Part II GO-Vocabulary of Genome
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Transcript of Part II GO-Vocabulary of Genome
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Part II GO-Vocabulary of Genome
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S. cerevisiae
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D. melanogaster
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Cells that normally surviveCED-9
ON
CED-3CED-4OFF
CED-9OFF
CED-3CED-4
ON
Cells that normally die
C elegans
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M. musculus
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MCM3
MCM2
CDC46/MCM5
CDC47/MCM7
CDC54/MCM4
MCM6
These proteins form a hexamer in the species that have been examined
Comparison of sequences from 4 organisms
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A Common Language for Annotation of Genes from
Yeast, Flies and Mice
The Gene Ontologies
…and Plants and Worms
…and Humans
…and anything else!
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Gene Ontology - 1998
FlyBase Drosophila Cambridge, EBI, HarvardBerkeley & Bloomington.
SGD Saccharomyces Stanford.
MGI Mus Jackson Labs., Bar Harbor.
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Gene Ontology -now
• Fruitfly - FlyBase• Budding yeast - Saccharomyces Genome Database (SGD)• Mouse - Mouse Genome Database (MGD & GXD)• Rat - Rat Genome Database (RGD)• Weed - The Arabidopsis Information Resource (TAIR)• Worm - WormBase• Dictyostelium discoidem - Dictybase• InterPro/UniProt at EBI - InterPro• Fission yeast - Pombase• Human - UniProt, Ensembl, NCBI, Incyte, Celera, Compugen• Parasites - Plasmodium, Trypanosoma, Leishmania - GeneDB - Sa
nger• Microbes - Vibrio, Shewanella, B. anthracus, … - TIGR• Grasses - rice & maize - Gramene database• zebra fish – Zfin.........
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To provide
structured controlled vocabularies
for the
representation of biological knowledge
in
biological databases.
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• Be open source
• Use open standards
• Make data & code available without constraint
• Involve your community
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Outline
• Introduction to the Gene Ontologies (GO)
• Annotations to GO terms
• GO Tools
• Applications of GO
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Gene Ontology Objectives• GO represents concepts used to classify
specific parts of our biological knowledge:– Biological Process– Molecular Function– Cellular Component
• GO develops a common language applicable to any organism
• GO terms can be used to annotate gene products from any species, allowing comparison of information across species
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GO: Three ontologies
Where does it act?
What processes is it involved in?
What does it do? Molecular Function
Cellular Component
Biological Process
gene product
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Function (what) Process (why)
Drive nail (into wood) Carpentry
Drive stake (into soil) Gardening
Smash roach Pest Control
Clown’s juggling object Entertainment
Example: Gene Product = hammer
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Biological ExamplesMolecular FunctionMolecular FunctionBiological ProcessBiological Process Cellular ComponentCellular Component
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• Molecular Function = elemental activity/task– the tasks performed by individual gene products; examples are carbohydrate b
inding and ATPase activity
• Biological Process = biological goal or objective
– broad biological goals, such as mitosis or purine metabolism, that are accomplished by ordered assemblies of molecular functions
• Cellular Component = location or complex– subcellular structures, locations, and macromolecular complexes; examples in
clude nucleus, telomere, and RNA polymerase II holoenzyme
The 3 Gene Ontologies
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Molecular Function
• A single reaction or activity, not a gene product
• A gene product may have several functions
• Sets of functions make up a biological process
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Molecular Function
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Carbonate dehydratase activity
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Biological Process
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Gluconeogenesis
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Cellular Component
• where a gene product acts
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Mitochondrial membrane
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term: gluconeogenesis
id: GO:0006094
definition: The formation of glucose from noncarbohydrate precursors, such as pyruvate, amino acids and glycerol.
What’s in a GO term?
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What’s in a name?
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Molecular Function 7,309 terms Biological Process 10,041 terms Cellular Component 1,629 terms
Total 18, 975 terms
Definitions: 94.9 %Obsolete terms: 992
Content of GO
As of October 2005
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What’s in a name?
• Glucose synthesis• Glucose biosynthesis• Glucose formation• Glucose anabolism• Gluconeogenesis
• All refer to the process of making glucose from simpler components
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tree directed acyclic graph
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Nucleus
Nucleoplasm Nuclearenvelope
ChromosomePerinuclear spaceNucleolus
A child is a subset ofa parent’s elements
The cell component term Nucleus has 5 children
Parent-Child Relationships
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Ontology RelationshipsDirected Acyclic Graph
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Evidence Codes for GO Evidence Codes for GO AnnotationsAnnotations
http://www.geneontology.org/doc/GO.evidence.html
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IEA Inferred from Electronic Annotation
ISS Inferred from Sequence Similarity
IEP Inferred from Expression Pattern
IMP Inferred from Mutant Phenotype
IGI Inferred from Genetic Interaction
IPI Inferred from Physical Interaction
IDA Inferred from Direct Assay
RCA Inferred from Reviewed Computational Analysis
TAS Traceable Author Statement
NAS Non-traceable Author Statement
IC Inferred by Curator
ND No biological Data available
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IEAInferred from Electronic Annotation
• Sequence Similarity (BLAST)
• Automatic transfer from mappings (InterPro2GO, EC2GO etc.)
-> Not manually reviewed
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ISSInferred from Sequence or Structural
Similarity
• Sequence similarity
• Recognized domains
• Structural similarity
-> Use of ‘with’ column recommended
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IEPInferred from Expression Pattern
• Transcript levels (Northerns, microarrays)
• Protein levels (Western blots)
-> Timing or localization of expression
-> Biological process annotations
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IMPInferred from Mutant Phenotype
• Gene mutation/knockout
• Overexpression/ectopic expression
• Anti-sense experiments
• RNAi experiments
• Specific protein inhibitors
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IGIInferred from Genetic Interaction
• Suppressors, synthetic lethals…
• Functional complementation
• Rescue experiments
->Use of ‘with’ column recommended
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IPIInferred from Physical Interaction
• 2-hybrid interactions
• Co-purification
• Co-immunoprecipitation
• Ion/complex/protein binding experiments
->Use of ‘with’ column recommended
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IDAInferred from Direct Assay
• Enzyme assays
• In vitro reconstitution (e.g. transcription)
• Immunofluorescence (for cell. comp.)
• Cell fractionation (for cell. comp.)
• Physical interaction/binding assay
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RCAInferred from Reviewed Computational
Analysis
• Non-sequence-based computational methods
• Genome-wide analyses (e.g. 2-hybrid)
• Combinations of large-scale experiments
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TASTraceable Author Statement
• Support from review article
• Textbook ‘common knowledge’
->Data that can be ‘traced’ back
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NASNon-traceable Author Statement
• Database entries that don't cite a paper
->Data that cannot be ‘traced’ back
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ICInferred by Curator
• Not supported by any direct evidence
• Inferred from other GO annotations
-> GO term in ‘with/from’ column required
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NDNo biological Data available
• molecular function unknown GO:0005554
• biological process unknown GO:0000004
• cellular component unknown GO:0008372
Curator found no information supporting any annotation
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TAS/IDA
IMP/IGI/IPI
ISS/IEP
NAS
IEA
Term Hierarchy
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Meloidogyne incognita: McCarter et al. 2003
Annotation summaries
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Mitochondrial P450
Annotation of gene products with GO terms
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Cellular component: mitochondrial inner membrane GO:0005743
Biological process:Electron transportGO:0006118
Molecular function: monooxygenase activity GO:0004497substrate + O2 = CO2 +H20 product
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Other gene products annotated to monooxygenase activity (GO:0004497)
- monooxygenase, DBH-like 1 (mouse)- prostaglandin I2 (prostacyclin) synthase (mouse)- flavin-containing monooxygenase (yeast) - ferulate-5-hydrolase 1 (arabidopsis)
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Unknown v.s. Unannotated• “Unknown” is used when the curator has
determined that there is no existing literature to support an annotation.– Biological process unknown GO:0000004– Molecular function unknown GO:0005554– Cellular component unknown GO:0008372
• NOT the same as having no annotation at all – No annotation means that no one has looked yet
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Annotation of a genome
• GO annotations are always work in progress
• Part of normal curation process
– More specific information
– Better evidence code
• Replace obsolete terms
• “Last reviewed” date
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How to access the Gene ontology and its annotations
1. Downloads • Ontologies
• Annotations : Gene association files
• Ontologies and Annotations
2. Web-based access • AmiGO (http://www.godatabase.org)
• QuickGO
(http://www.ebi.ac.uk/ego)
among others…
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Gene Ontology :
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Selected Gene Tree: pearson lw n3d ...Branch color classification:Set_LW_n3d_5p_...
Colored by: Copy of Copy of C5_RMA (Defa...Gene List: all genes (14010)
attacked
time
control
Puparial adhesionMolting cyclehemocyanin
Defense responseImmune responseResponse to stimulusToll regulated genesJAK-STAT regulated genes
Immune responseToll regulated genes
Amino acid catabolismLipid metobolism
Peptidase activityProtein catabloismImmune response
Selected Gene Tree: pearson lw n3d ...Branch color classification:Set_LW_n3d_5p_...
Colored by: Copy of Copy of C5_RMA (Defa...Gene List: all genes (14010)
Bregje Wertheim at the Centre for Evolutionary Genomics, Department of Biology, UCL and Eugene Schuster Group, EBI.
…analysis of high-throughput data according to GOMicroArray data analysis
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Anatomy
Physiology
Phenotype
Pathway
Disease
Molecular
MetabolicDevelopmental
Stage
Ontologies