1. Vaccine Ontology (VO) Yongqun “Oliver” He Unit for Laboratory Animal Medicine Department of Microbiology and Immunology Center for Computational Medicine and Biology & Comprehensive Cancer Center University of Michigan Medical School Ann Arbor, MI 48109

2. Vaccine Research & Development (R & D) Vaccine: improve immunity to a particular disease 1796: Edward Jenner’s cowpox-based vaccine against smallpox Louis Pasteur: developed several vaccines –Anthrax vaccine (1881), –Rabies Vaccine (1885) Ever increasing Vaccine R&D: –Cost effectiveness –Post-genomic technologies

3. Vaccine Publications in PubMed Vaccine publications have increased exponentially

4. Vaccine Databases Government, e.g. –CDC ( http://www.cdc.gov/vaccines/ ) http://www.cdc.gov/vaccines/ –NIH ( http://www3.niaid.nih.gov/Biodefense/Research/funding.htm ) http://www3.niaid.nih.gov/Biodefense/Research/funding.htm –FDA ( http://www.fda.gov/cber/vaccines.htm ) http://www.fda.gov/cber/vaccines.htm Organizations, e.g. –WHO ( http://www.who.int/immunization_safety/en/ ) http://www.who.int/immunization_safety/en/ –The Vaccines Page ( http://www.vaccines.org/ ) http://www.vaccines.org/ –National Network for Immunization Information: ( http://www.immunizationinfo.org/VaccineInfo/index.cfm ) http://www.immunizationinfo.org/VaccineInfo/index.cfm Academia, e.g., –HIV Vaccine Trials Network: ( http://chi.ucsf.edu/vaccines/ ) http://chi.ucsf.edu/vaccines/ Commercial vaccine companies Focus: knowledge and administration of licensed vaccines or vaccines in clinical trial

5. VIOLIN: Vaccine Investigation and Online Information Network Overall goal: A vaccine research database and vaccine data analysis system Aims: –Curate from publications: vaccines and vaccine candidates in use, clinical trials, and research –Vaccine data mining and comparison –Help vaccine design –Community-based vaccine information network Publically available: http://www.violinet.org/http://www.violinet.org/

7. VIOLIN Database Contents against protect induce made by Focus: gene/protein engineering/response Host Response Host Gene Response Gene Engineer Pathogen Vaccine Gene/ Protein cause disease

8. VIOLIN Statistics 275 vaccines 20 pathogens 129 pathogen genes 530 papers Literature: >24,000 abstracts >10,000 full text articles Literature tools: -- Litesearch -- Vaxpresso: NLP -- Vaxmesh: MeSH -- Vaxlert: Paper alert Data Analysis: ** Vaccine query ** Vaccine genes and antigens ** BLAST ** Vaccine target predication ** Data exchange: VIOLINML

9. Query Example:

10. New! Q: How to predict vaccine targets? Vaxign: Vaccine Design Program Predict vaccine protein and epitope targets  Reverse vaccinology http://www.violinet.org/vaxign

11. What’s Missing in VIOLIN? Lacks efficient ways to let computers answer literature mining question from >160,000 papers. Difficult to establish vaccine-induced host immune response networks. How to deal with it? Solution: Vaccine Ontology!

12. Collaborative VO Development VO is developed as a collaborative effort: –VIOLIN and Vaccine Researchers at U of Michigan (UM) Yongqun “Oliver” He (Interest: Brucella vaccine R&D) Harry Mobley (Interest: E. coli vaccine R&D) UM vaccine informatics and resource advisory committee –Infectious Disease Ontology (IDO, http://www.infectiousdiseaseontology.org/ )http://www.infectiousdiseaseontology.org/ Lindsay Cowell (Duke) Barry Smith (Buffalo) Yongqun “Oliver” He (Michigan) –National Center for Biomedical Ontology (NCBO, http://bioontology.org/ )http://bioontology.org/ Barry Smith (Buffalo) Mark Musen (Stanford) Web site: http://www.violinet.org/vaccineontology/http://www.violinet.org/vaccineontology/

13. Vaccine Ontology (VO) Two forms of VO: –Core VO: general terms for all diseases –Disease-specific extensions: e.g., diseases caused by E. coli & Brucella spp. Utilize the Basic Formal Ontology (BFO), the top- level ontology, developed by Dr. Barry Smith and his associates. Follow OBO Foundry principles, e.g., –Developed in a collaborative effort –Use common relations that are unambiguously defined –Provide procedures for user feedback Reference: Smith B, Ashburner M, Rosse C, Bard J, Bug W, Ceusters W, Goldberg LJ, Eilbeck K, Ireland A, Mungall CJ; OBI Consortium, Leontis N, Rocca-Serra P, Ruttenberg A, Sansone SA, Scheuermann RH, Shah N, Whetzel PL, Lewis S. (2007). The OBO Foundry: coordinated evolution of ontologies to support biomedical data integration. Nat Biotechnol 25 (11): 1251-5.

14. Core Vaccine Ontology > 500 vaccine-related terms included * *

15. Question: what are live attenuated Brucella vaccines? Should be both “Brucella vaccine” AND “live attenuated vaccine” This VO contains two: B. abortus vaccine RB51 and B. abortus vaccine strain 19 VO allows automated reasoning A Typical User Case Study

16. What are immune responses induced by live attenuated Brucella vaccines? The question becomes: What are the immune responses induced by B. abortus vaccines RB51 and strain 19? Do they induce any immune responses defined by VO? If reported  retrieve & analyze Not yet studied  predict & analyze Immune Response Terms in VO

17. VO-based NLP Literature Mining A VO-natural language processing (NLP) program is being developed –Retrieve VO-specified vaccine data from literature –Expand existing VO by finding more vaccine- related terms and relationships –Study vaccine-induced host immune response networks Collaboration with NCIBI: –NCIBI: National Center for Integrative Biomedical Informatics (http://www.ncibi.org)http://www.ncibi.org Drs. David States, Brian Athey, and Gil Omenn –NCIBI processes all PubMed papers by NLP

18. More Tasks & Questions Assign gene names to VO terms. Relationships with Ontologies: IDO, GO, OBI Collaborate with OBI (Bjoern Peters, Richard Scheuermann) -- vaccine investigation, experiment … VO application in VIOLIN DB: add instances to VO  Knowledgebase Vaccine Semantic Web?

19. Acknowledgements Infectious Disease Ontology (IDO): Barry Smith (NCBO, Buffalo) Lindsay Cowell (Duke) Oliver He Lab at UM: Zuoshuang Xiang Thom Todd Fang Chen Andrew Hodges G. Bill Jourdian Charlie Larson Kimberly Ku Bethany Kovacic Elizabeth Olenzek Boyang Zhao University of Michigan (UM): NCIBI: David States Brian Athey Gil Omenn Harry Mobley Steve Qin Howard Rush Lesley Colby Yuying Tian Janet Gilsdorf http://www.violinet.org/vaccineontology

20. Brucellosis Ontology Basic Idea: Extend IDO to brucellosis:

21. Brucellosis Ontology