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Workshop on Infectious Disease Ontology

Influenza Informatics in the BioHealthBase Bioinformatics Resource Center

Richard H. Scheuermann, Ph.D.Department of Pathology

U.T. Southwestern Medical Center

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BioHealthBase BRC

• Bioinformatics Resource Centers for Biodefense and Emerging/Re-emerging Infectious Diseases program funded by NIAID (www.brc-central.org)

– 8 centers funded

• BioHealthBase (www.biohealthbase.org) is an integrated resource– Interrelates data from NCBI, UniProt, Pfam, and other sources

• Direct summary and visualization of integrated data• Linkouts to source data sites for additional data details

– Allows “one-stop shopping” for science researchers

• BioHealthBase provides value-added, pre-computed data– Valuable processed data not available elsewhere

• Protein structural and functional predictions• Sequence alignment and polymorphism analysis• Predicted immunological epitopes

• BioHealthBase provides a forum for displaying collaborative data– Pathways with Reactome; epitopes with Immune Epitope Database

• BioHealthBase emphasizes host-pathogen interactions– Pathogen effects on host cellular pathways– Immune response to pathogen infection– Support of research related to vaccine, therapeutic and diagnostic development

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BHB Flu - Home Page & Data Summary

www.biohealthbase.org

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BHB Flu - Query & Detail Record

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BHB Flu - Sequence Conservation

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BHB Flu - Immune Epitopes

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BHB Flu - Reactome

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3D Visualization

302 Flu structures702 Mtb structures

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CEIRS

• Motivation– lay the groundwork for the

development of new and improved control measures

– understanding how influenza viruses evolve, adapt and transmit

– identifying immunological factors that determine disease outcome

• Research Areas– Research Area 1: Animal Influenza

Surveillance Conduct prospective international and/or domestic animal influenza surveillance for the rapid detection and characterization of influenza viruses with pandemic potential.

– Research Area 2: Pathogenesis and Host Response Research Conduct research to enhance understanding of the molecular, ecological, and/or environmental factors that influence pathogenesis, transmission, and evolution of influenza viruses; and characterize the protective immune response.

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IDO scales of granularity

• Host-pathogen interactions occurs at a variety of scales

– Ecosystem

– Organism

– Organ

– Cell

– Molecule

Surveillance

Pathogenesis

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IDO scales & terms

• Ecosystem - transmission, geographic location, population density, routes of migration, specimen isolation procedure, specimen isolation source, vector, carrier, reservoir, environment, prevalence

• Organisms - latency, reactivation, disease progression, innate immune response, adaptive immune response, cytokine storm, symptoms (consumption, night sweats, fever, weight loss, wasting, immunosuppression), sterile eradication, delayed-type hypersensitivity, vaccine, surrogate markers of protection, viral load, animal model, pathogenesis, route of treatment, protection, resistance, sensitive, tuberculosis, human immunodeficiency syndrome, infective endocarditis

• Organ - granuloma, caseous necrosis, inflammation, endocarditis, lung, peripheral blood, cavity, pericavitary tissue, distant lung, immune system, mucosa, gut lumen, lymph node, inductive site, effector site, tissue damage,

• Cell - phagocytosis, pathogen sensing, cytotoxicity, T cells, B cells, macrophages, dendritic cells, bacterium, antibiotic drug, antiviral drug, cell autonomous apoptosis, bystander apoptosis, antigen presentation, infected, activated

• Molecules - transport/binding proteins, cell wall synthesis, two component systems, chaperones, detoxification (glyoxalase), DNA repair, lipid biosynthesis, fatty acid degradation, cell surface variable proteins, methylglyoxal, advanced glycation end products, reactive oxygen intermediates (ROIs)

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IDO scales & branches

Scale Independent Continuant

Dependent Continuant Occurrent

Ecosystem specimen isolation source, environment

vector (role), carrier (role), population density, routes of migration (?), host (role), pathogen (role), source (?), temperature

transmission, migration, specimen isolation process, specimen isolation event

Organism NCBI taxonomy, vaccine preparation,

healthy, sick, animal model (role), viral load, latent (state), sterile eradication (state), symptoms (quality), immunogen (role), adjuvant (role), pathogen (disposition), resistant (disposition)

pathogenesis, reactivation, progression, immune response, vaccination

Organ FMA (mucosal organ - lung, secondary lymphoid organ - lymph node), pericavitary tissue, abssess

viral load (quality), inductive site (role), effective site, inflamed (quality), granuloma (quality), caseous necrosis (quality)

inflammation, tissue damage, necrosis

Cell T cell, dendritic cell Infected (quality), activated, susceptible (disposition)

antigen presentation, proliferation, phagocytosis, cytoxicity, apoptosis

Molecule Glyoxalase, catalase, recA detoxification (role), DNA lesion recognition, DNA repair, transport

catalysis, binding, transport

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Relationship between experiments and biological knowledge

Primary isolate

Amplified specimen

Amplified specimensManipulated variable

Analyte levelsResponding variable

Variables

Correlation/cause-and-effect

OBI:biomaterialtransformation

OBI:assay OBI:datatransformation

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Acknowledgments

• U.T. Southwestern– Burke Squires– Victoria Hunt– Shubhada Godbole– Roger Chang– Jyothi Noronha– Feng Luo– Cathy Spranger– Kevin McIver

• LANL– Catherine Macken– Mira Dimitrijevic

• Co-investigators– Barbara Mann (UVA)– Adolfo Garcia-Sastre (MSSM)– Hillary Morrison (MBL)– Louis Weiss (Albert Einstein)– Ellen Vitetta (UTSW)

• Amar– X. Wei– David Deng

• DMID/NIAID– Valentina DiFrancesco

• Northrop Grumman– Ed Klem– Kevin Biersack– Carey Gire– Jason Lucas– Sharmila Vattikuti– Sanjeev Kumar– Paul Shrabstein– Surabhi Sharma– Tammie Ajayi– Aihui Wang– Zuoming Deng– Jianjun Wang– DeWayne Ejikeme

• Vecna– James Wolowicz– Chris Larsen– Al Ramsey

• Reactome– Marc Gillespie– Peter D-Eustachio– Lincoln Stein

• MITRE– Joanne Luciano– Lynette Hirschman