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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 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 Vaccine Publications in PubMed 200000 No. of Vaccine Publications 180000 160000 140000 120000 100000 80000 60000 40000 20000 0 18901950 1960 1970 1980 1990 2000 2008 Time (Year) Vaccine publications have increased exponentially Vaccine Databases • Government, e.g. – CDC ( http://www.cdc.gov/vaccines/ ) – NIH ( http://www3.niaid.nih.gov/Biodefense/Research/funding.htm ) – FDA ( http://www.fda.gov/cber/vaccines.htm ) • Organizations, e.g. – WHO ( http://www.who.int/immunization_safety/en/ ) – The Vaccines Page ( http://www.vaccines.org/ ) – National Network for Immunization Information: ( http://www.immunizationinfo.org/VaccineInfo/index.cfm ) • Academia, e.g., – HIV Vaccine Trials Network: ( http://chi.ucsf.edu/vaccines/ ) • Commercial vaccine companies • Focus: knowledge and administration of licensed vaccines or vaccines in clinical trial 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/ VIOLIN Database Contents Host Response Host protect cause disease Host Gene Response induce Vaccine Gene/ Protein against made by Pathogen Gene Engineer Focus: gene/protein engineering/response VIOLIN Statistics 275 vaccines 20 pathogens 129 pathogen genes 530 papers Data Analysis: ** Vaccine query ** Vaccine genes and antigens ** BLAST ** Vaccine target predication ** Data exchange: VIOLINML Literature tools: Literature: >24,000 abstracts >10,000 full text articles -- Litesearch -- Vaxpresso: NLP -- Vaxmesh: MeSH -- Vaxlert: Paper alert Query Example: New! Q: How to predict vaccine targets? Vaxign: Vaccine Design Program Predict vaccine protein and epitope targets Reverse vaccinology http://www.violinet.org/vaxign 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! 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/ ) • Lindsay Cowell (Duke) • Barry Smith (Buffalo) • Yongqun “Oliver” He (Michigan) – National Center for Biomedical Ontology (NCBO, http://bioontology.org/ ) • Barry Smith (Buffalo) • Mark Musen (Stanford) • Web site: http://www.violinet.org/vaccineontology/ 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 toplevel 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. Core Vaccine Ontology * * > 500 vaccine-related terms included A Typical User Case Study 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 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? Immune Response Terms in VO If reported retrieve & analyze Not yet studied predict & analyze 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 vaccinerelated terms and relationships – Study vaccine-induced host immune response networks • Collaboration with NCIBI: – NCIBI: National Center for Integrative Biomedical Informatics (http://www.ncibi.org) • Drs. David States, Brian Athey, and Gil Omenn – NCIBI processes all PubMed papers by NLP 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? Acknowledgements 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 Infectious Disease Ontology (IDO): • Barry Smith (NCBO, Buffalo) • Lindsay Cowell (Duke) http://www.violinet.org/vaccineontology Brucellosis Ontology • Basic Idea: Extend IDO to brucellosis: Brucellosis Ontology