1. The Gene Ontology Project
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The Gene Ontology Project
An Introduction

2. There is a lot
of biological
research output.
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3. Search on
mesoderm
development…
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4. You get 6752 results! How will you ever find what you want? Another
example…
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5. How will you spot the patterns?
attacked
time
control
Microarray data
shows changed
expression of
thousands of genes.
How will you spot the patterns?
Bregje Wertheim at the Centre for Evolutionary Genomics, Department of Biology, UCL and Eugene Schuster Group, EBI.
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6. Scientists work hard. 19/09/18
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7. There are lots of papers to read. 19/09/18
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8. more
every
week.
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9. and more… 19/09/18 http://www.teamtechnology.co.uk/f-scientist.jpg
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10. more and more and more! 19/09/18
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11. Help! Help! more and more and more! 19/09/18
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12. Ontology is a way to capture knowledge in a written and computable form.
Computable means that the computer finds patterns
so we don’t have to.
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13. Demo and practical work
Ebay search
(keyword ‘lead’) v.
Pubmed search
(keyword ‘flower’)
Demo and practical work
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14. The Gene Ontology
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15. This is our
browser.
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16. Search on
mesoderm
development.
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17. Here is
mesoderm
development.
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18. Definition of
mesoderm
development.
Gene products
involved in
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19. There are many gene products involved in mesoderm development.
But fewer gene
products than
papers.
You can read
papers describing
what is known
about them.
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20. 19/09/18

21. time
attacked
control
Bregje Wertheim at the Centre for Evolutionary Genomics, Department of Biology, UCL and Eugene Schuster Group, EBI.
19/09/18

22. See which processes are upregulated or downregulated.
time
Defense response
Immune response
Response to stimulus
Toll regulated genes
JAK-STAT regulated genes
Puparial adhesion
Molting cycle
hemocyanin
Amino acid catabolism
Lipid metobolism
Peptidase activity
Protein catabloism
Immune response
Immune response
Toll regulated genes
attacked
control
Bregje Wertheim at the Centre for Evolutionary Genomics, Department of Biology, UCL and Eugene Schuster Group, EBI.
19/09/18

23. Did you find your favourite gene product or process?
Practical work:
Search AmiGO
Did you find your favourite
gene product or process?
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24. How does the Gene Ontology work?
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25. 19/09/18

26. term: transcription initiation
The Gene Ontology
is like a dictionary
term: transcription initiation
id: GO:
definition: Processes involved
in the assembly of the RNA
polymerase complex at the
promoter region of a DNA
template resulting in the
subsequent synthesis of
RNA from that promoter.
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27. The whole system. Clark et al., 2005 is_a part_of
The gene ontology consortium develops ontologies and makes annotation of gene products to those ontologies. The ontologies are databases containing sets of biological processes, molecular functions, and cellular components and the relationships between them. Annotators within the consortium use these ontologies to categorise gene products. During my talk today I’m going to explain about the uses of GO and give a more detailed explanation of the ontolgoies and of the system of annotation. Then Harold Drabkin is going to talk in more detail about annotation and about how you can submit annotations of your own gene products of interest.
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28. Mitochondrial P450 (CC24 PR01238; MITP450CC24) An example…
This is a gene product that has already been annotated to all three gene ontologies. It is the Mitochondrial P450 gene product.
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29. Where is it? Mitochondrial p450 mitochondrial inner membrane
The mitochondrial p450 gene products are localised on the mitochondrial inner membrane and the GO cellular component term for this is mitochondrial inner membrane ; GO:
mitochondrial inner
membrane
GO cellular component term:
GO:
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30. substrate + O2 = CO2 +H20 product
What does it do?
substrate + O2 = CO2 +H20 product
The function of the gene product is described by the GO molecular function term:
monooxygenase activity ; GO:
monooxygenase activity
GO molecular function term:
GO:
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31. Which process is this? electron transport ; GO:0006118
The process in which the gene product is involved is GO biological process term:
electron transport ; GO:
In this way you can see that many aspects of a single gene product can be recorded simply by annotating it to the three ontologies.
electron transport
GO biological process term:
GO:
mitochondrion/krebpic.html
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32. The whole system. Clark et al., 2005 is_a part_of
The gene ontology consortium develops ontologies and makes annotation of gene products to those ontologies. The ontologies are databases containing sets of biological processes, molecular functions, and cellular components and the relationships between them. Annotators within the consortium use these ontologies to categorise gene products. During my talk today I’m going to explain about the uses of GO and give a more detailed explanation of the ontolgoies and of the system of annotation. Then Harold Drabkin is going to talk in more detail about annotation and about how you can submit annotations of your own gene products of interest.
19/09/18

33. The Gene Ontology is for all species some language barriers.
and that means
we have to
*bridge*
some language barriers.
The gene ontology consortium develops ontologies and makes annotation of gene products to those ontologies. The ontologies are databases containing sets of biological processes, molecular functions, and cellular components and the relationships between them. Annotators within the consortium use these ontologies to categorise gene products. During my talk today I’m going to explain about the uses of GO and give a more detailed explanation of the ontolgoies and of the system of annotation. Then Harold Drabkin is going to talk in more detail about annotation and about how you can submit annotations of your own gene products of interest.
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34. Same name, same thing? Bridge of Sighs, Cambridge. Ponte dei Sospiri,
Bridge of Sighs,
Cambridge.
Ponte dei Sospiri,
Venice.
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35. ? Taction Tactition Tactile sense In biology…
In developing the ontologies we are solving a number of problems biologists.
Currently in biology there are many ambiguities in language. Groups of researchers may use the same words to mean different things, or they may use several different words to refer to the same thing. This causes problems for scientists trying to access research carried out by groups outside their immediate field. It also makes it very difficult to process biological information using a computer.
For example three groups of biologists studying different model organisms may all be studying the perception of touch. Scientists in different groups might talk about this single process as ‘tactition’, ‘tactile sense’ or ‘taction’. This differing use of language means that when they try to find and read each other’s papers they will have more trouble. It will also be harder for them to use a computer to find and interpret biological data on this subject since the computer has no way to know that these words mean the same thing.
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36. perception of touch ; GO:0050975
Taction
Tactition
Tactile sense
perception of touch ; GO:
The GO provides a solution to this problem since we take biological concepts like the perception of touch and we make them a single GO item in the ontology. We add all the relevant synonyms, and give a unique numerical identifier to the concept.
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37. Bud initiation?
The GO also provides a solution to the opposite problem in which several groups of scientists use the same words to refer to different things. For example the phrase ‘bud inititation’ could refer to the initiation of a tooth bud, a yeast reproductive bud, or a bud on a tree. However, these three types of bud are initiated in quite different ways, and scientists would like to be able to distinguish between them.
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38. = reproductive bud initiation
= tooth bud initiation
= reproductive bud initiation
To solve this problem the GO differentiates between differing concepts by adding a ‘sensu ending’. So according to this example, we would have ‘bud initiation sensu Metazoa’ to mean the kind of bud initation that gives rise to a tooth in mammals. We would have ‘bud initiation sensu Saccharomyces’ for the initation of a reproductive bud in yeast, and we would have ‘bud initiation sensu Viridiplantae’ for the initation of a tree bud. This means that gene products involved in bud initiation can be categorised along with only those other gene products involved in the same kind of bud initation.
= branch bud initiation
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39. Demo:
Writing an ontology
The car ontology
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40. Demo: The gene ontology
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41. Categorization of gene products using GO is called annotation.
So how does that happen?
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42. Choose your favourite gene.
P05147
Choose your favourite gene.
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43. P05147
Find a paper
about it.
PMID:
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44. Find the GO term describing its function, process
PMID:
Find the GO
term describing its
function, process
or location of action.
GO:
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45. IDA What evidence do they show? P05147 PMID: 2976880 GO:0047519
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46. P05147 GO:0047519 IDA PMID:2976880 Write these down… IDA P05147
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47. Send to the GO Consortium.
Send to the GO Consortium
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48. Finding annotations in a paper
…for B. napus PERK1 protein (Q9ARH1)
In this study, we report the isolation and molecular characterization of the B. napus PERK1 cDNA, that is predicted to encode a novel receptor-like kinase. We have shown that like other plant RLKs, the kinase domain of PERK1 has serine/threonine kinase activity, In addition, the location of a PERK1-GTP fusion protein to the plasma membrane supports the prediction that PERK1 is an integral membrane protein…these kinases have been implicated in early stages of wound response…
serine/threonine kinase activity,
integral membrane protein
wound response
PubMed ID:
…piece of text…from which can pull out GO terms
Function: protein serine/threonine kinase activity GO:
Component: integral to plasma membrane GO:
Process: response to wounding GO:
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Annotation details

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51. 19/09/18

52. Where to get annotations?
Non-redundant species database
Contains all GO annotations for given species + other information.
Multispecies database - GOA
Contains all GO annotations.
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53. Evidence codes
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54. IDA - inferred from direct assay Enzyme assays
In vitro reconstitution (e.g. transcription)
Immunofluorescence (for cellular component)
Cell fractionation (for cellular component)
Physical interaction/binding
IEP - inferred from expression pattern
Transcript levels (e.g. Northerns, microarray data)
Protein levels (e.g. Western blots)
IGC - inferred from genomic context
Operon structure
Syntenic regions
Pathway analysis
Genome-scale analysis of processes
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55. IGI - inferred from genetic interaction
"Traditional" genetic interactions such as suppressors, synthetic lethals, etc.
Functional complementation
Rescue experiments
Inference about one gene drawn from the phenotype of a mutation
in a different gene.
IMP - inferred from mutant phenotype
Any gene mutation/knockout
Overexpression/ectopic expression of wild-type or mutant genes
Anti-sense experiments
RNAi experiments
Specific protein inhibitors
Polymorphism or allelic variation
IPI - inferred from physical interaction
2-hybrid interactions
Co-purification
Co-immunoprecipitation
Ion/protein binding experiments
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56. ISS - inferred from sequence or structural similarity
Sequence similarity (homologue of/most closely related to)
Recognized domains
Structural similarity
Southern blotting
RCA - inferred from reviewed computational analysis
Large-scale protein-protein interaction experiments
Microarray experiments
Integration of large-scale datasets of several types
Text-based computation
IEA - Inferred from Electronic Annotation
NAS - non-traceable author statement
ND - no biological data available
TAS - traceable author statement
NR - not recorded
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57. Should we trust electronic annotations?
PMID:
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58.
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59. 19/09/18

60. ec2go mapping !version: $Revision: 1.67 $
!date: $Date: 2008/01/21 11:29:01 $
!Mapping of GO function_ontology "enzymes" to Enzyme Commission Numbers.
!original mapping by Michael Ashburner, Cambridge.
!This version parsed from function.ontology on 2008/01/15 14:01:16
!by Daniel Barrell, EBI, Hinxton !
EC:1 > GO:oxidoreductase activity ; GO:
EC:1.1 > GO:oxidoreductase activity, acting on CH-OH group of donors ; GO:
EC:1.1.1 > GO:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor ; GO:
EC: > GO:alcohol dehydrogenase activity ; GO:
EC: > GO:L-xylulose reductase activity ; GO:
EC: > GO:3-oxoacyl-[acyl-carrier-protein] reductase activity ; GO:
EC: > GO:acylglycerone-phosphate reductase activity ; GO:
EC: > GO:3-dehydrosphinganine reductase activity ; GO:
EC: > GO:L-threonine 3-dehydrogenase activity ; GO:
EC: > GO:4-oxoproline reductase activity ; GO:
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61. interpro2go mapping InterPro is a database of protein families,
domains and functional sites in which identifiable
features found in known proteins can be applied
to unknown protein sequences.
!date: 2008/01/15 13:01:24
!Mapping of InterPro entries to GO
!Nicola Mulder, Hinxton !
InterPro:IPR Retinoid X receptor > GO:DNA binding ; GO:
InterPro:IPR Retinoid X receptor > GO:steroid binding ; GO:
InterPro:IPR Retinoid X receptor > GO:regulation of transcription, DNA-dependent ; GO:
InterPro:IPR Retinoid X receptor > GO:nucleus ; GO:
InterPro:IPR Helix-turn-helix, AraC type > GO:transcription factor activity ; GO:
InterPro:IPR Helix-turn-helix, AraC type > GO:intracellular ; GO:
InterPro:IPR Metallothionein, vertebrate > GO:metal ion binding ; GO:
InterPro:IPR Peptidase M7, snapalysin > GO:extracellular region ; GO:
InterPro:IPR PAS > GO:signal transducer activity ; GO:
InterPro:IPR Fimbrial biogenesis outer membrane usher protein > GO:transporter activity ; GO:
InterPro:IPR P2Y4 purinoceptor > GO:purinergic nucleotide receptor activity, G-protein coupled ; GO:
InterPro:IPR Anaphylatoxin/fibulin > GO:extracellular region ; GO:
InterPro:IPR Hok/gef cell toxic protein > GO:membrane ; GO:
InterPro:IPR Carboxyl transferase > GO:ligase activity ; GO:
InterPro:IPR Phosphofructokinase > GO:6-phosphofructokinase activity ; GO:
InterPro:IPR Melatonin receptor > GO:integral to membrane ; GO:
InterPro:IPR Guanine-specific ribonuclease N1 and T1 > GO:endoribonuclease activity ; GO:
InterPro:IPR Chloroperoxidase > GO:peroxidase activity ; GO:
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62. electronic annotation appears in QuickGO.
Manual annotation
appears in AmiGO.
Manual and
electronic annotation
appears in QuickGO.
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63. Many species groups annotate. We see the research of one
Clark et al., 2005
Many species
groups annotate.
We see the
research of one
function across
all species.
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64. Search for your favourite gene and see if the annotation
Exercise:
Search for your favourite gene
and see if the annotation
is electronic or manual.
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65. Submit new GO terms:
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66. 19/09/18

67. 19/09/18
GO slims

68. Clark et al., 2005 is_a part_of
The gene ontology consortium develops ontologies and makes annotation of gene products to those ontologies. The ontologies are databases containing sets of biological processes, molecular functions, and cellular components and the relationships between them. Annotators within the consortium use these ontologies to categorise gene products. During my talk today I’m going to explain about the uses of GO and give a more detailed explanation of the ontolgoies and of the system of annotation. Then Harold Drabkin is going to talk in more detail about annotation and about how you can submit annotations of your own gene products of interest.
19/09/18

69. Clark et al., 2005 is_a part_of
The gene ontology consortium develops ontologies and makes annotation of gene products to those ontologies. The ontologies are databases containing sets of biological processes, molecular functions, and cellular components and the relationships between them. Annotators within the consortium use these ontologies to categorise gene products. During my talk today I’m going to explain about the uses of GO and give a more detailed explanation of the ontolgoies and of the system of annotation. Then Harold Drabkin is going to talk in more detail about annotation and about how you can submit annotations of your own gene products of interest.
19/09/18

70. Whole genome analysis (J. D. Munkvold et al., 2004)
The GO can be used for further very specific applications in the lab. For example in microarray analysis you can use the GO data to show which processes are modified by the treatment being studied in a given microarray experiment. You can also use the GO to give an overview of the range of gene products in a whole genome as represented by the functions of processes those genes are involved in.
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71. …analysis of high-throughput data according to GO
time
Puparial adhesion
Molting cycle
hemocyanin
Amino acid catabolism
Lipid metobolism
Peptidase activity
Protein catabloism
Immune response
Immune response
Toll regulated genes
attacked
control
Bregje Wertheim at the Centre for Evolutionary Genomics, Department of Biology, UCL and Eugene Schuster Group, EBI.
19/09/18

72. Making Slims: OBO-Edit
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73. Reapplying slimmed ontology to annotations: AmiGO http://amigo
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74. Converting IDs: PICR http://www.ebi.ac.uk/Tools/picr/
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75. GOOSE http://www.berkeleybop.org/goose
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76. U.S. Virgin Islands, March 30 - April 3, 2006
2006 Consortium Meeting,
St. Croix,
U.S. Virgin Islands, March 30 - April 3, 2006
Finally, this is the current list of groups in the consortium. The Editorial office where the ontologies are developed is in Cambridge in the UK, and the rest of these groups contribute annotations. We are keen to include more groups in the annotation process so that more species will be manually annotated to the go and so Harold Drabkin is now going to talk about the process of annotation and about how you can contribute manual annotations of your own gene products.
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77. E. Coli hub
Reactome
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