The outcomes of pathway database computations depend on pathway ontology
Abstract
Different biological notions of pathways are used in different pathway databases. Those pathway ontologies significantly impact pathway computations. Computational users of pathway databases will obtain different results depending on the pathway ontology used by the databases they employ, and different pathway ontologies are preferable for different end uses. We explore differences in pathway ontologies by comparing the BioCyc and KEGG ontologies. The BioCyc ontology defines a pathway as a conserved, atomic module of the metabolic network of a single organism, i.e. often regulated as a unit, whose boundaries are defined at highconnectivity stable metabolites. KEGG pathways are on average 4.2 times larger than BioCyc pathways, and combine multiple biological processes from different organisms to produce a substrate-centered reaction mosaic. We compared KEGG and BioCyc pathways using genome context methods, which determine the functional relatedness of pairs of genes. For each method we employed, a pair of genes randomly selected from a BioCyc pathway is more likely to be related by that method than is a pair of genes randomly selected from a KEGG pathway, supporting the conclusion that the BioCyc pathway conceptualization is closer to a single conserved biological process than is that of KEGG.
- Authors:
-
- SRI International, Menlo Park, CA (United States). Artificial Intelligence Center. Bioinformatics Research Group
- Publication Date:
- Research Org.:
- Stanford Univ., CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division; National Institutes of Health (NIH)
- OSTI Identifier:
- 1625405
- Grant/Contract Number:
- FG03-01ER63219; RR07861; GM70065
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nucleic Acids Research
- Additional Journal Information:
- Journal Volume: 34; Journal Issue: 13; Journal ID: ISSN 0305-1048
- Publisher:
- Oxford University Press
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Biochemistry & Molecular Biology
Citation Formats
Green, M. L., and Karp, P. D. The outcomes of pathway database computations depend on pathway ontology. United States: N. p., 2006.
Web. doi:10.1093/nar/gkl438.
Green, M. L., & Karp, P. D. The outcomes of pathway database computations depend on pathway ontology. United States. https://doi.org/10.1093/nar/gkl438
Green, M. L., and Karp, P. D. Fri .
"The outcomes of pathway database computations depend on pathway ontology". United States. https://doi.org/10.1093/nar/gkl438. https://www.osti.gov/servlets/purl/1625405.
@article{osti_1625405,
title = {The outcomes of pathway database computations depend on pathway ontology},
author = {Green, M. L. and Karp, P. D.},
abstractNote = {Different biological notions of pathways are used in different pathway databases. Those pathway ontologies significantly impact pathway computations. Computational users of pathway databases will obtain different results depending on the pathway ontology used by the databases they employ, and different pathway ontologies are preferable for different end uses. We explore differences in pathway ontologies by comparing the BioCyc and KEGG ontologies. The BioCyc ontology defines a pathway as a conserved, atomic module of the metabolic network of a single organism, i.e. often regulated as a unit, whose boundaries are defined at highconnectivity stable metabolites. KEGG pathways are on average 4.2 times larger than BioCyc pathways, and combine multiple biological processes from different organisms to produce a substrate-centered reaction mosaic. We compared KEGG and BioCyc pathways using genome context methods, which determine the functional relatedness of pairs of genes. For each method we employed, a pair of genes randomly selected from a BioCyc pathway is more likely to be related by that method than is a pair of genes randomly selected from a KEGG pathway, supporting the conclusion that the BioCyc pathway conceptualization is closer to a single conserved biological process than is that of KEGG.},
doi = {10.1093/nar/gkl438},
journal = {Nucleic Acids Research},
number = 13,
volume = 34,
place = {United States},
year = {Fri Jul 28 00:00:00 EDT 2006},
month = {Fri Jul 28 00:00:00 EDT 2006}
}
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Works referenced in this record:
Prediction of protein function and pathways in the genome era
journal, April 2004
- Gabald�n, T.; Huynen, M. A.
- Cellular and Molecular Life Sciences (CMLS), Vol. 61, Issue 7-8
Comparison of network-based pathway analysis methods
journal, August 2004
- Papin, Jason A.; Stelling, Joerg; Price, Nathan D.
- Trends in Biotechnology, Vol. 22, Issue 8
Integrated pathway–genome databases and their role in drug discovery
journal, July 1999
- Karp, Peter D.; Krummenacker, Markus; Paley, Suzanne
- Trends in Biotechnology, Vol. 17, Issue 7
Conservation of gene order: a fingerprint of proteins that physically interact
journal, September 1998
- Dandekar, T.
- Trends in Biochemical Sciences, Vol. 23, Issue 9
PAX of mind for pathway researchers
journal, July 2005
- Luciano, Joanne S.
- Drug Discovery Today, Vol. 10, Issue 13
Prediction of protein interactions: metabolic enzymes are frequently involved in gene fusion
journal, October 2000
- Tsoka, Sophia; Ouzounis, Christos A.
- Nature Genetics, Vol. 26, Issue 2
GenMAPP, a new tool for viewing and analyzing microarray data on biological pathways
journal, May 2002
- Dahlquist, Kam D.; Salomonis, Nathan; Vranizan, Karen
- Nature Genetics, Vol. 31, Issue 1
Systems biology markup language: Level 2 and beyond
journal, December 2003
- Finney, A.; Hucka, M.
- Biochemical Society Transactions, Vol. 31, Issue 6
Genome evolution reveals biochemical networks and functional modules
journal, December 2003
- von Mering, C.; Zdobnov, E. M.; Tsoka, S.
- Proceedings of the National Academy of Sciences, Vol. 100, Issue 26
The use of gene clusters to infer functional coupling
journal, March 1999
- Overbeek, R.; Fonstein, M.; D'Souza, M.
- Proceedings of the National Academy of Sciences, Vol. 96, Issue 6
Assigning protein functions by comparative genome analysis: Protein phylogenetic profiles
journal, April 1999
- Pellegrini, M.; Marcotte, E. M.; Thompson, M. J.
- Proceedings of the National Academy of Sciences, Vol. 96, Issue 8
Microbial Genescapes: Phyletic and Functional Patterns of ORF Distribution among Prokaryotes
journal, January 1998
- Gaasterland, Terry; Ragan, Mark A.
- Microbial & Comparative Genomics, Vol. 3, Issue 4
The Pathway Tools software
journal, July 2002
- Karp, P. D.; Paley, S.; Romero, P.
- Bioinformatics, Vol. 18, Issue Suppl 1
Identification of functional links between genes using phylogenetic profiles
journal, August 2003
- Wu, J.; Kasif, S.; DeLisi, C.
- Bioinformatics, Vol. 19, Issue 12
Representations of molecular pathways: an evaluation of SBML, PSI MI and BioPAX
journal, October 2005
- Strömbäck, Lena; Lambrix, Patrick
- Bioinformatics, Vol. 21, Issue 24
The KEGG resource for deciphering the genome
journal, January 2004
- Kanehisa, M.
- Nucleic Acids Research, Vol. 32, Issue 90001
STRING: known and predicted protein-protein associations, integrated and transferred across organisms
journal, December 2004
- von Mering, C.
- Nucleic Acids Research, Vol. 33, Issue Database issue
Expansion of the BioCyc collection of pathway/genome databases to 160 genomes
journal, October 2005
- Karp, P. D.
- Nucleic Acids Research, Vol. 33, Issue 19
Detecting Protein Function and Protein-Protein Interactions from Genome Sequences
journal, July 1999
- Marcotte, E. M.
- Science, Vol. 285, Issue 5428
BioWarehouse: a bioinformatics database warehouse toolkit
journal, March 2006
- Lee, Thomas J.; Pouliot, Yannick; Wagner, Valerie
- BMC Bioinformatics, Vol. 7, Issue 1
Identifying Protein Function—A Call for Community Action
journal, March 2004
- Roberts, Richard J.
- PLoS Biology, Vol. 2, Issue 3
Works referencing / citing this record:
Large-scale reconstruction and phylogenetic analysis of metabolic environments
journal, September 2008
- Borenstein, E.; Kupiec, M.; Feldman, M. W.
- Proceedings of the National Academy of Sciences, Vol. 105, Issue 38
UniPathway: a resource for the exploration and annotation of metabolic pathways
journal, November 2011
- Morgat, Anne; Coissac, Eric; Coudert, Elisabeth
- Nucleic Acids Research, Vol. 40, Issue D1
Pathway Analysis: State of the Art
journal, December 2015
- García-Campos, Miguel A.; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique
- Frontiers in Physiology, Vol. 6
An updated metabolic view of the Bacillus subtilis 168 genome
journal, April 2013
- Belda, Eugeni; Sekowska, Agnieszka; Le Fèvre, François
- Microbiology, Vol. 159, Issue Pt_4
Influence of pathway topology and functional class on the molecular evolution of human metabolic genes
posted_content, January 2018
- Montanucci, Ludovica; Laayouni, Hafid; Dobón, Begoña
- PLOS One
Influence of pathway topology and functional class on the molecular evolution of human metabolic genes
journal, December 2018
- Montanucci, Ludovica; Laayouni, Hafid; Dobon, Begoña
- PLOS ONE, Vol. 13, Issue 12
Pathway Tools version 13.0: integrated software for pathway/genome informatics and systems biology
journal, December 2009
- Karp, P. D.; Paley, S. M.; Krummenacker, M.
- Briefings in Bioinformatics, Vol. 11, Issue 1
Comparison of human cell signaling pathway databases—evolution, drawbacks and challenges
journal, January 2015
- Chowdhury, Saikat; Sarkar, Ram Rup
- Database, Vol. 2015
Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease
journal, December 2011
- Greenblum, S.; Turnbaugh, P. J.; Borenstein, E.
- Proceedings of the National Academy of Sciences, Vol. 109, Issue 2
SolCyc: a database hub at the Sol Genomics Network (SGN) for the manual curation of metabolic networks in Solanum and Nicotiana specific databases
journal, January 2018
- Foerster, Hartmut; Bombarely, Aureliano; Battey, James N. D.
- Database, Vol. 2018
The MetaCyc Database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases
journal, December 2007
- Caspi, R.; Foerster, H.; Fulcher, C. A.
- Nucleic Acids Research, Vol. 36, Issue Database
A systematic comparison of the MetaCyc and KEGG pathway databases
journal, January 2013
- Altman, Tomer; Travers, Michael; Kothari, Anamika
- BMC Bioinformatics, Vol. 14, Issue 1
Genetics and epigenetics of rheumatoid arthritis
journal, February 2013
- Viatte, Sebastien; Plant, Darren; Raychaudhuri, Soumya
- Nature Reviews Rheumatology, Vol. 9, Issue 3
Ten Years of Pathway Analysis: Current Approaches and Outstanding Challenges
journal, February 2012
- Khatri, Purvesh; Sirota, Marina; Butte, Atul J.
- PLoS Computational Biology, Vol. 8, Issue 2
Consistency, comprehensiveness, and compatibility of pathway databases
journal, September 2010
- Soh, Donny; Dong, Difeng; Guo, Yike
- BMC Bioinformatics, Vol. 11, Issue 1
A survey of metabolic databases emphasizing the MetaCyc family
journal, April 2011
- Karp, Peter D.; Caspi, Ron
- Archives of Toxicology, Vol. 85, Issue 9
Advancing Science through Mining Libraries, Ontologies, and Communities
journal, July 2011
- Evans, James A.; Rzhetsky, Andrey
- Journal of Biological Chemistry, Vol. 286, Issue 27
Comparison of human cell signaling pathway databases—evolution, drawbacks and challenges
journal, January 2015
- Chowdhury, Saikat; Sarkar, Ram Rup
- Database, Vol. 2015
SolCyc: a database hub at the Sol Genomics Network (SGN) for the manual curation of metabolic networks in Solanum and Nicotiana specific databases
journal, January 2018
- Foerster, Hartmut; Bombarely, Aureliano; Battey, James N. D.
- Database, Vol. 2018
The MetaCyc Database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases
journal, December 2007
- Caspi, R.; Foerster, H.; Fulcher, C. A.
- Nucleic Acids Research, Vol. 36, Issue Database
Pathway Analysis Integrating Genome-Wide and Functional Data Identifies PLCG2 as a Candidate Gene for Age-Related Macular Degeneration
journal, September 2019
- Waksmunski, Andrea R.; Grunin, Michelle; Kinzy, Tyler G.
- Investigative Opthalmology & Visual Science, Vol. 60, Issue 12
Consistency, comprehensiveness, and compatibility of pathway databases
journal, September 2010
- Soh, Donny; Dong, Difeng; Guo, Yike
- BMC Bioinformatics, Vol. 11, Issue 1
Finding consistent disease subnetworks across microarray datasets
journal, November 2011
- Soh, Donny; Dong, Difeng; Guo, Yike
- BMC Bioinformatics, Vol. 12, Issue S13
Effects of protein interaction data integration, representation and reliability on the use of network properties for drug target prediction
journal, November 2012
- Mora, Antonio; Donaldson, Ian M.
- BMC Bioinformatics, Vol. 13, Issue 1
A systematic comparison of the MetaCyc and KEGG pathway databases
journal, January 2013
- Altman, Tomer; Travers, Michael; Kothari, Anamika
- BMC Bioinformatics, Vol. 14, Issue 1
Discovering functional linkages and uncharacterized cellular pathways using phylogenetic profile comparisons: a comprehensive assessment
journal, May 2007
- Jothi, Raja; Przytycka, Teresa M.; Aravind, L.
- BMC Bioinformatics, Vol. 8, Issue 1
Metabolic innovations towards the human lineage
journal, January 2008
- Freilich, Shiri; Goldovsky, Leon; Ouzounis, Christos A.
- BMC Evolutionary Biology, Vol. 8, Issue 1
Integration of metabolic databases for the reconstruction of genome-scale metabolic networks
journal, January 2010
- Radrich, Karin; Tsuruoka, Yoshimasa; Dobson, Paul
- BMC Systems Biology, Vol. 4, Issue 1
Critical assessment of human metabolic pathway databases: a stepping stone for future integration
journal, October 2011
- Stobbe, Miranda D.; Houten, Sander M.; Jansen, Gerbert A.
- BMC Systems Biology, Vol. 5, Issue 1
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes
journal, January 2009
- Kastenmüller, Gabi; Schenk, Maria; Gasteiger, Johann
- Genome Biology, Vol. 10, Issue 3
The conservation and evolutionary modularity of metabolism
journal, January 2009
- Peregrín-Alvarez, José M.; Sanford, Chris; Parkinson, John
- Genome Biology, Vol. 10, Issue 6
Ten Years of Pathway Analysis: Current Approaches and Outstanding Challenges
journal, February 2012
- Khatri, Purvesh; Sirota, Marina; Butte, Atul J.
- PLoS Computational Biology, Vol. 8, Issue 2
The CanOE Strategy: Integrating Genomic and Metabolic Contexts across Multiple Prokaryote Genomes to Find Candidate Genes for Orphan Enzymes
journal, May 2012
- Smith, Adam Alexander Thil; Belda, Eugeni; Viari, Alain
- PLoS Computational Biology, Vol. 8, Issue 5
Deficiency in Nucleotide Excision Repair Family Gene Activity, Especially ERCC3, Is Associated with Non-Pigmented Hair Fiber Growth
journal, May 2012
- Yu, Mei; Bell, Robert H.; Ho, Maggie M.
- PLoS ONE, Vol. 7, Issue 5
Generation and Analysis of a Mouse Intestinal Metatranscriptome through Illumina Based RNA-Sequencing
journal, April 2012
- Xiong, Xuejian; Frank, Daniel N.; Robertson, Charles E.
- PLoS ONE, Vol. 7, Issue 4
Pathway Analysis: State of the Art
journal, December 2015
- García-Campos, Miguel A.; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique
- Frontiers in Physiology, Vol. 6
A novel approach to select differential pathways associated with hypertrophic cardiomyopathy based on gene co-expression analysis
journal, January 2017
- Chen, Xiao-Min; Feng, Ming-Jun; Shen, Cai-Jie
- Molecular Medicine Reports, Vol. 16, Issue 1