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PMID: 17463022 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A network-based method for target selection in metabolic networks.

Bioinformatics (Oxford, England) ·Vol. 23 ·No. 13 ·2007-07-01 ·Pages 1616-22

Guimerà R, Sales-Pardo M, Amaral LA

Abstract

The lack of new antimicrobials, combined with increasing microbial resistance to old ones, poses a serious threat to public health. With hundreds of genomes sequenced, systems biology promises to help in solving this problem by uncovering new drug targets. Here, we propose an approach that is based on the mapping of the interactions between biochemical agents, such as proteins and metabolites, onto complex networks. We report that nodes and links in complex biochemical networks can be grouped into a small number of classes, based on their role in connecting different functional modules. Specifically, for metabolic networks, in which nodes represent metabolites and links represent enzymes, we demonstrate that some enzyme classes are more likely to be essential, some are more likely to be species-specific and some are likely to be both essential and specific. Our network-based enzyme classification scheme is thus a promising tool for the identification of drug targets. Supplementary data are available at Bioinformatics online.

MeSH Terms
Algorithms Bacteria/metabolism Bacterial Proteins/metabolism Drug Delivery Systems/methods Drug Design Models, Biological Signal Transduction/physiology
Chemicals
Bacterial Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Guimerà R
Northwestern Institute on Complex Systems and Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA. [email protected]
Sales-Pardo M
Amaral L A N
References (38)
38 references, click to expand
  1. From genomics to chemical genomics: new developments in KEGG.
    Nucleic Acids Res. 2006 Jan 1;34(Database issue):D354-7 PMID: 16381885
  2. LIGAND: chemical database for enzyme reactions.
    Bioinformatics. 1998;14(7):591-9 PMID: 9730924
  3. KEGG: kyoto encyclopedia of genes and genomes.
    Nucleic Acids Res. 2000 Jan 1;28(1):27-30 PMID: 10592173
  4. Trends in antimicrobial drug development: implications for the future.
    Clin Infect Dis. 2004 May 1;38(9):1279-86 PMID: 15127341
  5. Observing local and global properties of metabolic pathways: 'load points' and 'choke points' in the metabolic networks.
    Bioinformatics. 2006 Jul 15;22(14):1767-74 PMID: 16682421
  6. Robustness analysis of the Escherichia coli metabolic network.
    Biotechnol Prog. 2000 Nov-Dec;16(6):927-39 PMID: 11101318
  7. Comment on "Subgraphs in random networks".
    Phys Rev E Stat Nonlin Soft Matter Phys. 2004 Nov;70(5 Pt 2):058101; author reply 058102 PMID: 15600808
  8. Clustered organization of cortical connectivity.
    Neuroinformatics. 2004;2(3):353-60 PMID: 15365196
  9. An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM/GPR).
    Genome Biol. 2003;4(9):R54 PMID: 12952533
  10. Hierarchical organization of modularity in metabolic networks.
    Science. 2002 Aug 30;297(5586):1551-5 PMID: 12202830
  11. Evidence for dynamically organized modularity in the yeast protein-protein interaction network.
    Nature. 2004 Jul 1;430(6995):88-93 PMID: 15190252
  12. Functional essentiality from topology features in metabolic networks: a case study in yeast.
    FEBS Lett. 2005 Aug 29;579(21):4642-6 PMID: 16095595
  13. Specificity and stability in topology of protein networks.
    Science. 2002 May 3;296(5569):910-3 PMID: 11988575
  14. TTD: Therapeutic Target Database.
    Nucleic Acids Res. 2002 Jan 1;30(1):412-5 PMID: 11752352
  15. Scale-rich metabolic networks.
    Phys Rev Lett. 2005 Apr 29;94(16):168101 PMID: 15904266
  16. Reconstruction of metabolic networks from genome data and analysis of their global structure for various organisms.
    Bioinformatics. 2003 Jan 22;19(2):270-7 PMID: 12538249
  17. Distributed robustness versus redundancy as causes of mutational robustness.
    Bioessays. 2005 Feb;27(2):176-88 PMID: 15666345
  18. Minimal cut sets in biochemical reaction networks.
    Bioinformatics. 2004 Jan 22;20(2):226-34 PMID: 14734314
  19. Functional cartography of complex metabolic networks.
    Nature. 2005 Feb 24;433(7028):895-900 PMID: 15729348
  20. Lethality and centrality in protein networks.
    Nature. 2001 May 3;411(6833):41-2 PMID: 11333967
  21. Community structure in social and biological networks.
    Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):7821-6 PMID: 12060727
  22. Experimental determination and system level analysis of essential genes in Escherichia coli MG1655.
    J Bacteriol. 2003 Oct;185(19):5673-84 PMID: 13129938
  23. Finding and evaluating community structure in networks.
    Phys Rev E Stat Nonlin Soft Matter Phys. 2004 Feb;69(2 Pt 2):026113 PMID: 14995526
  24. Biological networks and analysis of experimental data in drug discovery.
    Drug Discov Today. 2005 May 1;10(9):653-62 PMID: 15894230
  25. Cartography of complex networks: modules and universal roles.
    J Stat Mech. 2005 Feb 1;2005(P02001):nihpa35573 PMID: 18159217
  26. The millennium bugs--the need for and development of new antibacterials.
    Int J Antimicrob Agents. 2000 Sep;16(1):51-9 PMID: 11185414
  27. Classes of complex networks defined by role-to-role connectivity profiles.
    Nat Phys. 2007;3(1):63-69 PMID: 18618010
  28. Subnetwork hierarchies of biochemical pathways.
    Bioinformatics. 2003 Mar 1;19(4):532-8 PMID: 12611809
  29. Metabolic network analysis of the causes and evolution of enzyme dispensability in yeast.
    Nature. 2004 Jun 10;429(6992):661-4 PMID: 15190353
  30. Expanded metabolic reconstruction of Helicobacter pylori (iIT341 GSM/GPR): an in silico genome-scale characterization of single- and double-deletion mutants.
    J Bacteriol. 2005 Aug;187(16):5818-30 PMID: 16077130
  31. Connectivity and complexity: the relationship between neuroanatomy and brain dynamics.
    Neural Netw. 2000 Oct-Nov;13(8-9):909-22 PMID: 11156201
  32. The small world inside large metabolic networks.
    Proc Biol Sci. 2001 Sep 7;268(1478):1803-10 PMID: 11522199
  33. The large-scale organization of metabolic networks.
    Nature. 2000 Oct 5;407(6804):651-4 PMID: 11034217
  34. From molecular to modular cell biology.
    Nature. 1999 Dec 2;402(6761 Suppl):C47-52 PMID: 10591225
  35. The Escherichia coli MG1655 in silico metabolic genotype: its definition, characteristics, and capabilities.
    Proc Natl Acad Sci U S A. 2000 May 9;97(10):5528-33 PMID: 10805808
  36. Lack of development of new antimicrobial drugs: a potential serious threat to public health.
    Lancet Infect Dis. 2005 Feb;5(2):115-9 PMID: 15680781
  37. Modularity from fluctuations in random graphs and complex networks.
    Phys Rev E Stat Nonlin Soft Matter Phys. 2004 Aug;70(2 Pt 2):025101 PMID: 15447530
  38. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
    Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 PMID: 9254694
Article Info
Journal
Bioinformatics (Oxford, England)
Abbr.
Bioinformatics
ISSN
1367-4811
Published
2007-07-01
Epub
2007-00-26
Pages
1616-22
Language
English
Region
England
NLM ID
9808944
PMCID
PMC2149892
Subset
IM
Grants
NIGMS NIH HHS · K25 GM069546-04 · United States
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