This presentation was given as part of the University of Ottawa TAMALE group seminar series: http://tamale.uottawa.ca

1. Evaluating scientific Hypotheses using semantic web technologies Alison Callahan TAMALE Seminar November 8 2010

2. Why the semantic web? PLAIN TEXT What you see: “The weather today, November 8, will be cloudy with a high of 7°C” What your computer sees: akfalksjdfoaohwoiehroe XML What you see: <weather> <date> <month>November</month> <day>8</day> <year>2010</year> </date> <temperature> <value>7</value> <unit>Celcius</unit> </temperature> <conditions>cloudy</conditions> </weather> What your computer sees: <weather> <date> <month>November</month> <day>8</day> <year>2010</year> </date> <temperature> <value>5</value> <unit>Celcius</unit> </temperature> <condi>Flurries</condi> </weather>

4. Source: http://www.webcitation.org/5u4OJ6rYe

5. RDF Resource Description Framework: A W3C standard for representing resources and the relationships between them, and for data exchange on the WWW Alison reading likes subject predicate object http://people.com#Alisonhttp://feelings.com#likes http://activities.com#reading <rdf:RDF> <rdf:Descriptionrdf:about="http://people.com#Alison"> <likesxmlns="http://feelings.com#" rdf:resource="http://activities.com#reading"/> </rdf:Description> </rdf:RDF>

6. educational institution foaf:person rdf:type Carleton University rdf:type works at reading Alison likes has brother Chris rdf:type foaf:person

7. Querying RDF using SPARQL SPARQL = SPARQL Protocol and RDF Query Language select ?s where { ?s rdf:typefoaf:Person . } http://people.com#Alison http://people.com#Christopher

8. OWL: The web ontology language OWL allows the representation of ontology concepts in a machine understandable manner MotherWomanhasChildPerson

9. Biological SCIENCES and the semantic web http://bio2rdf.org http://bioportal.bioontology.org

10. HYQUE Hypothesis-based query and evaluation tool http://semanticscience.org/projects/hyque

11. Source :http://xkcd.com/242/

12. Source: http://kentsimmons.uwinnipeg.ca/cm1504/introscience.htm

13. Finding evidence to support/refute a hypothesis is becoming increasingly difficult Source: http://upload.wikimedia.org/wikipedia/commons/2/26/EnwikipediaArt.PNG

15. minimum event-based vocabulary

16. uses consistency checking to evaluate hypotheses

17. constraints

18. rules

19. compares hypotheses using neighborhood functions

20. incremental hypothesis improvement[1] Racunas S. A., Shah N. H., Albert I. and Fedoroff N. V. (2004). HyBrow: A prototype system for computer-aided hypothesis evaluation. Bioinformatics 20(S. 1): i1-i8.

22. hard coded Perl rules

23. challenging to apply to a new domain

25. Uses RDF/SPARQL/OWL

26. Background knowledge encoded as OWL ontologies

27. Queries Bio2RDF’s dedicated SPARQL endpoints

28. Context-specific rules that consider experimental conditions

29. HyQueconsumes and producesRDFPaper: Callahan, A., M. Dumontier & N. Shah. 2010. HyQue: Evaluating hypotheses using Semantic Web technologies. Bio-ontologies SIG, ISMB’10, Boston MA. On the web: http://semanticscience.org/projects/hyque

31. SGD data in Bio2RDF

32. Template event-based SPARQL queries

34. HyQue hypotheses are composed of propositions connected using logical operators (AND, OR…)HyQuehypothesis ‘proposition’ that ‘has part’ some ‘hypothesis part’ Hypothesis part ‘proposition’ that ‘has component’ some ‘event’

35. HyQue events Events are composed of conditional assertions on a relation between ‘actor’ and ‘target’ induces(actor, target, context, location) For decidable logic (OWL), an n-ary object is used Event agent_aactor agent_btarget perturbation_contextcontext physical_locationlocation

36. HyQue Data … but first, a biology primer!

38. How are these processes regulated? Source: http://www.webcitation.org/5u4OelqJO

39. Where do OUR CELLS get energy?

41. permease – gal2p – transports galactose into cells

42. galactokinase – gal1p

43. uridylyltransferase – gal7p

44. epimerase – gal10p

45. phosphoglucomutase –gal5p

46. Regulation – whether the pathway is on or off

47. gal3p

48. gal4p

49. gal80penzymes that use galactose

50. Source: Ostergaardet al. (2000). Nature Biotechnology 18: 1283 - 1286

51. HyQue data Experimentally determined interactions between the GAL proteins Properties of the genes that encode these proteins (SGD) Literature-based evidence (citations) Knowledge about cellular locations and events (GO) Types of evidence supporting these interactions (ECO)

52. How does HyQue work?

53. Individual events parsed from input hypothesis RDF hypothesis :h a hyque:Hypothesis ; a hyque:AND ; hyque:hasPart :p1 ; hyque:hasPart :p2 ; hyque:hasPart :p3 . :p1 a hyque:AND ; hyque:hasComponent :e1 ; hyque:hasComponent :e2 . :e1 a <http://bio2rdf.org/go:0006810> ; hybrow:is_negated “0”^^xsd:boolean ; hybrow:agent_a <http://bio2rdf.org/sgd:Gal2p> ; hybrow:agent_b <http://bio2rdf.org/chebi:28260> . :e2 a <http://bio2rdf.org/go:0005488> ; hybrow:is_negated “0”^^xsd:boolean ; hybrow:agent_a <http://bio2rdf.org/sgd:Gal3p> ; hybrow:agent_b <http://bio2rdf.org/sgd:Gal80p> . has part hypothesis part 1 has component gal2p transports galactose gal3p binds to gal80p

54. Template SPARQL queries completed based on event properties :e1 a go:0006810 ; hybrow:is_negated "0" ; hybrow:agent_asgd:Gal2p ; hybrow:agent_bchebi:28260 . construct { … } where { … ?event hybrow:is_negated ?negated . ?event hybrow:physical_operator ?physical_operator . ?event hybrow:agent_a <http://bio2rdf.org/sgd:Gal2p> . … ?event hybrow:agent_b <http://bio2rdf.org/chebi:28260> . ?actor semsci:isLocatedIn ?actor_gp_id_location . ?actor_gp_id_locationrdf:type ?actor_location_type . ?actor semsci:hasFunction ?actor_gp_id_function . ?actor_gp_id_functionrdf:type ?actor_function . … }

55. SPARQL query results retrieved hybrow_data:2c1789a3019fd2fe9843d507824fc591 rdf:type <http://bio2rdf.org/go:0044092> . hybrow:is_negated "0" . hybrow:agent_a sgd:Gal3p ; hybrow:agent_b sgd:Gal80p ; hybrow:actor_type <http://bio2rdf.org/chebi:36080> ; hybrow:target_type <http://bio2rdf.org/chebi:36080> ; hybrow:physical_context <http://bio2rdf.org/go:0005634> ; hybrow:physical_operator <http://bio2rdf.org/go:0005488> . hybrow_data:b09f7cc043201b47610c874499448a23 rdf:type <http://bio2rdf.org/go:0005488> ; hybrow:is_negated "0" ; hybrow:agent_a sgd:Gal3p ; hybrow:agent_b sgd:Gal80p ; hybrow:actor_type <http://bio2rdf.org/chebi:36080> ; hybrow:target_type <http://bio2rdf.org/chebi:36080> ; hybrow:physical_context <http://bio2rdf.org/go:0005634> ; hybrow:physical_operator <http://bio2rdf.org/go:0005488> .

56. Query results evaluated based on rule sets ‘binding’ rule: Is event negated? If yes, subtract 2 Is physical operator ‘binding’? If yes, add 1; if no, subtract 1 Is actor of type ‘protein’ or ‘small molecule’? If yes, add 1; if of type ‘gene’, subtract 1 Is target of type ‘protein’ or ‘small molecule’? If yes, add 1; if of type ‘gene’, subtract 1 Does actor have known ‘binding’ function? If yes, add 1 GO:0005488 CHEBI:36080 SO:0000236

57. Result scores based on operators between events Final score = e1 score + e2 score + e3 score + e4 score Final score = maximum of e5, e6 or e7 scores :p1 a hyque:AND ; hyque:hasComponent :e1 ; hyque:hasComponent :e2 ; hyque:hasComponent :e3 ; hyque:hasComponent :e4 . :p2 a hyque:OR ; hyque:hasComponent :e5 ; hyque:hasComponent :e6 ; hyque:hasComponent :e7 .

58. Hypothesis evaluation RDF generated

63. Questions?