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1
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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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