8 December 2010 Richard H. Scheuermann, Ph.D. Department of Pathology

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Bioinformatics Resource Centers Influenza Research Database (IRD) Virus Pathogen Database and Analysis Resource ( ViPR ). 8 December 2010 Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern Medical Center. NIAID Scientific Resources. - PowerPoint PPT Presentation

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Bioinformatics Resource CentersInfluenza Research Database (IRD)Virus Pathogen Database and Analysis Resource (ViPR)8 December 2010

Richard H. Scheuermann, Ph.D.Department of PathologyU.T. Southwestern Medical Center

www.fludb.orgNIAID Scientific Resources

http://www.niaid.nih.gov/labsandresources/resources/Pages/default.aspx www.fludb.orgDMID Resources List

www.fludb.orgDMID BRC Resources

www.fludb.orgCategory A Pathogens

www.fludb.orgCategory B Pathogens

www.fludb.orgCategory A Pathogens

www.fludb.orgDMID BRC Resources

www.fludb.orgBRC Portal

www.fludb.orgViPR

www.viprbrc.orgwww.fludb.orgInfluenza Research Database (IRD)

www.fludb.orgwww.fludb.orgIRD Home Page

www.fludb.orgPublic Health Impact of InfluenzaSeasonal flu epidemics occur yearly during the fall/ winter months and result in 3-5 million cases of severe illness worldwide.More than 200,000 people are hospitalized each year with seasonal flu-related complications in the U.S.Approximately 36,000 deaths occur due to seasonal flu each year in the U.S. Populations at highest risk are children under age 2, adults age 65 and older, and groups with other comorbidities. Source: World Health Organization - http://www.who.int/mediacentre/factsheets/fs211/en/index.html

www.fludb.org13Source: World Health Organization - http://www.who.int/mediacentre/factsheets/fs211/en/index.html Known flu pandemics occurring during the 20th and 21st centuries1) 1918 flu pandemic (Spanish flu) - Subtype H1N1- the most severe pandemic- estimated to have claimed between 2.5% to 5.0% of the worlds population (20 > 100 million deaths)

2) Asian flu (1957 - 1958)- Subtype H2N2- 1 > 1.5 million deaths

3) Hong Kong flu (1968 - 1969)- Subtype H3N2- between 750,000 and 1 million deaths

4) 2009 H1N1- Subtype H1N1- > 16,000 deaths as of March 2010

www.fludb.org14Source: http://en.wikipedia.org/wiki/InfluenzaInfluenza Virus

Orthomyxoviridae familyNegative-strand RNASegmentedEnveloped8 RNA segments encode11 proteinsClassified based on serology of HA and NAwww.fludb.orgIRD Overview

www.fludb.orgwww.fludb.orgData - sequence

IRD Datawww.fludb.orgData - surveillance

IRD Datawww.fludb.orgSurveillance detail page

Implicit versus explicit semanticswww.fludb.orgStrain detail page

www.fludb.orgSegment detail page 1

www.fludb.orgSegment detail page 2

www.fludb.orgSegment search

taxonomygazeteerwww.fludb.orgData 3D protein structure

IRD Datawww.fludb.org3D protein structure search results

www.fludb.org3D Structures & IntegrationVisualize protein structure in 3DDisplay sequence conservation heat map on the structureHighlight sequence features (epitopes, etc.)Download highlighted protein structure imagewww.fludb.org3D Structure

www.fludb.orgAnalysis and Visualization Tools

www.fludb.org

My Workbenchwww.fludb.orgIRD SummaryFunded by U.S. National Institute of Allergy and Infectious Diseases (NIAID)Free and open access with no use restrictionsDeveloped by a team of research scientists, bioinformaticians and professional software developersComprehensive collection of public dataNovel derived data, novel analytical tools, unique functionsIntegration Integration Integrationwww.fludb.org www.fludb.org31U.T. SouthwesternRichard ScheuermannBurke SquiresJyothi NoronhaVictoria HuntShubhada GodboleBrett PickettMengya LiuMSSMAdolfo Garcia-SastreEric BortzGina ConenelloPeter PaleseVecnaChris LarsenAl RamseyLANLCatherine MackenMira DimitrijevicU.C. DavisNicole BaumgarthNorthrop GrummanEd KlemMike AtassiKevin BiersackJon DietrichWenjie HuaWei JenSanjeev KumarXiaomei LiZaigang LiuJason LucasMichelle LuBruce QuesenberryBarbara RotchfordHongbo SuBryan WaltersJianjun WangSam ZarembaLiwei ZhouIRD SWGGillian Air, OMRFCarol Cardona, Univ. MinnesotaAdolfo Garcia-Sastre, Mt SinaiElodie Ghedin, Univ. PittsburghMartha Nelson, FogartyDaniel Perez, Univ. MarylandGavin Smith, Duke SingaporeDavid Spiro, JCVIDave Stallknecht, Univ. GeorgiaDavid Topham, RochesterRichard Webby, St JudeUSDADavid Suarez Sage AnalyticaRobert TaylorLone SimonsenCEIRS Centers

Acknowledgementswww.fludb.org31SFVT approachVT-1I F D R L E T L I LVT-2I F N R L E T L I LVT-3I F D R L E T I V LVT-4L F D Q L E T L V SVT-5I F D R L E N L T LVT-6I F N R L E A L I LVT-7I Y D R L E T L I LVT-8I F D R L E T L V LVT-9I F D R L E N I V LVT-10I F E R L E T L I LVT-11 L F D Q M E T L V SInfluenza A_NS1_nuclear-export-signal_137(10)

Identify regions of protein/gene with known structural or functional properties Sequence Features (SF)an alpha-helical region, the binding site for another protein, an enzyme active site, an immune epitopeDetermine the extent of sequence variation for each SF by defining each unique sequence as a Variant Type (VT)High-level, comprehensive grouping of all virus strains by VT membership for each SF independentlyInfluenza A_NS1_alpha-helix_171(17)www.fludb.orgInfluenza A NS1 protein (PDB 2GX9) crystal structure showingNuclear Export Signal Sequence Feature (SF) highlighted in RedAlpha-helix SF highlighted in greenAmino acid alignment with colors showing variation within nuclear export signal regionEach sequence with 1+ substitutions comprises a unique fingerprint or Variant Type (VT)A set of unique sequence substitutions existing within any defined region is a sequence feature variant type (SFVT) Statistical analyses on SFVTs can identify genotype-phenotype relationships32

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