Transcript Flu Presentation - people.duke.edu

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
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Bioinformatics Resource Centers for Biodefense and Emerging/Re-emerging
Infectious Diseases program funded by NIAID (www.brc-central.org)
– 8 centers funded
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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
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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
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BioHealthBase provides a forum for displaying collaborative data
– Pathways with Reactome; epitopes with Immune Epitope Database
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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 structures
702 Mtb structures
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CEIRS
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Motivation
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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
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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
Surveillance
– Organism
– Organ
Pathogenesis
– Cell
– Molecule
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IDO scales & terms
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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
OBI:biomaterial
transformation
Amplified specimen
Amplified specimens
Manipulated variable
OBI:assay
Analyte levels
Responding variable
Variables
OBI:data
transformation
Correlation/
cause-and-effect
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Acknowledgments
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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
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