1. 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

2. 2 BioHealthBase BRC Bioinformatics Resource Centers for Biodefense and Emerging/Re-emerging Infectious Diseases program funded by NIAID ( www.brc-central.org) www.brc-central.org –8 centers funded BioHealthBase (www.biohealthbase.org) is an integrated resourcewww.biohealthbase.org –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

3. 3 BHB Flu - Home Page & Data Summary www.biohealthbase.org

4. 4 BHB Flu - Query & Detail Record

5. 5 BHB Flu - Sequence Conservation

6. 6 BHB Flu - Immune Epitopes

7. 7 BHB Flu - Reactome

8. 8 3D Visualization 302 Flu structures 702 Mtb structures

9. 9 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.

10. 10 IDO scales of granularity Host-pathogen interactions occurs at a variety of scales –Ecosystem –Organism –Organ –Cell –Molecule Surveillance Pathogenesis

11. 11 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)

12. 12 IDO scales & branches ScaleIndependent Continuant Dependent ContinuantOccurrent 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 cellInfected (quality), activated, susceptible (disposition) antigen presentation, proliferation, phagocytosis, cytoxicity, apoptosis Molecule Glyoxalase, catalase, recAdetoxification (role), DNA lesion recognition, DNA repair, transport catalysis, binding, transport

13. 13 Relationship between experiments and biological knowledge Primary isolate Amplified specimen Amplified specimens Manipulated variable Analyte levels Responding variable Variables Correlation/ cause-and-effect OBI:biomaterial transformation OBI:assay OBI:data transformation

14. 14 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