GO represents concepts used to classify specific parts o

1
The Gene Ontologies
A Common Language for Annotation of Genes from
Yeast, Flies and Mice
and Plants and Worms
and Humans
and anything else!
2
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

3
Expansion of Sequence Info
4
Entering the Genome Sequencing Era
Eukaryotic Genome Sequences Year Genome
Genes Size (Mb) Yeast (S. cerevisiae) 1996
12 6,000 Worm (C. elegans) 1998
97 19,100 Fly (D. melanogaster) 2000
120 13,600 Plant (A. thaliana) 2001 125
25,500 Human (H. sapiens, 1st Draft) 2001
3000 35,000
5
Baldauf et al. (2000) Science 290972
6
Comparison of sequences from 4 organisms
MCM3
MCM2
CDC46/MCM5
CDC47/MCM7
CDC54/MCM4
MCM6
These proteins form a hexamer in the species that
have been examined
7
http//www.geneontology.org/
8
Outline of Topics

• Introduction to the Gene Ontologies (GO)
• Annotations to GO terms
• GO Tools
• Applications of GO

9
What is an Ontology? (from OED) 1721 BAILEY,
Ontology, an Account of being in the Abstract.
1733 (title) A Brief Scheme of Ontology or the
Science of Being in General. a1832 BENTHAM Fragm.
Ontol. Wks. 1843 VIII. 195 The field of ontology,
or as it may otherwise be termed, the field of
supremely abstract entities, is a yet untrodden
labyrinth. 1884 BOSANQUET tr. Lotze's Metaph. 22
Ontology..as a doctrine of the being and
relations of all reality, had precedence given to
it over Cosmology and Psychology, the two
branches of enquiry which follow the reality into
its opposite distinctive forms.
10
Sriniga Srinivasan, Chief Ontologist, Yahoo!
The ontology. Dividing human knowledge into a
clean set of categories is a lot like trying to
figure out where to find that suspenseful black
comedy at your corner video store. Questions
inevitably come up, like are Movies part of Art
or Entertainment? (Yahoo! lists them under the
latter.) -Wired Magazine, May 1996
11
The 3 Gene Ontologies

• Molecular Function elemental activity/task
• the tasks performed by individual gene products
  examples are carbohydrate binding 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 include
  nucleus, telomere, and RNA polymerase II
  holoenzyme

12
Example Gene Product hammer
Function (what) Process (why) Drive nail (into
wood) Carpentry Drive stake (into soil)
Gardening Smash roach Pest Control Clowns
juggling object Entertainment
13
Biological Examples
Molecular Function
Molecular Function
Biological Process
Biological Process
Cellular Component
Cellular Component
14
Terms, Definitions, IDs
term MAPKKK cascade (mating sensu
Saccharomyces) goid GO0007244 definition
OBSOLETE. MAPKKK cascade involved in transduction
of mating pheromone signal, as described in
Saccharomyces. definition_reference
PMID9561267 comment This term was made
obsolete because it is a gene product specific
term. To update annotations, use the biological
process term 'signal transduction during
conjugation with cellular fusion GO0000750'.
definition MAPKKK cascade involved in
transduction of mating pheromone signal, as
described in Saccharomyces
15
Directed Cyclic Graph
Figure 4.1. Life cycles of heterothallic and
homothallic strains of S. cerevisiae.
Heterothallic strains can be stably maintained as
diploids and haploids, whereas homothallic
strains are stable only as diploids, because the
transient haploid cells switch their mating type,
and mate.
An Introduction to the Genetics and Molecular
Biology of the Yeast Saccharomyces cerevisiae
Fred Sherman 2000 Modified from F. Sherman,
Yeast genetics. The Encyclopedia of Molecular
Biology and Molecular Medicine, pp. 302-325, Vol.
6. Edited by R. A. Meyers, VCH Pub., Weinheim,
Germany,1997.
16
Parent-Child Relationships
Nucleus
Nuclear envelope
Nucleoplasm
Chromosome
Perinuclear space
Nucleolus
A child is a subset of a parents elements
The cell component term Nucleus has 5 children
17
Tree Relationships
Derivation of Romance languages from Latin. From
R.A. Hall Jr., Introductory Linguistics
originally published by Chilton Books, now
distributed by Rand McNally Co.
18
Ontology Relationships
Directed Acyclic Graph
http//www.ebi.ac.uk/ego
19
Evidence Codes for GO Annotations
http//www.geneontology.org/doc/GO.evidence.html
20
IEA Inferred from Electronic Annotation ISS Inferr
ed 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-tr
aceable Author Statement IC Inferred by
Curator ND No biological Data available
21
IEAInferred from Electronic Annotation

• Sequence Similarity (BLAST)
• Automatic transfer from mappings
  (InterPro2GO, EC2GO etc.)
• -gt Not manually reviewed

22
ISSInferred from Sequence or Structural
Similarity

• Sequence similarity
• Recognized domains
• Structural similarity
• -gt Use of with column recommended

23
IEPInferred from Expression Pattern

• Transcript levels (Northerns, microarrays)
• Protein levels (Western blots)
• -gt Timing or localization of expression
• -gt Biological process annotations

24
IMPInferred from Mutant Phenotype

• Gene mutation/knockout
• Overexpression/ectopic expression
• Anti-sense experiments
• RNAi experiments
• Specific protein inhibitors

25
IGIInferred from Genetic Interaction

• Suppressors, synthetic lethals
• Functional complementation
• Rescue experiments
• -gt Use of with column recommended

26
IPIInferred from Physical Interaction

• 2-hybrid interactions
• Co-purification
• Co-immunoprecipitation
• Ion/complex/protein binding experiments
• -gt Use of with column recommended

27
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

28
RCAInferred from Reviewed Computational Analysis

• Non-sequence-based computational methods
• Genome-wide analyses (e.g. 2-hybrid)
• Combinations of large-scale experiments

29
TASTraceable Author Statement

• Support from review article
• Textbook common knowledge
• -gt Data that can be traced back

30
NASNon-traceable Author Statement

• Database entries that don't cite a paper
• -gt Data that cannot be traced back

31
ICInferred by Curator

• Not supported by any direct evidence
• Inferred from other GO annotations
• -gt GO term in with/from column required

32
NDNo biological Data available
Curator found no information supporting any
annotation

• molecular function unknown GO0005554
• biological process unknown GO0000004
• cellular component unknown GO0008372

33
Term Hierarchy
TAS/IDA IMP/IGI/IPI ISS/IEP NAS IEA
34
Qualifiers
The qualifier modifies the interpretation of a GO
term
NOT explicit note that a gene product is not
associated with a GO term colocalizes_with
only transient localization, or low resolution of
an assay contributes_to gene product that is
part of a complex can be annotated to the
process/function of the complex
http//www.geneontology.org/GO.annotation.shtmlqu
al
35
http//www.geneontology.org/doc/GO.evidence.html