1) The document discusses challenges in curing complex medical disorders and proposes that semantic annotation, hypothesis management, and nanopublications can help address these challenges by enabling improved information sharing and integration across research communities. 2) It describes various technologies and frameworks like the Annotation Ontology, SWAN Annotation Framework, and nanopublications that can help researchers semantically annotate documents, manage hypotheses, and publish and share interpretations. 3) International collaborations between researchers and informaticians are seen as important to building the information ecosystem needed to make progress on curing complex diseases.

1. Tim Clark Harvard Medical School & Massachusetts General Hospital April 12, 2011 Copyright 2010 Massachusetts General Hospital. All rights reserved.

4. create hypothesis design experiment run experiment collect data interpret data share interpretations synthesize knowledge

5. MCI progressors non progressors PET imaging of PIB (radiolabelled compound binds amyloid beta A4 protein) MRI imaging of brain structure showing loss of hippocampal volume Brain. 2010 Nov;133(Pt 11):3336-3348 . = 218 subjects +

6. dopaminergic pathway α-synuclein, β-amlyoid α-synuclein, Tau chr 16p11.2 CNV chr 16p11.2 CNV CRF, glutaminergic system, dopamine, amygdala … Alzheimer Disease Parkinson ’s Disease Schizophrenia Autism Bipolar Disorder Drug Addiction Huntington ’s Disease ALS Depression SIRT2

8. 1667 2010 Printing Press Web

9. We scientists do not attend professional meetings to present our findings ex cathedra, but in order to argue. John Polanyi, FRS, Nobel Laureate University of Manchester

13. Genes Proteins Biological Processes Chemical Compounds Antibodies Cells Brain anatomy …

15. Text Shared metadata

16. 2) Automatic annotation Dr. Paolo Ciccarese – Oct 8, 2010

17. Dr. Paolo Ciccarese – Oct 8, 2010

25. Dr. Paolo Ciccarese – Oct 8, 2010

26. Dr. Paolo Ciccarese – Oct 8, 2010

27. Dr. Paolo Ciccarese – Oct 8, 2010

28. With thanks to Barend Mons and Paul Groth… Mons / Groth model of a nanopublication Cognitive Deficits (S) BACE1 (O) Relate to (p) provenance context

29. swande:Claim <http://tinyurl.com/4h2am3a> Intramembranous Aβ behaves as chaperones of other membrane proteins rdf:type dct:title G1 <http://example.info/person/1> pav:authoredBy Vincent Marchesi foaf:name foaf:Person rdf:type pav: http://purl.org/pav/provenance/2.0/ foaf: http://xmlns.com/foaf/0.1/ G2

30. swande:Claim <http://tinyurl.com/4h2am3a> Intramembranous Aβ behaves as chaperones of other membrane proteins rdf:type dct:title G1 <http://example.info/person/1> pav:authoredBy G2 <http://example.info/person/0> pav:curatedBy G4 Gwen Wong foaf:name foaf:Person rdf:type

31. swande:Claim <http://tinyurl.com/4h2am3a> Intramembranous Aβ behaves as chaperones of other membrane proteins rdf:type dct:title G1 <http://example.info/person/1> pav:contributedBy <http://example.info/citation/1> swanrel:referencesAsSupportiveEvidence G5 G6

32. G8 <http://example.info/alzswan:statement_f3556dcfc331d9b9af9d5c0cfc570ba6_event_1> <http://bio2rdf.org/go:0051087> rdf:type Event of type GO &quot;chaperone binding&quot; rdfs:label <prefix:actor_1> <prefix:target_1> <prefix:location_1> <http://bio2rdf.org/chebi:53002> <http://bio2rdf.org/mesh:D008565> <http://bio2rdf.org/go:0005886> rdf:type rdf:type rdf:type rdfs:label “Beta amyloid” rdfs:label “Membrane protein” rdfs:label “Plasma membrane” With many thanks to Nigam Shah, Stanford University

33. Hyque triples G8 <http://example.info/person/2> pav:contributedBy Nigam Shah foaf:name foaf:Person rdf:type G9

34. swande:Claim <http://tinyurl.com/4h2am3a> Intramembranous Aβ behaves as chaperones of other membrane proteins rdf:type dct:title G1 Hyque triples G8 swanrel:derivedFrom

38. Information ecosystem