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VIOLIN and VO (Vaccine Ontology) Yongqun “Oliver” He Unit for Laboratory Animal Medicine Department of Microbiology and Immunology Center for Computational Medicine and Bioinformatics University of Michigan Medical School Ann Arbor, MI 48109 Outline • VIOLIN: a web-based vaccine research database and analysis system • Vaccine Ontology (VO) development • VO applications VIOLIN: Vaccine Investigation and Online Information Network • Summary: A vaccine research database and vaccine data analysis system • Aims: – Curate data from publications: licensed vaccines, vaccines in clinical trials, and vaccines in research – Vaccine data mining and comparison – Vaccine design – Study vaccine-induced immune networks – Build community-based vaccine information network • Publically available: http://www.violinet.org/ VIOLIN Programs VIOLIN Database Contents Host Response Host protect cause disease Host Gene Response induce Vaccine Gene/ Protein against made by Pathogen Gene Engineer Focuses: molecular engineering & mechanisms VIOLIN Statistics 2481 vaccines 1930 licensed vaccines 153 pathogens / diseases ~ 600 protective antigens 1426 references > 24,000 abstracts/full text Aim: Include all licensed vaccines worldwide and selected vaccines in clinical trials and research http://www.violinet.org/stat.php Selected VIOLIN Publications • Original Publication: Xiang Z, Todd T, Ku KP, Kovacic BL, Larson CB, Chen F, Hodges AP, Tian Y, Olenzek EA, Zhao B, Colby LA, Rush HG, Gilsdorf JR, Jourdian GW, He Y. VIOLIN: Vaccine Investigation and Online Information Network. Nucleic Acids Res. 2008 Jan;36:D923-8. • Demo using Brucella: He Y, Xiang Z. Bioinformatics analysis of Brucella vaccines and vaccine targets using VIOLIN. Immunome Res. 2010 Sep 27;6 Suppl 1:S5. • VIOLIN Vaxign (Vaccine Design) Program: He Y, Xiang Z, Mobley HLT. Vaxign: the first web-based vaccine design program for reverse vaccinology and an application for vaccine development.J Biomed Biotechnol. 2010;2010:297505. • VIOLIN Protegen (Protective Antigen) program: Yang B, Sayers S, Xiang Z, He Y. Protegen: a web-based protective antigen database and analysis system. Nucleic Acids Research. 2010. 2010 Oct 19. • Five papers using VO – No formal VO paper yet, still work on it. VO: Vaccine Ontology • VO: a biomedical ontology in the vaccine domain. • Aims: vaccine data representation and automated reasoning • Utilize the Basic Formal Ontology (BFO) as the top-level ontology • 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. Collaborative VO Development • VO is developed as a collaborative effort: – VIOLIN and Vaccine Researchers at U of Michigan (UM) • • • • Yongqun “Oliver” He (Interest: Bioinformatics & Brucella vaccine R&D) Harry Mobley (Interest: E. coli vaccine R&D) UM vaccine informatics and resource advisory committee NCIBI: National Center for Integrative Biomedical Informatics – Infectious Disease Ontology (IDO, http://www.infectiousdiseaseontology.org/ ) • Lindsay Cowell (Duke) • Barry Smith (Buffalo) – National Center for Biomedical Ontology (NCBO, http://bioontology.org/ ) • Barry Smith (Buffalo) • Trish Whetzel / Mark Musen (Stanford) – Ontology for Biomedical Investigations (OBI) • • • • Bjoern Peters (La Jolla) Richard H. Scheuermann (Texas) Alan Ruttenberg (Science Commons) Ryan Brinkman / Melanie Courtot (BC, Canada – PCIRN) – Gene Ontology • Alexander Diehl (MGI, Jackson Laboratory) • Chris Mungall http://www.violinet.org/vaccineontology VO Statistics Import other ontology terms using OntoFox: http://ontofox.hegroup.org/ Vaccine Definition Definition : A vaccine is a processed material with the function that when administered, it prevents or ameliorates a disorder in a target organism by inducing or modifying adaptive immune responses specific to the antigens in the vaccine. Vaccination Definition Vaccine Immunization (or: artificial active immunization) • Difference between vaccination and ‘vaccine immunization’: o Vaccination does not consider the outcome o Immunization consider the outcome • Superclasses: has_specified_input_of some vaccine realizes some (‘host role’ and inheres_in some organism) realizes some (‘immunization target role’ and inheres_in some disorder) Example: Afluria Influenza Vaccine age has_ quality bearer _of Bob (a human) Influenza virus vaccine host role bearer_of quality_is_measured_as age measurement datum (value: 6 unit: month) has_ participant plan specification has_part dose specification viral pathogen target role intramuscular vaccination is_a measurement data realizes is_about is_ realized -by has_ quality inactivated adaptive immune response has_participant realizes has_part is_specified_ input_of Afluria-1 has_participant viral vaccineinduced immunization has_ bearer_of some specified _output ‘acquired immunity to Influenza virus’ _of is_a Flu vaccine has_part is_ manufactured _by CSL Limited chicken egg protein allergen bearer_of vaccine allergen disposition Vaccines in VO Other vaccines: 508 Total: 768 >1000 vaccines to be added to VO soon, including licensed animal vaccines and curated vaccines in VIOLIN. Vaccines by host & diseases Protection assay with Brucella vaccine RB51 using VO and OBI age intraperitoneal vaccination is a vaccination 8 weeks B. abortus strain 2308 is a Bacterium is_ realized_ by host role is_ realized_ by inheres_in has_part vaccinated Balb/c mouse is a Mus musculus is_quality_ measured_ as has_ specified_ input RB51 is a vaccine has_quality pathogen role is_ realized _by has_ has_ specified_ specified_ output input alive derives_from female is a biological sex inheres_in has_specified_input is_quality_measured_as B. abortus strain RB51 has_ quality Balb/c mouse is a Mus musculus has_ quality Brucella abortus strain 2308 is a Bacterium inheres_in has_ specified_ is_quality_ input measured_as intraperitoneal pathogen challenge is a pathogen challenge has_ specified_ input 10^5 CFU has_ specified_ output pathogen challenged Balb/c mouse is a mouse Balb/c mouse post vaccination is a mouse has_specified_input 10^8 CFU 8 weeks has_ duration has_ specified_ output laboratory animal care Balb/c mouse post challenge is a Mus musculus has_ specified_ output laboratory animal care has_duration 1 week has_specified_input is_quality_measured_as CFU reduction 1.5 log CFU is a measurement datum has_ specified_ output CFU reduction assay independent variable specification is_about time Reference: He Y, Xiang Z, Todd T, Courtot M, Brinkman R, Zheng J, Stoeckert CJ, Malone J, Rocca-Serra P, Sansone S, Fostel J, Soldatova LN, Peters B, Rutternberg A. Ontology representation and ANOVA analysis of vaccine protection investigation. Proceeding of Bio-Ontologies 2010: Semantic Applications in Life Sciences, ISMB, July 9-10, 2010. Boston, MA, USA. Full length paper. VO Applications • Integrate VIOLIN vaccine data • Help VIOLIN relational database design • Generate vaccine instance data for data exchange purpose • Enhance vaccine literature mining power o Indexing of PubMed vaccine papers o Vaccine induced network VO Improve Vaccine Literature Mining With VO knowledge, the PubMed search results are significantly improved VO-based Literature Mining of IFNG Network References: • Ozgur A, Xiang Z, Radev D, He Y. Mining of vaccine-associated IFN-γ gene interaction networks using the Vaccine Ontology. Proceeding of Bio-Ontologies 2010: Semantic Applications in Life Sciences, ISMB, July 9-10, 2010. Boston, MA, USA. Full length paper. • Ozgur A, Xiang Z, Radev D, He Y. Literature-based discovery of IFN- and vaccine-mediated gene interaction networks. Journal of Biomedicine and Biotechnology. Volume 2010 (2010), Article ID 426479, 13 pages. [PMID: 20625487] 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 • Samantha Sayers • Kanika Kochhal Funding: NIH-NIAID R01AI081062 University of Michigan University of Michigan (UM): • NCIBI: • Brian Athey • Gil Omenn • Harry Mobley • Howard Rush • Lesley Colby • Janet Gilsdorf BFO IDO OBI GO NCBO OBO Foundry