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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1960 1970 1980 1990 2000 2008

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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

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 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.

Core Vaccine Ontology

> 500 vaccine-related terms included

*

*

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

Brucellosis Ontology

• Basic Idea: Extend IDO to brucellosis:

Brucellosis Ontology