The Genom of Homo sapiens.pdf

234 ASHBURNER ET AL.cabulary for the description of mutations at both sequenceand grosser levels in the context of genomic databases.The four major nodes of the complete Sequence Ontologyallow for the annotation of chromosome mutations, theconsequences of mutation, objects that can be located (inbase coordinates) on a sequence, and general attributes ofgenes.CONCLUSIONThe GO is not a mere exercise in knowledge representation;rather, its development is driven by a purely practicalneed—the need to provide semantic standards sothat biological data can be more usefully stored andqueried. The task is nontrivial. It is to create a languagefor biological research that is both computationallytractable and humanly understandable.The technical aspect of the development of GO and relatedontologies is, however, relatively trivial comparedto the social aspect of the problem. It is predicated oncommunity agreement. The community of developersand researchers must agree to agree. Achieving resolutionrequires a great deal of patience, as reaching a commonunderstanding is often a lengthy process. It is this acceptance,that reaching community consensus is essential,that is the most notable aspect of the GO Consortium. Butthis is not itself sufficient; building ontologies is not anend in itself, the ontologies must be implemented, whichrequires their acceptance by the broader community ofbioinformaticists and biologists. A common computablebiological language is essential in order to communicate,share, and exploit information from the past and present.Without a strong semantic foundation, we will be livingin a tower of Babel. With a common language, the communityis connected and will benefit both individuallyfrom the ready availability of information and collectivelyby sharing and coordinating the exchange of information.Although the challenge is formidable, the benefitsare even greater.ACKNOWLEDGMENTSThe Gene Ontology Consortium is supported by a grantfrom the National Institutes of Health (HG-02273, PIJudy Blake), and a grant from the Medical ResearchCouncil, UK to M.A. (G-9827766). The early developmentof GO was supported by donations from AstraZeneca and Incyte Genomics. C.J.M. is supported by theHoward Hughes Medical Institute. We thank our manycolleagues in the GO Consortium, without whom thisproject would have been impossible. We also thank themany users of GO for their feedback. Our use of descriptionlogic formats has benefited greatly from discussionswith Drs. Robert Stevens and Chris Wroe of the Universityof Manchester.REFERENCESAdams M.D., Celniker S.E., Holt R.A., Evans C.A., GocayneJ.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A.,Galle R.F., George R.A., Lewis S.E., Richards S., AshburnerM., Henderson S.N., Sutton G.G., Wortman J.R., YandellM.D., Zhang Q., Chen L.X., Brandon R.C., Rogers Y.H.,Blazej R.G., Champe M., and Pfeiffer B.D., et al. 2000. Thegenome sequence of Drosophila melanogaster. Science 287:2185.Baader F., McGuinness D., Nardi D., and Patel-Schneider P.,Eds. 2003. The Description logic handbook. Cambridge UniversityPress, Cambridge, United Kingdom.Bard J. and Winter R. 2001. Ontologies of developmentalanatomy: Their current and future roles. Brief. Bioinform. 2:289.Barrell B.G. and Clark B.F.C. 1974. Handbook of nucleic acidsequences. Joynson-Bruvvers, Eynsham, United Kingdom.Bennett J.M. and Kendrew J.C. 1952. Computation of Fouriersyntheses with a digital electronic calculating machine. ActaCrystallogr. 5: 109.Berriz G.F., White J.V., King O.D., and Roth, F.P. 2003. GoFishfinds genes with combinations of Gene Ontology attributes.Bioinformatics 19: 788.Brachman R.J. 1983. What ISA-A is and isn’t: An analysis oflinks in semantic networks. Computer 16: 30.Croft L.R. 1973. Handbook of protein sequences. Joynson-Bruvvers, Eynsham, United Kingdom.Davidson S.B., Overton C., and Buneman P. 1995. Challenges inintegrating biological data sources. J. Comput. Biol. 2: 557.Dayhoff M.O., Eck R.V., Chang Y., and Sochard S.R. 1965. Atlasof protein sequence and structure. National BiomedicalResearch Foundation, Washington, D.C.Draghici S., Khatri P., Martins R.P., Ostermeier G.C., andKrawetz S.A. 2003. Global profiling of gene expression. Genomics81: 98.Durbin R. and Thierry-Mieg J. 1991-. A C. elegans database.(http://www.faqs.org/faqs/acedb-faq/).Fasman K. 1994. Restructuring the genome data base: A modelfor a federation of biological databases. J. Comput. Biol. 1:165.Fellbaum C., Ed. 1998. WordNet. An electronic lexicaldatabase. MIT Press, Cambridge, Massachusetts.Gilks W.R., Audit B., De Angelis D., Tsoka S., and OuzounisC.A. 2002. Modeling the percolation of annotation errors in adatabase of protein sequences. Bioinformatics 18: 1641.GK (Genome KnowledgeBase). 2003. (http://www.genomeknowledge.org)Hebert P.D.N., Cywinska A., Ball S.L., and deWaard J.R. 2003.Biological identification through DNA barcodes. Proc. Roy.Soc. Lond. B 270: 312.Hill D.P., Blake J.A., Richardson J.E., and Ringwald M. 2002.Extension and integration of the gene ontology (GO): CombiningGO vocabularies with external vocabularies. GenomeRes. 12: 1982.Hirschman L., Park J.C., Tsujii, J., Wong L., and Wu C.H. 2002.Accomplishments and challenges in literature data mining forbiology. Bioinformatics 18: 1553.Huxley H.E. 1990. An early adventure in crystallographic computing.In Selections and reflections: The legacy of Sir L.Bragg (ed. J.M. Thomas and D. Phillips), p.133. Science Reviews,Northwood, United Kingdom.Hvidsten T.R., Komorowski J., Sandvik A.K., and Laegreid A.2001. Predicting gene function from gene expressions and ontologies.Pac. Symp. Biocomput. 2001: 299.Jensen L.J., Gupta R., Staerfeldt H.H., and Brunak S. 2003. Predictionof human protein function according to Gene Ontologycategories. Bioinformatics 19: 635.Jenssen T.K., Laegreid A., Komorowski J., and Hovig E. 2001.A literature network of human genes for high-throughputanalysis of gene expression. Nat. Genet. 28: 21.Kay L.E. 2000. Who wrote the book of life? A history of the geneticcode. Stanford University Press, Stanford, California.Khatri P., Draghici S., Ostermeier G.C., and Krawetz S.A. 2002.Profiling gene expression using onto-express. Genomics 79:266.King O.D., Foulger R.E., Dwight S.S., White J.V., and Roth F.P.