This document discusses the development of an ontology to support influenza research and surveillance. It describes two case studies of influenza outbreaks and outlines a research agenda to connect genomic and epidemiological data through an influenza ontology. The document outlines the initial steps taken to develop an influenza ontology, including collecting metadata terms, identifying related ontologies, and formalizing terms. Future work is noted to complete the ontology development and validate it using real influenza data.

1. © 2006 The MITRE Corporation. All rights reserved
Ontology Support for
Influenza Research and
Surveillance
Joanne Luciano, PhD,
Lynette Hirschman, PhD, Marc Colosimo, PhD
Approved for Public Release; Distribution Unlimited.
28 April 2008 Case Number 08-0738

2. © 2008 The MITRE Corporation. All rights reserved
Approved for Public Release; Distribution Unlimited. 28 April 2008 Case Number 08-0738
2
Case Study 1: Indonesia
■ Possible Human to Human transmission of H5N1 (May 2006)
■ Samples were collected and epidemiological data obtained
– Know who got sick and their relationship to each other
– Know when they got sick and if they died
– Have some public sequence data from that time
■ It is not known if these sample are from these people!
Public Sequence Data
30 Aug 2006
A/Indonesia/CDC595/2006 (2006-05-09)
A/Indonesia/CDC594/2006 (2006-05-10)
….
A/Indonesia/CDC625L/2006 (2006-05-22)
A/Indonesia/CDC644/2006 (2006-05-30)
WHO Nature
Same person ?
GenBank
isolation_source="gender:M; age:32;
Lung Aspirate"
Metadata
23 May 2006
Metadata
12 Jul 2006
Butler “Family tragedy spotlights flu mutations
“ Nature 442, 114 - 115 (12 Jul 2006) News

3. © 2008 The MITRE Corporation. All rights reserved
Approved for Public Release; Distribution Unlimited. 28 April 2008 Case Number 08-0738
3
Case Study 2: UK
■ Outbreak of H5N1 in the UK at a turkey farm Feb 1, 2007
■ What is the source of the outbreak?
– Contact with infected wild birds?
■ But turkeys were in an enclosed “biosecure” unit
■ No H5N1 detected in the region in the 2 previous months
– Govt. veterinarian suggested turkey meat from Hungary might be
source of infection
■ Turkey farm is adjacent to a poultry packing plant that had processed
poultry products from Hungary
■ Hungary had reported an H5N1 outbreak 2 weeks earlier
■ Sequence data showed that strain infecting the turkeys was
99.96% identical to strain that had infected Hungarian birds
■ Conclusion: Infected Hungarian poultry was source of H5N1
infection
– Open question (relevant to food defense):
how did H5N1 spread from processing plant to live turkeys?

4. © 2008 The MITRE Corporation. All rights reserved
Approved for Public Release; Distribution Unlimited. 28 April 2008 Case Number 08-0738
4
Research Agenda
■ Reference Database (Sequences & Metadata)
– What metadata to collect?
– Where to find data and how to connect different sources
(bridging the gap)?

5. © 2008 The MITRE Corporation. All rights reserved
Approved for Public Release; Distribution Unlimited. 28 April 2008 Case Number 08-0738
5
Genomic
Sequence Data
Systems Biology
Demographic data
Clinical data
Research Question: Bridging the Gap -
Connecting Genomics and Epidemiology
Geospatial data
Temporal data
Pathogenicity
Host
Epidemiology:
Occurrence of
Disease in
Host
Genomics:
Genes of
Pathogen
Influenza Ontology

6. © 2008 The MITRE Corporation. All rights reserved
Approved for Public Release; Distribution Unlimited. 28 April 2008 Case Number 08-0738
6
■ Identify the right collaborators
■ Collect metadata terms
■ Identify resources for that include these terms
■ Regularize metadata
– Generate a controlled vocabulary (terms)
■ Validate subset with BioHealthBase CEIRS data
■ Iterate, review with community, publish
■ Integrate Influenza ontology into workflow
Influenza Ontology: Development

7. © 2008 The MITRE Corporation. All rights reserved
Approved for Public Release; Distribution Unlimited. 28 April 2008 Case Number 08-0738
7
Influenza Ontology First Draft:
Community
■ BioHealthBase: NIAID Influenza Database
Point of Contact for
– Centers of Excellence for Influenza Research and Surveillance (CEIRS)
■ Research: Emory, Mt Sinai, St. Jude, Univ. of Rochester
■ Surveillance: St. Jude, UCLA, Univ. of Minnesota
– Los Alamos National Laboratory (LANL)
■ Gemina: Category A-C Pathogen Database
Point of contact for
– Children’s Hospital Boston
– Johns Hopkins University
■ MITRE
Collaboration with BioHealthBase and Gemina

8. © 2008 The MITRE Corporation. All rights reserved
Approved for Public Release; Distribution Unlimited. 28 April 2008 Case Number 08-0738
8
Influenza Ontology First Draft:
Identify metadata
200 controlled vocabulary terms
covering several fields

9. © 2008 The MITRE Corporation. All rights reserved
Approved for Public Release; Distribution Unlimited. 28 April 2008 Case Number 08-0738
9
Reuse of existing ontologies & metadata standards
OBI – Ontology of Biomedical Investigations
EnvO – Environmental Ontology (habitat of pathogen)
GAZ – Gazeteer (geographic locations)
FMA – Foundational Model of Anatomy
DC – Dublin Core (publication metadata)
PATO – Phenotype
SO – Sequence Ontology (sequence features)
Cell – Cell Ontology (types of cells)
DO – Disease Ontology
IDO – Infectious Disease Ontology
Influenza Ontology First Draft:
Metadata resources

10. © 2008 The MITRE Corporation. All rights reserved
Approved for Public Release; Distribution Unlimited. 28 April 2008 Case Number 08-0738
10
Influenza Ontology First Draft
Excel Spreadsheet
Initial steps:
• Collect metadata terms
• Map and align terms
• Group related information
• Identify and define relationships
• Identify external ontologies
Formalize
OBO-Edit: Ontology Editing Tool
Formalize:
• Normalize terms into a CV
• Issue unique identifiers
• Instantiate class hierarchy
• Define properties and values
• Link to external ontology
terms
Status: We have just started the formalization step.

11. © 2008 The MITRE Corporation. All rights reserved
Approved for Public Release; Distribution Unlimited. 28 April 2008 Case Number 08-0738
11
Future Work
Ontology development
■ Complete formalization process
■ Validate subset with data from BioHealthBase
– Circulate for review and comments
■ Use ontology to annotate influenza data

12. © 2008 The MITRE Corporation. All rights reserved
Approved for Public Release; Distribution Unlimited. 28 April 2008 Case Number 08-0738
12
Team
■ BioHealthBase (UT Southwestern Medical Center)
– Burke Squires
– Richard Scheuermann
■ Institute of Genome Sciences/Gemina (U. Maryland
Baltimore)
– Lynn Schriml
■ MITRE
– Joanne Luciano
– Lynette Hirschman
– Marc Colosimo