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Gene Ontology (GO) Project http://www.geneontology.org/ Jane Lomax There is a lot of biological research output http://www.geneontology.org/ You’re interested in which genes control in mesoderm development… http://www.geneontology.org/ You get 6752 results! How will you ever find what you want? http://www.geneontology.org/ time Microarray data shows changed Defense response Immune response of Response toexpression stimulus Toll regulated genes thousands of genes. JAK-STAT regulated genes Puparial adhesion Molting cycle hemocyanin How will you spot the patterns? Amino acid catabolism Lipid metobolism Peptidase activity Protein catabloism Immune response Immune response Toll regulated genes attacked control Tree: pearson Coloredby: by: rson lw n3d ... lw n3d ... Colored ssification: Set_LW_n3d_5p_... Gene List: _LW_n3d_5p_... Gene List: Bregje Wertheim at the Centre for Evolutionary Genomics, Department of Biology, UCL and Eugene Schuster Group, EBI. Copy of Copy C5_RMA Copy ofofCopy of(Defa... C5_RMA (Defa... allall genes (14010)(14010) genes http://www.geneontology.org/ Scientists work hard http://www.geneontology.org/ There are lots of papers to read http://www.teamtechnology.co.uk/f-scientist.jpg More papers… http://www.teamtechnology.co.uk/f-scientist.jpg more and more and more… http://www.teamtechnology.co.uk/f-scientist.jpg more and more and more! Help! http://www.teamtechnology.co.uk/f-scientist.jpg The Gene Ontology provides a way to capture and represent biological all this knowledge in a computable form http://www.geneontology.org/ The Gene Ontology http://www.geneontology.org/ GO browser http://www.geneontology.org/ Search on ‘mesoderm development’ mesoderm development http://www.geneontology.org/ http://www.geneontology.org/ Definition of mesoderm development Gene products involved in mesoderm development http://www.geneontology.org/ • GO can be used to help analyse microarray data http://www.geneontology.org/ Microarray process: • • • • • • • • Treat samples Collect mRNA Label Hybridize Scan Normalize Select differentially regulated genes Understand the biological phenomena involved http://www.geneontology.org/ Traditional analysis • gene by gene basis • requires literature searching • time-consuming http://www.geneontology.org/ Traditional analysis Gene 1 Apoptosis Cell-cell signaling Protein phosphorylation Mitosis … Gene 3 Growth control Gene 4 Mitosis Nervous system Oncogenesis Pregnancy Protein phosphorylation Oncogenesis … Mitosis … Gene 2 Growth control Mitosis Oncogenesis Protein phosphorylation … Gene 100 Positive ctrl. of cell prolif Mitosis Oncogenesis Glucose transport … http://www.geneontology.org/ Using GO annotations • But by using GO annotations, this work has already been done GO:0006915 : apoptosis http://www.geneontology.org/ Grouping by process Apoptosis Gene 1 Gene 53 Positive ctrl. of cell prolif. Gene 7 Gene 3 Gene 12 … Mitosis Gene 2 Gene 5 Gene45 Gene 7 Gene 35 … Glucose transport Gene 7 Gene 3 Gene 6 … Growth Gene 5 Gene 2 Gene 6 … http://www.geneontology.org/ GO for microarray analysis • Annotations give ‘function’ label to genes • Ask meaningful questions of microarray data e.g. – genes involved in the same process, same/different expression patterns? http://www.geneontology.org/ How does the Gene Ontology work? http://www.geneontology.org/ GO structure • GO isn’t just a flat list of biological terms • terms are related within a hierarchy http://www.geneontology.org/ GO structure gene A http://www.geneontology.org/ GO structure • This means genes can be grouped according to userdefined levels • Allows broad overview of gene set or genome http://www.geneontology.org/ How does GO work? What information might we want to capture about a gene product? http://www.geneontology.org/ How does GO work? What information might we want to capture about a gene product? • What does the gene product do? http://www.geneontology.org/ How does GO work? What information might we want to capture about a gene product? • What does the gene product do? • Where and when does it act? http://www.geneontology.org/ How does GO work? What information might we want to capture about a gene product? • What does the gene product do? • Where and when does it act? • Why does it perform these activities? http://www.geneontology.org/ GO structure • GO terms divided into three parts: – cellular component – molecular function – biological process http://www.geneontology.org/ Cellular Component • where a gene product acts http://www.geneontology.org/ Cellular Component http://www.geneontology.org/ Cellular Component http://www.geneontology.org/ Cellular Component • Enzyme complexes in the component ontology refer to places, not activities. http://www.geneontology.org/ Molecular Function • activities or “jobs” of a gene product glucose-6-phosphate isomerase activity http://www.geneontology.org/ Molecular Function insulin binding insulin receptor activity http://www.geneontology.org/ Molecular Function drug transporter activity http://www.geneontology.org/ Molecular Function • A gene product may have several functions; a function term refers to a reaction or activity, not a gene product • Sets of functions make up a biological process http://www.geneontology.org/ Biological Process a commonly recognized series of events cell division http://www.geneontology.org/ Biological Process transcription http://www.geneontology.org/ Biological Process regulation of gluconeogenesis http://www.geneontology.org/ Biological Process limb development http://www.geneontology.org/ Biological Process courtship behavior http://www.geneontology.org/ Ontology Structure • Terms are linked by two relationships – is-a – part-of http://www.geneontology.org/ Ontology Structure cell membrane mitochondrial membrane is-a part-of chloroplast chloroplast membrane http://www.geneontology.org/ Ontology Structure • Ontologies are structured as a hierarchical directed acyclic graph (DAG) • Terms can have more than one parent and zero, one or more children http://www.geneontology.org/ Ontology Structure cell membrane mitochondrial membrane Directed Acyclic Graph (DAG) - multiple parentage allowed chloroplast chloroplast membrane http://www.geneontology.org/ Anatomy of a GO term id: GO:0006094 unique GO ID name: gluconeogenesis term name ontology namespace: process def: The formation of glucose from noncarbohydrate precursors, such as definition pyruvate, amino acids and glycerol. [http://cancerweb.ncl.ac.uk/omd/index.html] exact_synonym: glucose biosynthesis synonym xref_analog: MetaCyc:GLUCONEO-PWY database ref is_a: GO:0006006 parentage is_a: GO:0006092 http://www.geneontology.org/ GO can also be useful for resolving language conflicts amongst scientific communities http://www.geneontology.org/ In biology… Tactition Taction Tactile sense ? http://www.geneontology.org/ Tactition Taction Tactile sense perception of touch ; GO:0050975 http://www.geneontology.org/ Bud initiation? http://www.geneontology.org/ = tooth bud initiation = cellular bud initiation = flower bud initiation http://www.geneontology.org/ Categorization of gene products using GO is called annotation. So how does that happen? http://www.geneontology.org/ P05147 Take a gene or protein http://www.geneontology.org/ P05147 Find papers about it PMID: 2976880 http://www.geneontology.org/ P05147 PMID: 2976880 Find the GO term describing its function, process or location of action. GO:0047519 http://www.geneontology.org/ P05147 PMID: 2976880 What evidence do they show? IDA GO:0047519 http://www.geneontology.org/ P05147 PMID: 2976880 Record these: P05147 GO:0047519 IDA PMID:2976880 IDA GO:0047519 http://www.geneontology.org/ Submit to the GO Consortium http://www.geneontology.org/ Annotation appears in GO database http://www.geneontology.org/ Clark et al., 2005 Many species groups annotate We see the research of one function across all species http://www.geneontology.org/ Adding terms to the GO http://www.geneontology.org/ Developing GO • GO under constant development • International group of developers – central editorial office at EBI - 4 members • Developed in consultation with domain experts – Term suggestions handled through online tracking system http://www.geneontology.org/ http://www.geneontology.org/ http://www.geneontology.org/ http://www.geneontology.org/ http://www.geneontology.org/ 2006 Consortium Meeting, St. Croix, U.S. Virgin Islands, March 30 - April 3, 2006 http://www.geneontology.org/ Contributors dictyBase FlyBase GeneDB Gramene Reactome WormBase The GO Editorial Office Berkeley Bioinformatics and Ontology Project (BBOP) Gene Ontology Annotation @ EBI (GOA) Mouse Genome Database (MGD) and Gene Expression Database (GXD) Rat Genome Database (RGD) Saccharomyces Genome Database (SGD) The Arabidopsis Information Resource (TAIR) The Institute for Genomic Research (TIGR) Zebrafish Information Network (ZFIN) http://www.geneontology.org/