The document discusses the evaluation of scientific hypotheses using semantic web technologies, focusing on tools like HyQue and Hybrow that leverage RDF, SPARQL, and ontology languages for hypothesis assessment and data integration. It emphasizes the challenges in finding evidence to support or refute hypotheses and introduces methods for parsing input hypotheses and evaluating them through constructed queries. The author highlights the importance of machine-readable data and ontology representations in advancing scientific inquiry and hypothesis testing.

1. Evaluating scientific Hypotheses using semantic web technologiesAlison CallahanTAMALE SeminarNovember 8 2010

2. Why the semantic web?PLAIN TEXTWhat you see: “The weather today, November 8, will be cloudy with a high of 7°C”What your computer sees: akfalksjdfoaohwoiehroeXMLWhat 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. RDFResource Description Framework: A W3C standard for representing resources and the relationships between them, and for data exchange on the WWWAlisonreadinglikes 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 institutionfoaf:personrdf:typeCarleton Universityrdf:typeworks atreadingAlisonlikeshas brotherChrisrdf:typefoaf:person

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

8. OWL: The web ontology languageOWL allows the representation of ontology concepts in a machine understandable mannerMotherWomanhasChildPerson

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

10. HYQUEHypothesis-based query and evaluation toolhttp://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 difficultSource: http://upload.wikimedia.org/wikipedia/commons/2/26/EnwikipediaArt.PNG

14. HyBrowComputationally augmented method for hypothesis evaluationdeveloped by Racunas et al. [1]

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.

21. HyBrowsmall, manually generated knowledge

22. hard coded Perl rules

23. challenging to apply to a new domain

24. needs access to a greater KBHyBrow HyQueHypothesis query and evaluation system

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

30. HyQue is composed of …HyQue hypothesis ontologyDescribes generic input hypothesis and output hypothesis evaluation classesUses upper level classes e.g. ‘proposition’, ‘measurement value’, ‘event’ HyBrow SPARQL endpoint

31. SGD data in Bio2RDF

32. Template event-based SPARQL queries

33. GO, SO, ChEBI, ECO ontologiesA HyQue hypothesis is a collection of propositionsproposition: “a statement expressing something true or false”

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 eventsEvents 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 usedEventagent_aactoragent_btargetperturbation_contextcontextphysical_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?

40. HyQue data: The gal gene network IN YEASTGenes that encode proteins that transport and metabolize galactose

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 dataExperimentally determined interactions between the GAL proteinsProperties 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 RDFhypothesis: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 parthypothesis part 1has componentgal2p transports galactosegal3p 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 retrievedhybrow_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 2Is physical operator ‘binding’?If yes, add 1; if no, subtract 1Is actor of type ‘protein’ or ‘small molecule’?If yes, add 1; if of type ‘gene’, subtract 1Is target of type ‘protein’ or ‘small molecule’? If yes, add 1; if of type ‘gene’, subtract 1Does actor have known ‘binding’ function? If yes, add 1 GO:0005488CHEBI:36080SO:0000236

57. Result scores based on operators between eventsFinal score = e1 score + e2 score + e3 score + e4 scoreFinal 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

61. HyQue as a SADI serviceSADI – Semantic Automated Discovery and IntegrationHyQueSADI ontology to describe input and output of service

62. Users can post a hypothesis in RDF and receive the hypothesis evaluation in RDFACKNOWLEDGEMENTSMy supervisor: Dr. Michel DumontierProject collaborator: Dr. Nigam Shah http://stanford.edu/~nigamThe Dumontier Lab: http://dumontierlab.comFunding: NSERC to MD

63. Questions?