding to a biochemical network. Algorithms exist to compute such vectors based only on reaction stoichiometry but their computational complexity has limited their application to relatively small metabolic networks. Moreover, the vectors returned by existing algorithms do not, in general, represent conservation of a specific moiety with a defined atomic structure. Here, we show that identification of conserved moieties requires data on reaction atom mappings in addition to stoichiometry. We present a novel method to identify conserved moieties in metabolic networks by graph theoretical analysis of their underlying atom transition networks. Our method returns the exact group of atoms belonging to each conserved moiety as well as the corresponding vector in the left null space of the stoichiometric matrix. It can be implemented as a pipeline of polynomial time algorithms. Our implementation completes in under five minutes on a metabolic network with more than 4,000 massmore »
 Authors:

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 Univ. of Luxembourg, EschsurAlzette (Luxembourg). Luxembourg Centre for Systems Biomedicine
 Publication Date:
 Grant/Contract Number:
 SC0010429
 Type:
 Published Article
 Journal Name:
 PLoS Computational Biology (Online)
 Additional Journal Information:
 Journal Name: PLoS Computational Biology (Online); Journal Volume: 12; Journal Issue: 11; Journal ID: ISSN 15537358
 Publisher:
 Public Library of Science
 Research Org:
 Univ. of Luxembourg, EschsurAlzette (Luxembourg)
 Sponsoring Org:
 USDOE Office of Science (SC), Advanced Scientific Computing Research (ASCR) (SC21); USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC23); Luxembourg National Research Fund (FNR) (Luxembourg)
 Country of Publication:
 United States
 Language:
 English
 Subject:
 59 BASIC BIOLOGICAL SCIENCES; metabolic networks; metabolites; algorithms; carbon; graph theory; vector spaces; metabolic labeling; oxygen
 OSTI Identifier:
 1345286
 Alternate Identifier(s):
 OSTI ID: 1360088
Haraldsdóttir, Hulda S., and Fleming, Ronan M. T.. Identification of Conserved Moieties in Metabolic Networks by Graph Theoretical Analysis of Atom Transition Networks. United States: N. p.,
Web. doi:10.1371/journal.pcbi.1004999.
Haraldsdóttir, Hulda S., & Fleming, Ronan M. T.. Identification of Conserved Moieties in Metabolic Networks by Graph Theoretical Analysis of Atom Transition Networks. United States. doi:10.1371/journal.pcbi.1004999.
Haraldsdóttir, Hulda S., and Fleming, Ronan M. T.. 2016.
"Identification of Conserved Moieties in Metabolic Networks by Graph Theoretical Analysis of Atom Transition Networks". United States.
doi:10.1371/journal.pcbi.1004999.
@article{osti_1345286,
title = {Identification of Conserved Moieties in Metabolic Networks by Graph Theoretical Analysis of Atom Transition Networks},
author = {Haraldsdóttir, Hulda S. and Fleming, Ronan M. T.},
abstractNote = {Conserved moieties are groups of atoms that remain intact in all reactions of a metabolic network. Identification of conserved moieties gives insight into the structure and function of metabolic networks and facilitates metabolic modelling. All moiety conservation relations can be represented as nonnegative integer vectors in the left null space of the stoichiometric matrix corresponding to a biochemical network. Algorithms exist to compute such vectors based only on reaction stoichiometry but their computational complexity has limited their application to relatively small metabolic networks. Moreover, the vectors returned by existing algorithms do not, in general, represent conservation of a specific moiety with a defined atomic structure. Here, we show that identification of conserved moieties requires data on reaction atom mappings in addition to stoichiometry. We present a novel method to identify conserved moieties in metabolic networks by graph theoretical analysis of their underlying atom transition networks. Our method returns the exact group of atoms belonging to each conserved moiety as well as the corresponding vector in the left null space of the stoichiometric matrix. It can be implemented as a pipeline of polynomial time algorithms. Our implementation completes in under five minutes on a metabolic network with more than 4,000 mass balanced reactions. The scalability of the method enables extension of existing applications for moiety conservation relations to genomescale metabolic networks. Finally, we also give examples of new applications made possible by elucidating the atomic structure of conserved moieties.},
doi = {10.1371/journal.pcbi.1004999},
journal = {PLoS Computational Biology (Online)},
number = 11,
volume = 12,
place = {United States},
year = {2016},
month = {11}
}