Vaccine Ontology (VO) Yongqun “Oliver” He Unit for Laboratory Animal Medicine Department of...
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Vaccine Ontology (VO)
Yongqun “Oliver” He
Unit for Laboratory Animal MedicineDepartment of Microbiology and Immunology
Center for Computational Medicine and Biology& Comprehensive Cancer Center
University of Michigan Medical SchoolAnn 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
Vaccine publications have increased exponentially
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20000
40000
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120000
140000
160000
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1890-1950
1960 1970 1980 1990 2000 2008
Time (Year)
No
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ine
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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
against
protectinduce
made by
Focus: gene/protein engineering/response
Host Host
Response Host GeneResponse
GeneEngineerPathogen
VaccineGene/
Protein causedisease
VIOLIN Statistics
275 vaccines20 pathogens129 pathogen
genes530 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
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 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.
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
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 & analyzeNot yet studied predict & analyzeImmune Response Terms in VO
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)
• 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
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