BioPAX (an introduction) Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012 (http://sgtp.net/AndreaSplendiani)

1. BioPAX (an introduction)
Andrea Splendiani
(BioPAX editor)
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

2. BioPAX (an introduction)
•What
•How
•Why
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

3. BioPAX: Biological Pathway Exchange (language)
•What is BioPAX ?
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

4. BioPAX: Biological Pathway Exchange (language)
•What is BioPAX ?
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

5. BioPAX: Biological Pathway Exchange (language)
•What is a pathway ?
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

6. Examples: biochemical pathway
• Regular
structure
• Enzymatic
activity
Source: http://www.genome.jp
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

7. Examples: signaling pathway
• Semi-regular
structure
• Activation/
inhibition
• Compartments
• “Antigen”
Source: http://www.genome.jp
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

8. Example: wikipathways
• Well defined
set of
relations and
symbols
Source:
http://www.wikipathways.org/index.php/Pathway:WP49
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

9. Example: “informal” descriptions
Sources:
http://www.biocarta.com
http://www.singulex.com/images/cytokine_pathway_Th1.png
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

10. Example: SBML
• Pathway a set
of reactions
• Dynamic
aspects/
modeling
Source: http://www.biomodels.net
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

11. Example: SBML
• Pathway a set
of reactions
• Dynamic
aspects/
modeling
Source: http://www.biomodels.net
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

12. Example: SBML
• Pathway a set
of reactions
• Dynamic
aspects/
modeling
Source: http://www.biomodels.net
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

13. Example: SBGN
• Systems Biology
Graphic Notation:
• Process Description
• Entity Relationship
• Activity Flow
Source: http://www.sbgn.org
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

14. Example: “Reactome”
• One big reaction
network instead
of pathways
Source:
http://web.expasy.org/cgi-bin/pathways/show_thumbnails.pl
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

15. Example: network biology
• Interactome
• p-p interactions
• genetic interactions
Source:
http://nd.edu/~networks/Image%20Gallery/gallery.htm#Biological
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

16. Example: Gene Ontology
• GO: Biological Process
Source:
http://www.sciencedirect.com/science/article/pii/S0012160611001758
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

17. What is a pathway ?
• Pathways can be different kind of systems: biochemical reaction
networks, signaling networks, “abstract” interaction networks
• Detailed description vs coarse descriptions (kegg vs GO)
• Static maps vs dynamic systems (Kegg vs SBML)
• Pathways vs holistic view of of interactions
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

18. What is BioPAX ?
• Biological Pathway Exchange Language:
• A language to represent different types of
pathways
• A language to enable interoperability of
different pathway representations
• = Integration
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

19. What is BioPAX ?
• Biological Pathway Exchange Language:
• A language to represent different types of
pathways
• A language to enable interoperability of
different pathway representations
• = Integration
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

20. What is BioPAX ?
•Pathways and
computation
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

21. Example: over-representation analysis
• Correlation between
processes (annotation)
and experimental
evidence
Andrea Splendiani
Source:
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
http://www.springerimages.com/Images/LifeSciences/5-10.1186_1471-2229-10-85-7
martedì 22 ottobre 13

22. Example: network analysis
• Clustering
• Centrality measures
(betweeness)
• Systems properties
(scale free networks)
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

23. Example: dynamic simulations
Source:
http://www.ebi.ac.uk/biomodels-main/static-pages.do?page=ModelMonth%2F2007-02
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

24. Pathway languages and computation
A slide to note
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

25. Pathway languages and computation
A slide to note
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

26. Pathway languages and computation
• Are same nodes
distinct across paths ?
• All paths, or at least
one path ?
A slide to note
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

27. What is BioPAX ?
• A language that can represent different representation of pathways in an
integrated way
• A language that allows computability of pathway representations
• Pathway Exchange -> Integration + Computability
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

28. What is BioPAX ?
• A language that can represent different representation of pathways in an
integrated way
• A language that allows computability of pathway representations
• Pathway Exchange -> Integration + Computability
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

29. Pathway representation trade-offs
• BioPAX focus on
integration, not
simulation
• Qualitative
models
• Captures
evidence,
provenance
• Easy to be lost
in translation!
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

30. Pathway representation trade-offs
• BioPAX focus on
integration, not
simulation
• Qualitative
models
• Captures
evidence,
provenance
• Easy to be lost
in translation!
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

31. BioPAX: community
• BioPAX is a community project (www.biopax.org) - database providers • Release of BioPAX has been articulated in levels:
• Level 1: Metabolic networks, 2004
• Level 2: Interaction (evidence, DNA), 2005
• Level 3: Signaling (states, generic entities, gene regulation, genetic
interactions), 2010
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

32. BioPAX: Biological Pathway Exchange (language)
•How ?
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

33. Describing pathways in BioPAX:
a bottom up example
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

34. Describing pathways in BioPAX:
a bottom up example
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

35. Describing pathways in BioPAX:
a bottom up example
• Using RDF
• Vocabularies (rdf, biopax,...)
• Equivalent to triples
re:res1 rdf:type bp:BiochemicalReaction
re:res1 bp:displayName “Digestion...”^^xsd:String
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

36. Describing pathways in BioPAX:
a bottom up example
• Biochemical reaction and
reactants
• Annotations
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

37. Describing pathways in BioPAX:
a bottom up example
• Entity in
context
and entity
reference
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

38. Describing pathways in BioPAX:
a bottom up example
• Entity in
context
and entity
reference
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

39. Describing pathways in BioPAX:
a bottom up example
• Entity in
context
and entity
reference
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

40. Describing pathways in BioPAX:
a bottom up example
• Representation of
catalysis
• Entity references
• Types
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

41. Describing pathways in BioPAX:
a bottom up example
• Representation of
catalysis
• Entity references
• Types
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

42. Describing pathways in BioPAX:
a bottom up example
• Representation of
catalysis
• Entity references
• Types
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

43. Describing pathways in BioPAX:
a bottom up example
• Representation of
catalysis
• Entity references
• Types
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

44. Describing pathways in BioPAX:
a bottom up example
• Representation of
catalysis
• Entity references
• Types
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

45. Describing pathways in BioPAX:
a bottom up example
• Representation of
catalysis
• Entity references
• Types
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

46. Describing pathways in BioPAX:
a bottom up example
• Representation of
catalysis
• Entity references
• Types
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

47. Describing pathways in BioPAX:
a bottom up example
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

48. Describing pathways in BioPAX:
a bottom up example
• Abstraction
• Integrated view of
different
representations
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

49. Describing pathways in BioPAX:
a bottom up example
• Abstraction
• Integrated view of
different
representations
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

50. Describing pathways in BioPAX:
a bottom up example
• Meta description
(computability)
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

51. Describing pathways in BioPAX:
a bottom up example
• Meta description
(computability)
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

52. • Biological facts
• Structure of the
pathway
• Getting it into triples...
• Structure of the
language
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

53. What is BioPAX ?
• BioPAX is a language, expressed in OWL, to represent pathways
• BioPAX expresses pathways in RDF
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

54. A Top Down view of BioPAX: classes
• Entities:
• Physical entities
• Pathways
• Interactions
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

55. A Top Down view of BioPAX: classes
• Utility classes:
• Xrefs
• Vocabularies
• Entity References
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

56. A Top Down view of BioPAX: properties
• Object properties
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque-Tecnológico de Bizkaia - Nov. 7th 2012
Bilbao Nov. 7th 2012
martedì 22 ottobre 13

57. A Top Down view of BioPAX: properties
• Object properties
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque-Tecnológico de Bizkaia - Nov. 7th 2012
Bilbao Nov. 7th 2012
martedì 22 ottobre 13

58. A Top Down view of BioPAX: properties
• Datatype properties
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque-Tecnológico de Bizkaia - Nov. 7th 2012
Bilbao Nov. 7th 2012
martedì 22 ottobre 13

59. BioPAX representation details: entities
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

60. BioPAX representation details: pathways
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

61. BioPAX representation details: interactions
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

62. BioPAX representation details: genetic interactions
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

63. BioPAX representation details: control
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

64. BioPAX representation details: template reactions
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

65. BioPAX: Biological Pathway Exchange (language)
•Why ?
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

66. Why ? Data availability
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

67. Why ? Data availability
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

68. Why ? Simplified Access to Data
• Pathway represented with a common Syntax and “Semantics”
• Tools: SPARQL (RDF) or PaxTools (Object Model)
• Derivate information (e.g.: SIF files)
• Still not for end-users...
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

69. Why ? Simplified Access to Data (SIF detail)
• When possible!
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

70. Why ? BioPAX and the Systems Biology
Information ecosystem
Database Exchange
Formats
Simulation Model
Exchange Formats
BioPAX
Genetic
Interactions
PSI
Interaction Networks
Molecular
Pro:Pro
Non-molecular
TF:Gene
SBML,
CellML
High Detail
Genetic
Rate
Formulas
Molecular Interactions
Pro:Pro
All:All
Small Molecules
Low Detail
High Detail
• Harmony
• Combine
Regulatory Pathways
Low Detail
• Co-operation:
Biochemical
Reactions
Metabolic Pathways
Low Detail
High Detail
Gene ontology ?
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

71. Why ? Integration and computability,
the meaning of the BioPAX ontology
• The BioPAX ontology describes the structure of pathways.
• While the object of the ontology are “pathways” the way the ontology is
designed is heavily influenced by the conceptualization of pathways as
“information artifacts”.
• While making use of OWL constructs, BioPAX offers little scope to
classification (and consistency).
• The design of BioPAX reflects an hybrid approach between ontologies and
Object Oriented modeling.
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

72. Why ? BioPAX and Bio-Ontologies
A comparison with BFO
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

73. Why ? BioPAX and Bio-Ontologies
A comparison with BFO
• Which is the conceptualization
behind the top level of BioPAX ?
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

74. Why ? BioPAX and Bio-Ontologies
Not a pure ontology
• Property definition in
OBO
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

75. Why ? BioPAX and Bio-Ontologies
Not a pure ontology
• Property description
in BioPAX
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

76. Why ? BioPAX and Bio-Ontologies
Not a pure ontology
• BioPAX Overloading
Knowledge base:
efficiency
OWL
Data Model
PaxTools
RDF
Ontology
XML
Syntax, validation rules
Exchange language
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

77. Why ? BioPAX limitations
• Different
representations:
• Generalization ?
• Water ?
• Pathway
reconciliation is
still in research
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

78. Why ?
• BioPAX provides a large amount of data represented in a coherent syntax
• The semantics of the BioPAX ontology, while imperfect, represents a
consensus among pathway providers
• BioPAX provides a knowledge bases to which different conceptualizations
can be applied
• BioPAX is a bridge between standards (language + community)
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13

79. BioPAX: next
• http://biopax.org
• biopax-discuss@googlegroups.com
• http://www.biopax.org/release/biopax-level3.owl
• http://www.biopax.org/release/biopax-level3-documentation.pdf
• The BioPAX community standard for pathway data sharing
Emek Demir, Michael P Cary, Suzanne Paley, Ken Fukuda, Christian Lemer, Imre Vastrik, Guanming Wu, Peter D'Eustachio, Carl Schaefer, Joanne Luciano, Frank
Schacherer, Irma Martinez-Flores, Zhenjun Hu, Veronica Jimenez-Jacinto, Geeta Joshi-Tope, Kumaran Kandasamy, Alejandra C Lopez-Fuentes, Huaiyu Mi, Elgar Pichler,
Igor Rodchenkov, Andrea Splendiani, Sasha Tkachev, Jeremy Zucker, Gopal Gopinath, Harsha Rajasimha et al.
Nature Biotechnology 28, 935–942 (2010)
Andrea Splendiani
BioPAX (an introduction) - Bioledge Workshop - Parque Tecnológico de Bizkaia - Nov. 7th 2012
martedì 22 ottobre 13