1. GO and OBO: an introduction

2. Jane Lomax EMBL-EBI What is the Gene Ontology? What is OBO? OBO-Edit demo & practical What is the Gene Ontology? What is OBO? OBO-Edit demo & practical

3. Jane Lomax EMBL-EBI Gene Ontology Built for a very specific purpose: “annotation of genes and proteins in genomic and protein databases” Applicable to all species Built for a very specific purpose: “annotation of genes and proteins in genomic and protein databases” Applicable to all species

4. Jane Lomax EMBL-EBI Evolution of GO Original GO created in 2000 Three databases involved: –FlyBase (Drosophila) –MGI (Mouse) –SGD (S. cerevisae) Used immediately Original GO created in 2000 Three databases involved: –FlyBase (Drosophila) –MGI (Mouse) –SGD (S. cerevisae) Used immediately

5. Jane Lomax EMBL-EBI Evolution of GO Later databases: –TAIR (Arabadopsis) –TIGR (microbes including prokaryotes) –SWISS-PROT (several thousand species inc. human) –PSU (P. falciparum) Recent additions –ZFIN (zebrafish) –PAMGO (plant pathogens) Later databases: –TAIR (Arabadopsis) –TIGR (microbes including prokaryotes) –SWISS-PROT (several thousand species inc. human) –PSU (P. falciparum) Recent additions –ZFIN (zebrafish) –PAMGO (plant pathogens)

6. Jane Lomax EMBL-EBI Evolution of GO GO development traditionally annotation-driven –development directed by use Terms added as new species annotated Terms added on as as-needed basis GO development traditionally annotation-driven –development directed by use Terms added as new species annotated Terms added on as as-needed basis

7. Jane Lomax EMBL-EBI Evolution of GO Developed by an international consortium of biologists and computer scientists –members from individual databases –central office at EBI Development involves collaboration with domain experts from different biological fields –also formal ontologists Developed by an international consortium of biologists and computer scientists –members from individual databases –central office at EBI Development involves collaboration with domain experts from different biological fields –also formal ontologists

8. Jane Lomax EMBL-EBI Evolution of GO Resulted in ‘organic’ structure, little formality Ontological formality added subsequently –philosophical and logical Resulted in ‘organic’ structure, little formality Ontological formality added subsequently –philosophical and logical

9. Jane Lomax EMBL-EBI Growth of GO

10. Jane Lomax EMBL-EBI How does GO work? What does the gene product do? Where and when does it act? Why does it perform these activities? What does the gene product do? Where and when does it act? Why does it perform these activities? What information might we want to capture about a gene product?

11. Jane Lomax EMBL-EBI GO structure GO terms divided into three parts: –cellular component –molecular function –biological process GO terms divided into three parts: –cellular component –molecular function –biological process

12. Cellular Component where a gene product acts

13. Cellular Component

15. Enzyme complexes in the component ontology refer to places, not activities.

16. Molecular Function activities or “ jobs ” of a gene product glucose-6-phosphate isomerase activity

17. Molecular Function insulin binding insulin receptor activity insulin binding insulin receptor activity

18. Molecular Function drug transporter activity

19. Jane Lomax EMBL-EBI Molecular Function A gene product may have several functions; a function term refers to a single reaction or activity, not a gene product. Sets of functions make up a biological process. A gene product may have several functions; a function term refers to a single reaction or activity, not a gene product. Sets of functions make up a biological process.

20. Biological Process a commonly recognized series of events cell division

21. Biological Process transcription

22. Biological Process regulation of gluconeogenesis

23. Biological Process limb development

24. Biological Process courtship behavior

25. Jane Lomax EMBL-EBI Ontology Structure Terms are linked by two relationships –is-a  –part-of  Terms are linked by two relationships –is-a  –part-of 

26. Jane Lomax EMBL-EBI Ontology Structure cell membrane chloroplast mitochondrial chloroplast membrane is-a part-of

27. Jane Lomax EMBL-EBI 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 Ontologies are structured as a hierarchical directed acyclic graph (DAG) Terms can have more than one parent and zero, one or more children

28. Jane Lomax EMBL-EBI Ontology Structure cell membrane chloroplast mitochondrial chloroplast membrane Directed Acyclic Graph (DAG) - multiple parentage allowed

29. Jane Lomax EMBL-EBI Open Biomedical Ontologies (OBO) GO is a member of OBO An umbrella project for grouping different ontologies in biological/medical field –a repository for ontologies with defined set of standards Available from a single source: http://obo.sourceforge.net/ GO is a member of OBO An umbrella project for grouping different ontologies in biological/medical field –a repository for ontologies with defined set of standards Available from a single source: http://obo.sourceforge.net/

30. Jane Lomax EMBL-EBI Why do we need OBO? GO covers small area of biology: –molecular function of a protein –biological function of a protein –cellular location of a protein GO covers small area of biology: –molecular function of a protein –biological function of a protein –cellular location of a protein

31. Jane Lomax EMBL-EBI Why do we need OBO? Lots of other aspects that also need to be captured, e.g.: –phenotype –anatomy –genomic –taxonomy Lots of other aspects that also need to be captured, e.g.: –phenotype –anatomy –genomic –taxonomy

32. Jane Lomax EMBL-EBI Why do we need OBO? Many groups develop their own ontologies –e.g. plant ontology, anatomies for specific organisms No standardisation of ontologies with respect to: –format –scope –relationships No way of knowing whether such ontologies already exist No mechanism of distribution for other groups Many groups develop their own ontologies –e.g. plant ontology, anatomies for specific organisms No standardisation of ontologies with respect to: –format –scope –relationships No way of knowing whether such ontologies already exist No mechanism of distribution for other groups

33. Jane Lomax EMBL-EBI Why do we need OBO? Creating ontologies takes a lot of work –Makes sense to reuse existing ontologies where possible Improves data integration where small set of ontologies used Allows ontologies to be made available from a single place Creating ontologies takes a lot of work –Makes sense to reuse existing ontologies where possible Improves data integration where small set of ontologies used Allows ontologies to be made available from a single place

34. Jane Lomax EMBL-EBI Why do we need OBO? Ultimate aim: a complete set of integrated ontologies completely covering the biomedical domain

35. Jane Lomax EMBL-EBI OBO requirements To be part of OBO, ontologies must: Be open, can be used by all without any constraint To be part of OBO, ontologies must: Be open, can be used by all without any constraint

36. Jane Lomax EMBL-EBI OBO requirements: open Ontologies can be used by anyone without any constraints, except: –original authors are acknowledged –cannot be edited and then released under same name Ontologies can be used by anyone without any constraints, except: –original authors are acknowledged –cannot be edited and then released under same name

37. Jane Lomax EMBL-EBI OBO requirements To be part of OBO, ontologies must: Be open, can be used by all without any constraint Be in a common shared syntax To be part of OBO, ontologies must: Be open, can be used by all without any constraint Be in a common shared syntax

38. Jane Lomax EMBL-EBI OBO requirements: syntax Usually the OBO format, same as primary GO format –and adaptions of OBO format Also accept OWL (Web Ontology Language) format Allows the same tools to be applied, facilitating shared software implementations Usually the OBO format, same as primary GO format –and adaptions of OBO format Also accept OWL (Web Ontology Language) format Allows the same tools to be applied, facilitating shared software implementations

39. Jane Lomax EMBL-EBI Anatomy of an OBO term id: GO:0006094 name: gluconeogenesis namespace: process def: The formation of glucose from noncarbohydrate precursors, such as pyruvate, amino acids and glycerol. [http://cancerweb.ncl.ac.uk/omd/index.html] exact_synonym: glucose biosynthesis xref_analog: MetaCyc:GLUCONEO-PWY is_a: GO:0006006 is_a: GO:0006092 id: GO:0006094 name: gluconeogenesis namespace: process def: The formation of glucose from noncarbohydrate precursors, such as pyruvate, amino acids and glycerol. [http://cancerweb.ncl.ac.uk/omd/index.html] exact_synonym: glucose biosynthesis xref_analog: MetaCyc:GLUCONEO-PWY is_a: GO:0006006 is_a: GO:0006092 unique ID term name definition synonym database ref parentage ontology

40. Jane Lomax EMBL-EBI OBO requirements To be part of OBO, ontologies must: Be open, can be used by all without any constraint Be in a common shared syntax Not overlap with other ontologies in OBO To be part of OBO, ontologies must: Be open, can be used by all without any constraint Be in a common shared syntax Not overlap with other ontologies in OBO

41. Jane Lomax EMBL-EBI OBO requirements: overlapping Ontologies can (and should) overlap partially, but large overlap should be avoided Idea is that terms from different ontologies can be combined to form new terms Striving for accepted standards rather than competition Ontologies can (and should) overlap partially, but large overlap should be avoided Idea is that terms from different ontologies can be combined to form new terms Striving for accepted standards rather than competition

42. Jane Lomax EMBL-EBI OBO requirements To be part of OBO, ontologies must: Be open, can be used by all without any constraint Be in a common shared syntax Not overlap with other ontologies in OBO Share a unique identifier space To be part of OBO, ontologies must: Be open, can be used by all without any constraint Be in a common shared syntax Not overlap with other ontologies in OBO Share a unique identifier space

43. Jane Lomax EMBL-EBI OBO requirements: id space So, for example, the GO identifier is “GO”: –No other OBO ontology could use this id space Prevents problems where multiple ontologies are used together So, for example, the GO identifier is “GO”: –No other OBO ontology could use this id space Prevents problems where multiple ontologies are used together

44. Jane Lomax EMBL-EBI OBO requirements To be part of OBO, ontologies must: Be open, can be used by all without any constraint Be in a common shared syntax Not overlap with other ontologies in OBO Share a unique identifier space Include text definitions of their terms To be part of OBO, ontologies must: Be open, can be used by all without any constraint Be in a common shared syntax Not overlap with other ontologies in OBO Share a unique identifier space Include text definitions of their terms

45. Jane Lomax EMBL-EBI OBO requirements In addition, OBO includes ontology of relationships –all ontologies should use these definitions of relationships For example –part_of –develops_from –regulates In addition, OBO includes ontology of relationships –all ontologies should use these definitions of relationships For example –part_of –develops_from –regulates

46. Jane Lomax EMBL-EBI What’s available demo: http://obo.sourceforge.net/ demo: http://obo.sourceforge.net/

47. Jane Lomax EMBL-EBI Editing ontologies GO is edited using OBO-Edit –stand-alone Java application –available for all platforms –browse, create or edit any ontology in OBO format GO is edited using OBO-Edit –stand-alone Java application –available for all platforms –browse, create or edit any ontology in OBO format

48. Jane Lomax EMBL-EBI OBO-Edit demo Browsing ontologies –loading ontologies (including loading multiple ontologies) –graph viewer –reasoner/single relationship views –searching/filtering/rendering –help Creating/editing ontologies –creating a new ontology –adding terms –copying/moving/deleting terms –adding definitions, dbxrefs etc –verification plugin –saving ontologies Browsing ontologies –loading ontologies (including loading multiple ontologies) –graph viewer –reasoner/single relationship views –searching/filtering/rendering –help Creating/editing ontologies –creating a new ontology –adding terms –copying/moving/deleting terms –adding definitions, dbxrefs etc –verification plugin –saving ontologies