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The Translational Medicine Ontology: driving personalized medicine by bridging the gap from bedside to bench,[object Object],1,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object],Michel Dumontier,[object Object],on behalf of the HCLS TMO Subgroup,[object Object],Carleton University, Ottawa, Canada,[object Object]
2,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object]
HCLS TMO subgroup,[object Object],BosseAndersson, AstraZeneca, Lund, Sweden,[object Object],Colin Batchelor, Royal Society of Chemistry, Cambridge, UK,[object Object],Christine Denney, Eli Lilly, Indianapolis, IN, USA,[object Object],Christopher Domarew, Warrington Hospital, Warrington, UK,[object Object],AnjaJentzsch, FreieUniversitat, Berlin, Germany ,[object Object],Joanne Luciano, Predictive Medicine Inc., Belmont, MA, USA,[object Object],Elgar Pichler, W3C HCLSIG,[object Object],Eric Prud'hommeaux, W3C, Cambridge, MA, USA,[object Object],Patricia L. Whetzel, Stanford University, Stanford, CA, USA,[object Object],Olivier Bodenreider, National Library of Medicine, Bethesda, MD, USA,[object Object],Tim Clark, Harvard Medical School, Cambridge, MA, USA ,,[object Object],Lee Harland, Pfizer, Sandwich, UK ,[object Object],VipulKashyap, Cigna, Hartford, CT, USA ,[object Object],Peter Kos, Harvard Medical School, Cambridge, MA, USA ,[object Object],Julia Kozlovsky, AstraZeneca, Waltham, MA, USA,[object Object],James McGurk, Daiichi Sankyo, NJ, USA,[object Object],ChimezieOgbuji Cleveland Clinic, Cleveland,OH, USA,[object Object],Matthias Samwald, Digital Enterprise Research Institute, Galway, Ireland ,[object Object],Lynn Schriml, University of Maryland, Institute for Genome Sciences ,[object Object],Peter J. Tonellato, Harvard Medical School, Cambridge, MA, USA,[object Object],Jun Zhao, University of Oxford, Oxford, UK.,[object Object],Susie StephensJohnson & Johnson Pharmaceutical Research & Development L.L.C., Radnor, PA, USA.,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object],3,[object Object]
Goals of the W3C HCLSIG,[object Object],Advance the state of the art in knowledge discovery for health care and the life sciences,[object Object],Investigate approaches to facilitate the integration of patient care, clinical research and basic life science research,[object Object],Provide effective demonstrations of using Semantic Web technologies for knowledge representation, data integration, data visualization and question answering ,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object],4,[object Object]
Personalized Medicine,[object Object],The ability to offer ,[object Object],The Right Drug,[object Object],To The Right Patient,[object Object],For The Right Disease,[object Object],At The Right Time,[object Object],With The Right Dosage,[object Object],	Genetic and metabolic data will allow drugs to be tailored to patient subgroups,[object Object],5,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object]
	“If it were not for the great variability among individuals, medicine might as well be a science and not an art”,[object Object],		Sir William Osler, 1892,[object Object],6,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object]
7,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object]
8,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object]
9,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object]
The Semantic Web,[object Object], is the new global web of knowledge,[object Object],10,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object],It is about standards for publishing, sharing and querying ,[object Object],knowledge drawn from diverse sources,[object Object],It makes possible the answering,[object Object],sophisticated questions using,[object Object], background knowledge,[object Object]
A growing web of linked data,[object Object],11,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object]
Bio-ontologies 2010:July 9, 2010,[object Object],How do we query across these linked data?,[object Object],12,[object Object]
Formal Ontology as a Strategy,[object Object],13,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object]
Problem Statement,[object Object],Growing number of biomedical terminologies,[object Object],Over 200 listed at NCBO bioportal,[object Object],Ontologies are a formal specification of a conceptualization,[object Object],Not all are well formulated, nor properly formalized,[object Object],OBO Foundry to create a reference set of ontologies, but the task is enormous, until then, we need working solutions,[object Object],Increasing amounts of linked data,[object Object],Conceptualization is haphazard ,[object Object],not formulated using formal ontologies,[object Object],Relations and types are not grounded to shared conceptualization. ,[object Object],ontologies applied to linked data will be useful to integrate and provide support for queries,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object],14,[object Object]
TMO Approach,[object Object],Undertake extensive user-focused requirements,[object Object],Identify key entities and establish their relations,[object Object],Extend the conceptualization as specified by a  foundational ontology,[object Object],Map linked data types to ontology types,[object Object],Develop knowledge base containing ontology + mappings + data,[object Object],Demonstrate query answering over TMO KB,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object],15,[object Object]
Survey reveals diverse needs and interests,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object],16,[object Object]
Preparation,[object Object],Generate plausible questions of interest,[object Object],Generate scenerios,[object Object],patient centric,[object Object],research centric,[object Object],chemoinformatics / drug discovery,[object Object],pharmacogenomics,[object Object],animal models,[object Object],integrative informatics,[object Object],drug therapy development,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object],17,[object Object]
Ontology,[object Object],[object Object],Distinction among different kinds of material entities,[object Object],molecular entities vs chemical substances,[object Object],active ingredients vs pharmaceutical formulations,[object Object],Distinction among different kinds of informational entities,[object Object],medical,[object Object],medical history (a list of events & bodily features), diagnostic results,[object Object],drug,[object Object],dosage (specification), toxicity (reports), treatment safety (guidelines),[object Object],Bio-ontologies 2010:July 9, 2010,[object Object],18,[object Object]
Bio-ontologies 2010:July 9, 2010,[object Object],19,[object Object],223 class mappings,[object Object], from 60 TMO classes to 201 target classes over 40 ontologies,[object Object]
Data,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object],20,[object Object]
Linking Open Drug Data (LODD),[object Object],Bio-ontologies 2010:July 9, 2010,[object Object],21,[object Object]
focus: Alzheimer’s Disease (AD),[object Object],Incurable, degenerative, and terminal disease with few therapeutic options. ,[object Object],Influenced by a range of genetic, environmental and other factors. ,[object Object],Identification of prognostic biomarkers would significantly impact and guide the diagnosis, prescription, and development of therapeutic agents would significantly impact future practice. ,[object Object],Efficient aggregation of relevant information to help understand the pathology would benefit researchers, clinicians, and patients and would also facilitate the development of target compounds to reduce or even prevent the burden of the disease.,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object],22,[object Object]
formalizing the Dubois AD diagnostic criteria,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object],23,[object Object],# the panel is a textual entity,[object Object],dubois:panel2 a iao:IAO_0000300 .,[object Object],dubois:panel2 rdfs:label "Alzheimer Disease diagnostic criteria as reported in panel 2 of dubois et al - pubmed:17616482  [dubois:panel2]".,[object Object],# the panel is about alzheimer disease,[object Object],dubois:panel2 iao:is_about diseasome:74.,[object Object],# the panel is from the article,[object Object],dubois:panel2 ro:part_of <http://bio2rdf.org/pubmed:17616482>.,[object Object],# the panel is about diagnostic criterion,[object Object],dubois:panel2 iao:is_about tmo:TMO_0068.,[object Object],#inclusion criterion,[object Object],dubois:10 rdfs:label "Proven AD autosomal dominant mutation within the immediate family [dubois:10]" ;,[object Object], a tmo:TMO_0069;,[object Object],ro:part_of dubois:panel2;,[object Object],iao:is_about diseasome:74.,[object Object],# exclusion criterion,[object Object],dubois:16 rdfs:label "Major depression [dubois:16]" ;,[object Object], a tmo:TMO_0070;,[object Object],ro:part_of dubois:panel2;,[object Object],iao:is_about diseasome:74.,[object Object]
Queries,[object Object],Clinic,[object Object],Have any AD patients been treated for other neurological conditions ,[object Object],Patient 2 was found to suffer from AD and depression.,[object Object],Clinical Trial,[object Object],Since my patient is suffering from drug-induced side effects for AD treatment, identify an AD clinical trial with a different mechanism of action (MOA),[object Object],Of the 438 drugs linked to AD trials, only 58 are in active trials and only 2 (Doxorubicin and IL-2) have a documented MOA. 78 AD-associated drugs have an established MOA.,[object Object],Research,[object Object],Which existing marketed drugs might potentially be re-purposed for AD because they are known to modulate genes that are implicated in the disease?,[object Object],57 compounds or classes of compounds that are used to treat 45 diseases, including AD, hyper/hypotension, diabetes and obesity,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object],24,[object Object],http://esw.w3.org/topic/HCLSIG/PharmaOntology/Queries,[object Object]
Future Directions,[object Object],Enhancement of ontology to increase coverage,[object Object],Increased formalization of patient records so as to facilitate patient recruitment,[object Object],Formalization of pathway diagrams and the aggregate set of processes they specify,[object Object],Refactoring of linked data,[object Object],more explicit representation of quantities/values,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object],25,[object Object]
The Translational Medicine Ontology,[object Object],Provides a global schema for the integration of linked data sets,[object Object],Establishes accurate mappings to relevant ontologies,[object Object],Demonstrative knowledge base focused around AD,[object Object],Bio-ontologies 2010:July 9, 2010,[object Object],26,[object Object]

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The Translational Medicine Ontology: Driving personalized medicine by bridging the gap from bedside to benchside

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Notes de l'éditeur

  1. to be posted on slideshre, license fordistribution