BFO-aligned Ontologies for Clinical and Translational Research: OGMS, IDO, and VO (Orlando Presentation, 2/8/2013) Yongqun “Oliver” He University of Michigan Medical School Ann Arbor, MI 48109

BFO and OBO Foundry Principles BFO: Basic Formal Ontology BFO has been used a top level ontology for many ontologies associated with clinical and translational research Examples: OGMS, IDO, VO, OBI, OAE All OBO foundry library ontologies follow OBO Foundry principles, e.g., openness, collaboration, and use of a common shared syntax

OGMS: Ontology of General Medical Science An ontology of the major types of entities involved in a clinical encounter. –An upper ontology for clinical medicine –A mid-level ontology with respect to BFO Includes ~100 general terms By: –Albert Goldfain –Richard Scheuermann –Barry Smith, … code.google.com /p/ogms/

Wide OGMS Applications Ontologies using OGMS: IDO DO SDO AERO OAE VSO OMRSE VO... Courtesy: figure kindly provided by Albert Goldfain

OGMS application example: Development of OAE OAE: Ontology of Adverse Events OAE ‘adverse event’: –= def. a OGMS: ‘pathological bodily process’ that occurs after a medical intervention. –Does not assume causality –‘causal adverse event’ assumes causality >1,000 specific AE terms in OAE now, mapped to MedDRA terms OAE for AE data analysis Ref: Sarntivijai et al., 2012 PLoS ONE

IDO : Infectious Disease Ontology IDO: represent the entire infectious disease domain Interoperability with other disease and health domains IDO-core: by Lindsay Cowell, Barry Smith, and others Courtesy: figure kindly provided by Lindsay Cowell IDO-core Central Terms:

IDO Core-Extension Development Strategy IDO extensions are developed by extending IDO-core OGMS OBIGO BP CL I IDO-Core IDO- Bac IDO- Virus IDO-Sa IDO-Flu IDO-Mal IDO- Par IDO- Fun IDO- Flav IDO- TB IDO- Sch IDO-Asp IDO- Cry Courtesy: figure kindly provided by Lindsay Cowell We developed an IDO extension: Brucellosis Ontology

IDOBRU: Brucellosis Ontology as an IDO Extension Focuses on the domain of zoonotic brucellosis, caused by Gram- negative bacterium Brucella. Incorporates all IDO-core terms, has over 880 Brucella-specific terms, and imports terms from other ontologies. Citation: “Asiyah” Yu Lin, Zuoshuang Xiang, Yongqun He. Brucellosis Ontology (IDOBRU) as an extension of the Infectious Disease Ontology. Journal of Biomedical Semantics Oct 31;2(1):9. PMID:

IDO-core is the top ontology of IDOBRU

Vaccine Ontology (VO) VO: A biomedical ontology in the domain of vaccine and vaccination Support data integration, literature mining, and reasoning Integrated with VIOLIN VIOLIN : a vaccine database and analysis system, including many programs, e.g.: o ~3000 vaccines o Protegen: protective antigens. ~600 o Vaxjo: vaccine adjuvants: > 100 o Vaxign: vaccine design o Widely used by vaccine community Funded by a NIAID R01 grant

Many Ontology Tools developed during VO development Ontology fetching tool Linked ontology data server Mass generation of new terms Ontology community view generator Ontology data analysis

VO Statistics and Development OntoFox to import external terms and axioms from other 16 ontologies Ontorat to generate a large number of terms and axioms automatically VO includes >1000 vaccines for >20 host spp. against various diseases

VO imports OBI terms for vaccine investigation OBI/VO modeling of “vaccine protection assay” Reference: Brinkman et al. (2007). Modeling biomedical experimental processes with OBI. Journal of Biomedical Semantics. 2010, 1(Suppl 1):S7. PMID: OBI: Ontology for Biomedical Investigations ~20 communities involved

Example: Afluria Influenza Vaccine

U of Michigan Ontology Research UM Ontology Working Group: o Members: Marcy Harris, Alla Karnovsky, Frank Manion, Oliver He, Asiyah Yu Lin, Jeff Cowall, … o Activities: Biweekly meetings, … o Developing a Clinical and Translational Research Ontology. UM MCubed pilot award: o Title: Ontology Development and Applications for Clinical and Translational Science o To: Alla, Marcy, and Oliver; Period: 1.5 years UM CTSA: Michigan Institute for Clinical & Health Research (MICHR) o Ontology research needed to integrate huge datasets o Committed to collaborative community effort o One project: Informed Consent Ontology (ICO) (next slide) Case study: Head and neck cancer biorepository

Informed Consent Ontology (ICO) ICO: A prototype, aligned with BFO. Currently focused on research permissions UM CTSA Project Team: Alla Karnovsky, Frank Manion, Marcy Harris, Oliver He, Nick Steneck, Blake Roessler Reference: Development of an Informed Consent Ontology to Support Biobanking. Alla Karnovsky, Frank J. Manion, Oliver He, Terry Weymouth, V. Glenn Tarcea; Lisa Powell, Blake J. Roessler, Nicholas H. Steneck. AMIA 2012 Annual Symposium. Protocol Patient Record Institutional Records IRB/ eResearch IRB/ eResearch Informed Consent Form Subject matter expert view Courtesy: figures kindly provided by Alla Karnovsky and Nickolas Steneck

Clinical Data Integration Required Records of millions of patients in UM Health System (UMHS) Ontology is needed for true clinical data integration Courtesy: figure kindly provided by Jeff Cowall

Acknowledgements Funding: NIH grants R01AI & U54-DA UM MCubed pilot project, MICHR (UM CTSA) Oliver He Group: Zuoshuang “Allen” Xiang “Asiyah” Yu Lin Sirarat Sarntivijai UM Literature Mining Collaborators: Arzucan Özgür Junguk Hur VO Collaborators: Barry, Lindsay, Alan, Bjoern, …. Barry Smith (BFO, OGMS, IDO, VO,...) OBI Consortium: Bjoern Peters Jie Zheng Chris Stoeckert Alan Rutternberg Melanie Courtot, … UM Ontology Working Group Listed in a previous slide Lindsay Cowell (IDO) OGMS Development Team Albert Goldfain Richard Scheuermann, …