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


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The Translational Medicine Ontology provides terminology that bridges diverse areas of translational medicine including hypothesis management, discovery research, drug development and formulation, clinical research, and clinical practice. Designed primarily from use cases, the ontology consists of essential terms that are mapped to other ontologies. It serves as a global schema for data integration while simultaneously facilitating the formulation of complex queries across heterogeneous sources. We demonstrate the utility of the ontology through question answering over a prototype knowledge base composed of sample patient data integrated with linked open data. This work forms a basis for the development of a computational platform for managing information relevant to personalized medicine.

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

  1. 1. The Translational Medicine Ontology: driving personalized medicine by bridging the gap from bedside to bench<br />1<br />Bio-ontologies 2010:July 9, 2010<br />Michel Dumontier<br />on behalf of the HCLS TMO Subgroup<br />Carleton University, Ottawa, Canada<br />
  2. 2. 2<br />Bio-ontologies 2010:July 9, 2010<br />
  3. 3. HCLS TMO subgroup<br />BosseAndersson, AstraZeneca, Lund, Sweden<br />Colin Batchelor, Royal Society of Chemistry, Cambridge, UK<br />Christine Denney, Eli Lilly, Indianapolis, IN, USA<br />Christopher Domarew, Warrington Hospital, Warrington, UK<br />AnjaJentzsch, FreieUniversitat, Berlin, Germany <br />Joanne Luciano, Predictive Medicine Inc., Belmont, MA, USA<br />Elgar Pichler, W3C HCLSIG<br />Eric Prud'hommeaux, W3C, Cambridge, MA, USA<br />Patricia L. Whetzel, Stanford University, Stanford, CA, USA<br />Olivier Bodenreider, National Library of Medicine, Bethesda, MD, USA<br />Tim Clark, Harvard Medical School, Cambridge, MA, USA ,<br />Lee Harland, Pfizer, Sandwich, UK <br />VipulKashyap, Cigna, Hartford, CT, USA <br />Peter Kos, Harvard Medical School, Cambridge, MA, USA <br />Julia Kozlovsky, AstraZeneca, Waltham, MA, USA<br />James McGurk, Daiichi Sankyo, NJ, USA<br />ChimezieOgbuji Cleveland Clinic, Cleveland,OH, USA<br />Matthias Samwald, Digital Enterprise Research Institute, Galway, Ireland <br />Lynn Schriml, University of Maryland, Institute for Genome Sciences <br />Peter J. Tonellato, Harvard Medical School, Cambridge, MA, USA<br />Jun Zhao, University of Oxford, Oxford, UK.<br />Susie StephensJohnson & Johnson Pharmaceutical Research & Development L.L.C., Radnor, PA, USA.<br />Bio-ontologies 2010:July 9, 2010<br />3<br />
  4. 4. Goals of the W3C HCLSIG<br />Advance the state of the art in knowledge discovery for health care and the life sciences<br />Investigate approaches to facilitate the integration of patient care, clinical research and basic life science research<br />Provide effective demonstrations of using Semantic Web technologies for knowledge representation, data integration, data visualization and question answering <br />Bio-ontologies 2010:July 9, 2010<br />4<br />
  5. 5. Personalized Medicine<br />The ability to offer <br />The Right Drug<br />To The Right Patient<br />For The Right Disease<br />At The Right Time<br />With The Right Dosage<br /> Genetic and metabolic data will allow drugs to be tailored to patient subgroups<br />5<br />Bio-ontologies 2010:July 9, 2010<br />
  6. 6. “If it were not for the great variability among individuals, medicine might as well be a science and not an art”<br /> Sir William Osler, 1892<br />6<br />Bio-ontologies 2010:July 9, 2010<br />
  7. 7. 7<br />Bio-ontologies 2010:July 9, 2010<br />
  8. 8. 8<br />Bio-ontologies 2010:July 9, 2010<br />
  9. 9. 9<br />Bio-ontologies 2010:July 9, 2010<br />
  10. 10. The Semantic Web<br /> is the new global web of knowledge<br />10<br />Bio-ontologies 2010:July 9, 2010<br />It is about standards for publishing, sharing and querying <br />knowledge drawn from diverse sources<br />It makes possible the answering<br />sophisticated questions using<br /> background knowledge<br />
  11. 11. A growing web of linked data<br />11<br />Bio-ontologies 2010:July 9, 2010<br />
  12. 12. Bio-ontologies 2010:July 9, 2010<br />How do we query across these linked data?<br />12<br />
  13. 13. Formal Ontology as a Strategy<br />13<br />Bio-ontologies 2010:July 9, 2010<br />
  14. 14. Problem Statement<br />Growing number of biomedical terminologies<br />Over 200 listed at NCBO bioportal<br />Ontologies are a formal specification of a conceptualization<br />Not all are well formulated, nor properly formalized<br />OBO Foundry to create a reference set of ontologies, but the task is enormous, until then, we need working solutions<br />Increasing amounts of linked data<br />Conceptualization is haphazard <br />not formulated using formal ontologies<br />Relations and types are not grounded to shared conceptualization. <br />ontologies applied to linked data will be useful to integrate and provide support for queries<br />Bio-ontologies 2010:July 9, 2010<br />14<br />
  15. 15. TMO Approach<br />Undertake extensive user-focused requirements<br />Identify key entities and establish their relations<br />Extend the conceptualization as specified by a foundational ontology<br />Map linked data types to ontology types<br />Develop knowledge base containing ontology + mappings + data<br />Demonstrate query answering over TMO KB<br />Bio-ontologies 2010:July 9, 2010<br />15<br />
  16. 16. Survey reveals diverse needs and interests<br />Bio-ontologies 2010:July 9, 2010<br />16<br />
  17. 17. Preparation<br />Generate plausible questions of interest<br />Generate scenerios<br />patient centric<br />research centric<br />chemoinformatics / drug discovery<br />pharmacogenomics<br />animal models<br />integrative informatics<br />drug therapy development<br />Bio-ontologies 2010:July 9, 2010<br />17<br />
  18. 18. Ontology<br /><ul><li>75 classes out of an initial 90 types spanning material entities, processes, roles, informational entities</li></ul>Distinction among different kinds of material entities<br />molecular entities vs chemical substances<br />active ingredients vs pharmaceutical formulations<br />Distinction among different kinds of informational entities<br />medical<br />medical history (a list of events & bodily features), diagnostic results<br />drug<br />dosage (specification), toxicity (reports), treatment safety (guidelines)<br />Bio-ontologies 2010:July 9, 2010<br />18<br />
  19. 19. Bio-ontologies 2010:July 9, 2010<br />19<br />223 class mappings<br /> from 60 TMO classes to 201 target classes over 40 ontologies<br />
  20. 20. Data<br />Bio-ontologies 2010:July 9, 2010<br />20<br />
  21. 21. Linking Open Drug Data (LODD)<br />Bio-ontologies 2010:July 9, 2010<br />21<br />
  22. 22. focus: Alzheimer’s Disease (AD)<br />Incurable, degenerative, and terminal disease with few therapeutic options. <br />Influenced by a range of genetic, environmental and other factors. <br />Identification of prognostic biomarkers would significantly impact and guide the diagnosis, prescription, and development of therapeutic agents would significantly impact future practice. <br />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.<br />Bio-ontologies 2010:July 9, 2010<br />22<br />
  23. 23. formalizing the Dubois AD diagnostic criteria<br />Bio-ontologies 2010:July 9, 2010<br />23<br /># the panel is a textual entity<br />dubois:panel2 a iao:IAO_0000300 .<br />dubois:panel2 rdfs:label "Alzheimer Disease diagnostic criteria as reported in panel 2 of dubois et al - pubmed:17616482 [dubois:panel2]".<br /># the panel is about alzheimer disease<br />dubois:panel2 iao:is_about diseasome:74.<br /># the panel is from the article<br />dubois:panel2 ro:part_of <>.<br /># the panel is about diagnostic criterion<br />dubois:panel2 iao:is_about tmo:TMO_0068.<br />#inclusion criterion<br />dubois:10 rdfs:label "Proven AD autosomal dominant mutation within the immediate family [dubois:10]" ;<br /> a tmo:TMO_0069;<br />ro:part_of dubois:panel2;<br />iao:is_about diseasome:74.<br /># exclusion criterion<br />dubois:16 rdfs:label "Major depression [dubois:16]" ;<br /> a tmo:TMO_0070;<br />ro:part_of dubois:panel2;<br />iao:is_about diseasome:74.<br />
  24. 24. Queries<br />Clinic<br />Have any AD patients been treated for other neurological conditions <br />Patient 2 was found to suffer from AD and depression.<br />Clinical Trial<br />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)<br />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.<br />Research<br />Which existing marketed drugs might potentially be re-purposed for AD because they are known to modulate genes that are implicated in the disease?<br />57 compounds or classes of compounds that are used to treat 45 diseases, including AD, hyper/hypotension, diabetes and obesity<br />Bio-ontologies 2010:July 9, 2010<br />24<br /><br />
  25. 25. Future Directions<br />Enhancement of ontology to increase coverage<br />Increased formalization of patient records so as to facilitate patient recruitment<br />Formalization of pathway diagrams and the aggregate set of processes they specify<br />Refactoring of linked data<br />more explicit representation of quantities/values<br />Bio-ontologies 2010:July 9, 2010<br />25<br />
  26. 26. The Translational Medicine Ontology<br />Provides a global schema for the integration of linked data sets<br />Establishes accurate mappings to relevant ontologies<br />Demonstrative knowledge base focused around AD<br />Bio-ontologies 2010:July 9, 2010<br />26<br />
  27. 27. Bio-ontologies 2010:July 9, 2010<br />27<br />Acknowledgements<br />