ViPR SWG Meeting 17NOV2015

Transcription

1 ViPR SWG Meeting 17NOV2015

2 Introduction and Usage

3 ViPR Development Team J. Craig Venter Institute Brian Aevermann Suman Das Doug Greer Alex Lee Brian Reardon Reed Shabman Lucy Stewart Tim Stockwell Yun Zhang Vecna Chris Larsen Guangyu Sun Northrop Grumman Ed Klem Mary Shaffran Zhiping Gu Sherry He Sanjeev Kumar Xiaomei Li Lei Tong Bryan Walters Verle Wright Sam Zaremba Hongtao Zhao

4 ViPR Advisors Co-investigators Nicole Baumgarth (UC Davis) David Knipe (Harvard) Richard Kuhn (Purdue) Catherine Macken (U Aukland) Slobadan Paessler (UTMB) Daniel Perez (UGA) NIAID Alison Yao Scientific Working Group Gillian Air (OUHSC) Ralph Baric (UNC) Ruben Donis (CDC) Naomi Forrester (UTMB) Adolf Garcia-Sastre (Mt. Sinai) Elodie Ghedin (NYU) Elliot Lefkowitz (UAB) Phil Pellet (Wayne State) David Topham (URMC) Richard Webby (St. Jude)

5 ViPR SWG Agenda Introduction (10 min) ViPR usage report (15 min; Richard Scheuermann) Website usage - Google Analytics Workbench accounts Literature citations Recent enhancements (5 min; Alex Lee) Rotavirus genotyping Coronavirus ortholog grouping CIPRES interface Ebola portal and D68 sequence searches GO enrichment AWS cloud migration SWG experience with pre-meeting exercises (35 min; Richard Scheuermann) Round-robin for each of the SWG members Comments from VBRC co-investigators

6 ViPR SWG Agenda New project - virus orthology and naming consistency as applied to HSV (20 min; Doug Greer) Observations about nomenclature inconsistencies Use of ortholog groups Taxonomic span of ortholog groups What can we do with this information? New project support for antiviral drug research (20 min; Brian Reardon) Host factor component in general New project with a focus on antiviral drug research Planned enhancements (10 min; Brian Aevermann) New projects that we just discussed Metadata harmonization User-provided metadata Beauti and the BEAST Cytoscape-web Reference proteome for IEDB VIGOR implementation Planned outreach activities (5 min; Yun Zhang) Scientific conferences Outreach workshop site visits

7 Usage

8 Importance of usage statistics Quantifies value of resource Helps identify issues and opportunities Usage metrics Introduction Web site traffic Workbench accounts Scientific literature citations

9

10 ViPR Website Sessions Audience Overview Nov 4, Nov 7, 2015 Overview 2,000 All Sessions % sessions/wk sessions/wk 58% increase Sessions 1,000 January 2013 July 2013 January 2014 July 2014 January 2015 July 2015 Sessions 129,227 Users 75,605 Pageviews 750,286 New Visitor Returning Visitor 41.7% Pages / Session 5.81 Avg. Session Duration 00:05:45 Bounce Rate 52.60% 58.3% % New Sessions 58.18%

11 Workbench Accounts

12 Scientific Literature Citations 90 Resource Citations Per Year IRD (369 total) ViPR (122 total)

13 Virus Family Popularity Page Pageviews Avg. Time on Page (sec) /brc/home.spg?decorator=filo_ebola /brc/home.spg?decorator=flavi_dengue /brc/home.spg?decorator=flavi /brc/home.spg?decorator=filo /brc/home.spg?decorator=herpes /brc/home.spg?decorator=paramyxo /brc/home.spg?decorator=corona /brc/home.spg?decorator=picorna /brc/home.spg?decorator=flavi_hcv /brc/home.spg?decorator=pox /brc/home.spg?decorator=bunya /brc/home.spg?decorator=toga /brc/home.spg?decorator=calici /brc/home.spg?decorator=rhabdo /brc/home.spg?decorator=reo /brc/home.spg?decorator=arena /brc/home.spg?decorator=hepe Previous year

14 Virus Family Popularity Page Pageviews Avg. Time on Page (sec) /brc/home.spg?decorator=filo_ebola /brc/home.spg?decorator=flavi_dengue /brc/home.spg?decorator=flavi /brc/home.spg?decorator=filo /brc/home.spg?decorator=herpes /brc/home.spg?decorator=paramyxo /brc/home.spg?decorator=corona /brc/home.spg?decorator=picorna /brc/home.spg?decorator=flavi_hcv /brc/home.spg?decorator=pox /brc/home.spg?decorator=bunya /brc/home.spg?decorator=toga /brc/home.spg?decorator=calici /brc/home.spg?decorator=rhabdo /brc/home.spg?decorator=reo /brc/home.spg?decorator=arena /brc/home.spg?decorator=hepe Previous year

15 Paramyxoviridae

16 Flavi Functionality Page Virus Taxa ViPR Functionality Pageviews Avg. Time on Page /brc/home.spg?decorator=flavi_dengue flavi_dengue Home /brc/home.spg?decorator=flavi flavi Home /brc/home.spg?decorator=flavi_hcv flavi_hcv Home /brc/genotyperecombination.spg?method=showcleaninputpage&decorator=flavi_hcv flavi_hcv GenotypeRecombination /brc/workbench_landing.spg?decorator=flavi&method=workbenchdetail flavi Workbench /brc/vipr_genome_search.spg?method=showcleansearch&decorator=flavi_dengue flavi_dengue GenomeSearch /brc/vipr_protein_search.spg?method=showcleansearch&decorator=flavi_dengue flavi_dengue ProteinSearch /brc/vipr_genome_search.spg?method=showcleansearch&decorator=flavi flavi GenomeSearch /brc/blast.spg?method=showcleaninputpage&decorator=flavi_hcv flavi_hcv BLAST /brc/vipr_protein_search.spg?method=showcleansearch&decorator=flavi flavi ProteinSearch /brc/search_landing.spg?decorator=flavi flavi Search /brc/aboutpathogen.spg?decorator=flavi flavi About /brc/search_landing.spg?decorator=flavi_dengue flavi_dengue Search /brc/blast.spg?method=showcleaninputpage&decorator=flavi flavi BLAST /brc/vipr_protein_search.spg?method=showcleansearch&decorator=flavi_hcv flavi_hcv ProteinSearch /brc/genotyperecombination.spg?method=showcleaninputpage&decorator=flavi_dengue flavi_dengue GenotypeRecombination /brc/vipr_genome_search.spg?method=showcleansearch&decorator=flavi_hcv flavi_hcv GenomeSearch /brc/analysis_landing.spg?decorator=flavi flavi Analysis /brc/analysis_landing.spg?decorator=flavi_hcv flavi_hcv Analysis /brc/search_landing.spg?decorator=flavi_hcv flavi_hcv Search /brc/epidatasets.spg?decorator=flavi flavi Epidemiology Datasets /brc/analysis_landing.spg?decorator=flavi_dengue flavi_dengue Analysis /brc/msa.spg?method=showcleaninputpage&decorator=flavi_hcv flavi_hcv MSA /brc/quicktextsearch.spg?method=showquicktextsearch&decorator=flavi flavi QuickSearch /brc/vipr_genome_search.spg?method=submitform&blockid=denguevirus1&decorator=flavi_dengue flavi_dengue GenomeSearch /brc/workbench_landing.spg?decorator=flavi_dengue&method=workbenchdetail flavi_dengue Workbench /brc/staticcontent.spg?decorator=flavi&type=newseventsvipr&subtype=viprmeetingsevents flavi NewsEvents /brc/msa.spg?method=showcleaninputpage&decorator=flavi_dengue flavi_dengue MSA /brc/msa.spg?method=showcleaninputpage&decorator=flavi flavi MSA /brc/workbench_landing.spg?method=workbenchdetail&decorator=flavi flavi Workbench /brc/viprdetails.spg?ncbiproteinid=ach98042&decorator=flavi flavi HCV NS5 protein /brc/vipr_genome_search.spg?method=submitform&blockid=denguevirus2&decorator=flavi_dengue flavi_dengue GenomeSearch /brc/workbench_landing.spg?decorator=flavi_hcv&method=workbenchdetail flavi_hcv Workbench /brc/workbench_landing.spg?method=workbenchdetail&decorator=flavi_hcv flavi_hcv Workbench /brc/quicktextsearch.spg?method=showquicktextsearch&decorator=flavi_dengue flavi_dengue QuickSearch /brc/snpanalysis.spg?method=showcleaninputpage&decorator=flavi flavi SNP /brc/blast.spg?method=showcleaninputpage&decorator=flavi_dengue flavi_dengue BLAST /brc/tree.spg?method=showcleaninputpage&decorator=flavi flavi Tree /brc/vipr_genome_search.spg?method=submitform&blockid=2694&decorator=flavi flavi GenomeSearch /brc/vipr_genome_search.spg?method=submitform&blockid=genotype_1&decorator=flavi_hcv flavi_hcv GenomeSearch /brc/vipr_genome_search.spg?method=submitform&blockid= &decorator=flavi flavi GenomeSearch /brc/vipr_proteinstructure_search.spg?method=showcleansearch&decorator=flavi_dengue flavi_dengue ProteinStructure /brc/vipr_virusepitope_search.spg?method=showcleansearch&decorator=flavi_dengue flavi_dengue Epitope /brc/vipr_genome_search.spg?method=submitform&blockid=denguevirus4&decorator=flavi_dengue flavi_dengue GenomeSearch /brc/episrctypedata.spg?dataset=cases DF+DHS+DSS&typeCvt=1282&decorator=flavi&srcCvt=1304 flavi_dengue Epidemiology Datasets

17 Flavi Functionality Page Virus Taxa ViPR Functionality Pageviews Avg. Time on Page /brc/home.spg?decorator=flavi_dengue flavi_dengue Home /brc/home.spg?decorator=flavi flavi Home /brc/home.spg?decorator=flavi_hcv flavi_hcv Home /brc/genotyperecombination.spg?method=showcleaninputpage&decorator=flavi_hcv flavi_hcv GenotypeRecombination /brc/workbench_landing.spg?decorator=flavi&method=workbenchdetail flavi Workbench /brc/vipr_genome_search.spg?method=showcleansearch&decorator=flavi_dengue flavi_dengue GenomeSearch /brc/vipr_protein_search.spg?method=showcleansearch&decorator=flavi_dengue flavi_dengue ProteinSearch /brc/vipr_genome_search.spg?method=showcleansearch&decorator=flavi flavi GenomeSearch /brc/blast.spg?method=showcleaninputpage&decorator=flavi_hcv flavi_hcv BLAST /brc/vipr_protein_search.spg?method=showcleansearch&decorator=flavi flavi ProteinSearch /brc/search_landing.spg?decorator=flavi flavi Search /brc/aboutpathogen.spg?decorator=flavi flavi About /brc/search_landing.spg?decorator=flavi_dengue flavi_dengue Search /brc/blast.spg?method=showcleaninputpage&decorator=flavi flavi BLAST /brc/vipr_protein_search.spg?method=showcleansearch&decorator=flavi_hcv flavi_hcv ProteinSearch /brc/genotyperecombination.spg?method=showcleaninputpage&decorator=flavi_dengue flavi_dengue GenotypeRecombination /brc/vipr_genome_search.spg?method=showcleansearch&decorator=flavi_hcv flavi_hcv GenomeSearch /brc/analysis_landing.spg?decorator=flavi flavi Analysis /brc/analysis_landing.spg?decorator=flavi_hcv flavi_hcv Analysis /brc/search_landing.spg?decorator=flavi_hcv flavi_hcv Search /brc/epidatasets.spg?decorator=flavi flavi Epidemiology Datasets /brc/analysis_landing.spg?decorator=flavi_dengue flavi_dengue Analysis /brc/msa.spg?method=showcleaninputpage&decorator=flavi_hcv flavi_hcv MSA /brc/quicktextsearch.spg?method=showquicktextsearch&decorator=flavi flavi QuickSearch /brc/vipr_genome_search.spg?method=submitform&blockid=denguevirus1&decorator=flavi_dengue flavi_dengue GenomeSearch /brc/workbench_landing.spg?decorator=flavi_dengue&method=workbenchdetail flavi_dengue Workbench /brc/staticcontent.spg?decorator=flavi&type=newseventsvipr&subtype=viprmeetingsevents flavi NewsEvents /brc/msa.spg?method=showcleaninputpage&decorator=flavi_dengue flavi_dengue MSA /brc/msa.spg?method=showcleaninputpage&decorator=flavi flavi MSA /brc/workbench_landing.spg?method=workbenchdetail&decorator=flavi flavi Workbench /brc/viprdetails.spg?ncbiproteinid=ach98042&decorator=flavi flavi HCV NS5 protein /brc/vipr_genome_search.spg?method=submitform&blockid=denguevirus2&decorator=flavi_dengue flavi_dengue GenomeSearch /brc/workbench_landing.spg?decorator=flavi_hcv&method=workbenchdetail flavi_hcv Workbench /brc/workbench_landing.spg?method=workbenchdetail&decorator=flavi_hcv flavi_hcv Workbench /brc/quicktextsearch.spg?method=showquicktextsearch&decorator=flavi_dengue flavi_dengue QuickSearch /brc/snpanalysis.spg?method=showcleaninputpage&decorator=flavi flavi SNP /brc/blast.spg?method=showcleaninputpage&decorator=flavi_dengue flavi_dengue BLAST /brc/tree.spg?method=showcleaninputpage&decorator=flavi flavi Tree /brc/vipr_genome_search.spg?method=submitform&blockid=2694&decorator=flavi flavi GenomeSearch /brc/vipr_genome_search.spg?method=submitform&blockid=genotype_1&decorator=flavi_hcv flavi_hcv GenomeSearch /brc/vipr_genome_search.spg?method=submitform&blockid= &decorator=flavi flavi GenomeSearch /brc/vipr_proteinstructure_search.spg?method=showcleansearch&decorator=flavi_dengue flavi_dengue ProteinStructure /brc/vipr_virusepitope_search.spg?method=showcleansearch&decorator=flavi_dengue flavi_dengue Epitope /brc/vipr_genome_search.spg?method=submitform&blockid=denguevirus4&decorator=flavi_dengue flavi_dengue GenomeSearch /brc/episrctypedata.spg?dataset=cases DF+DHS+DSS&typeCvt=1282&decorator=flavi&srcCvt=1304 flavi_dengue Epidemiology Datasets

18 Epi Data

19 Overall usage statistics generally look good growth in both citations and website usage Still an opportunity to continue to grow the VIPR user community Challenge in supporting the wide range of virus families that have many independent research communities Specific area of focus: HCV, Paramyxo, Pox Conclusions Host factor component (~300 pageviews/corona; ~3100 total)

20 Recent Enhancements ViPR SWG November 17, 2015

21 Rotavirus A (RVA) Genotyping Reoviridae Loading Virus Pathogen Database and Analysis Resource (ViPR)... About Us Community Announcements Links Resources Support SEARCH DATA ANALYZE & VISUALIZE WORKBENCH SUBMIT DATA VIRUS FAMILIES HELP yun.zhang@jcvi.org Results matching your criteria: 178 SELECT VIRUS(ES) TO INCLUDE IN SEARCH Jump to strain in taxonomy: Start to type strain to get suggestions Species: Rotavirus A Deselect All (14629/14629 strains selected) Deselect All (14629 Strains complete segments) Species: Rotavirus B Select All (0/402 strains selected) (402 Strains complete segments) Species: Rotavirus C Select All (0/816 strains selected) (816 Strains complete segments) Species: Rotavirus D Select All (0/38 strains selected) (38 Strains - 34 complete segments) Species: Rotavirus F Select All COLLECTION YEAR Start: YYYY End: YYYY To add month to search, see Advance Search Options: Month Range GEOGRAPHIC GROUPING All Africa Asia Europe North America Oceania South America COUNTRY Martinique Mexico Nicaragua Panama Puerto Rico Trinidad and Tobago USA HOST SELECTION All Alfalfa Hopper Algae Antelope Arachnid Avian Baboon Bat Bird Blue Crab Bollworm RVA sequences annotated with segment number and genotype Search for RVA sequences by genotype and segment Tool to annotate custom sequences with genotype Browse to and Select Rotavirus A COMPLETE SEQUENCES Complete Sequences Only ROTAVIRUS A-SPECIFIC OPTIONS GENOTYPE G G1 Ex: G1, G3, G% P P[8] Ex: P[2], P[7], P% Mixed Genotype only SEGMENTS All VP1 (R) VP2 (C) VP3 (M) VP4 (P) NSP1 (A) VP6 (I) NSP3 (T) NSP2 (N) VP7 (G) NSP4 (E) NSP5/NSP6 (H) COMPLETE GENOME Complete Genome Set Only ADVANCED OPTIONS Show All Tip: To select multiple or deselect, Ctrl-click (Windows) or Cmd-click (MacOS) Clear Search

22 Coronavirus Ortholog Grouping Mature peptides computed Proteins grouped into ortholog groups based on sequence similarity Search by ortholog group name in Coronaviridae family

23 CiPRES Portal Option to run the analysis in CiPRES Currently available for RaXML Sequences automatically transferred to CiPRES Results are sent back to ViPR and saved to the user s workbench

24 Ebola Portal and D68 Sequence Searches Manually curated clinical outcomes of the 2014 sequences available Quick access to D68 sequences from homepage

25 GO Enrichment Gene enrichment analysis using either Gene Ontology (GO) annotations or Reactome pathway sets Output a list of gene annotation terms or pathways that are enriched in the host factor biosets

26 AWS Cloud Migration To support multi-user tasks To overcome internet bandwidth limitation To conform to new contract limitations in hardware purchases FISMA moderate compatible

27 SWG Feedback

28 Exercises A. Herpesvirus Sequence Search and Sequence Annotation Exploration B. Comparative Genomics Analysis of Dengue Viruses C. Comparative Genomics Analysis of Chikungunya Viruses (CHIKV) D. Host Factor Data Analysis

29 Viral Orthology and Naming Consistency (Herpesviridae)

30 Overview Objectives and Issues The Fire Hose Paraclades Results Drill down Approaches to the naming problem Future work

31 Objectives and Issues Name consistency How do we identify and name functional orthologs? Is our current ortholog clustering software (OrthoMCL) working? If so, what is it doing? How do we quantitatively measure this? Are the loci of different viruses grouping together? If so how? Do some of the ortholog groups span only one species? One genus? One subfamily? An entire family? How do we match up various locus names and find good functional gene names? Define Good.

32 Composite Ortholog Group Table The Fire Hose Search for names by first creating a composite protein table Even in the first 17 rows of GroupID1000 there are inconsistencies. Name Types Current table size for Herpesviridae orthologs is 65,000+ rows The size of the ortholog group table will grow at close to an exponential rate over time.

33 Family-wide statistics have confounded names Ortholog Group 1004 (HHV-1 locus UL28) List of NCBI_Gene_Primary names with counts in brackets Name-count list sorted by count frequency (These prototype web pages are color coded) The names are inconsistent. The names are confounded there is no indication of where the names are coming from or their taxonomic span. The size of this name-count list will grow at a limited ( ~ logarithmic ) rate over the ortholog table size.

34 Paraclades Paraclade A clade minus a branch (or two) Example: Human herpesvirus 1 Reference strain: NC_ Family Paraclade (Herpesviridae) Subfamily Paraclade (Alphaherpesvirinae) Genus Paraclade (Simplexvirus) Species (HHV-1) Name statistics are counted once and only once. Strain (NC_001806)

35 HHV-1 Results Index page Number of Reference Strain and Target Species groups approximately match with the number of HHV-1 loci Indicates the clustering algorithm is working Hyperlinks to locus statistics pages (prototype) Paraclade counts show taxonomic distribution

36 Ortholog groups map well to loci Taxonomic span can be HHV-1, Simplexvirus, Alphaherpesvirinae, or Herpesviridae

37 HHV-1 / UL28 (GroupID 1004) page OK, so what species are these in?

38 HHV-5, Cytomegalovirus

39 Cytomegalovirus (HHV-5) / UL56 page UL56 for HHV-5 is completely disambiguated UL56 and UL28 paraclade positions are now reversed

40 The Protein Naming Problem There are at least 3 dimensions or axes in the name space: Locus Taxa Function It is unlikely that scientists will want to give up the locus names for viral species of interest to them. We can create composite names that concatenate the names along the different axes. For example: <Species>-<LocusName>-<FunctionName> These can be placed in a table of orthologous names

41 Example Name Table All-Taxa counts for GroupID 1004 (HSV1-UL28) Taxonomic Span Protein Name HSV1 VZV CMV KSHV Herpesviridae processing_and_transport_protein UL28 ORF30 UL56 ORF7 SimplexVirus1 envelope-glycoprotein-j US Alphaherpesvirinae capsid_maturation_protease UL26 ORF Betaherpesvirinae envelope_glycoprotein_l - - UL115 - Herpesviridae uracil_dna_glycosylase UL2 ORF59 UL114 ORF46 Gammaherpesvirinae Sushi_domain_SCR_repeat ORF4 Glossary HSV1 Herpes Simplex Virus 1 (Alphaherpesvirinae subfamily) VZV Varicella Zoster Virus (Alphaherpesvirinae) CMV Cytomegalovirus (Betaherpesvirinae) KSHV Kaposi s Sarcoma Herpes Virus (Gammaherpesvirinae)

42 Future Work Create ortholog group statistics for all 14 families Calculate statistics sets for a broad range of target species within each family Clustering algorithms have a variable granularity parameter that adjusts the grouping for more or less distantly related strains. We can now turn this knob and directly observe the effect Test alternative algorithms to OrthoMCL Use GroupID to hyperlink locus names to different target species pages. Assemble a working group to review results

43 ViPR: Enhancing the Host Factor Component to Support Antiviral Research

44 Analysis of Viral Host Factors in ViPR Rationale for inclusion of viral host response analysis into ViPR? - Elucidate key viral mechanisms/pathways - Identify promising host drug targets to yield antiviral effects Host Factor Analysis in ViPR (only Coronaviridae and Orthomyxoviridae) Query: Virus, or Host Factor Boolean Operators Data: Host factor response to viral infection Analysis: Host response patterns in associated biosets Output: Host factors of interest Export Data Enrichment Analysis: -Gene Ontology -Pathways Export Data Future enhancements: - Expand to include additional host factor data and analysis - Integrate with upcoming antiviral drug component in ViPR External Tools: Visualization and Analysis

45 Why are ViPR host factor tools utilized relatively infrequently? Host factor analysis component in ViPR made available March 2012 Host factor analysis component is underutilized. Why? Possible reasons for limited use? -Not interested, or not convinced that host factor data can substantially augment virus research -Not sure how to navigate/utilize host factor toolset -Unfamiliar or uncomfortable with analysis and summarization of large omics data sets -Prefer a different source for virus-host factor information (E.g., VirHostNet 2.0) -Desired functionality or data set not available in ViPR -Other Suggestions or Comments are always appreciated

46 Targeting Host Factors to Treat Hepatitis C High usage of ViPR tools for Hepatitis C virus (HCV) -Response: Implement into ViPR a host factor component specific to needs of HCV researchers Has Hepatitis C already been cured? -Recent direct-acting antivirals (DAAs) cure 80-90% of infected patients -Large number of infected patients non-responsive to DAAs -Emergence of viral strains resistant to even the most promising DAAs -More likely due to high viral mutation rates and short generation times -Tip of the iceberg for DAA resistance An alternative: Drugs that target host factors required for viral infection -Larger number of potential targets -Development of resistance less likely (lower host genetic variability) -Key steps in the HCV life cycle can be targeted -Viral entry -Viral translation -Viral replication -Viral assembly -Release of new virions

47 Hepatitis C Host-Targetting Agents (HTAs) in Development Several HTAs are already in development -Target multiple components of host response -Some FDA approved or in late stage clinical trials Preclinical results combining HTA/DAA are promising -Indicate possible HTA/DAA synergy What can we add to ongoing research through ViPR? o Comprehensive dataset for all host proteins and drugs targeting these proteins relevant to the HCV life cycle o Identify most promising alternative treatments for resistant viral variants o Identify/predict likely efficacious HTA/DAA combinations Zeisel, et. al., Viruses, 2015, 7,

48 Adding Support for Antiviral Drug research in ViPR General Approach: o Incorporate an infrastructure for antiviral drug data and analysis into ViPR o Integrate these data/tools with host factor component of ViPR Overall Goal: o Discovery of host pathways/proteins as potential drug targets to produce antiviral effects - Repurpose previously FDA approved drugs

49 Specific Aim 1: Support for Antiviral Research Compile information on: o Known viral protein targets for all antiviral drugs including drugprotein interaction sites on viral proteins o Antiviral resistance mutations for all viruses supported by ViPR o Implement interface to support access, use, and analysis of these data 86 antiviral drugs: identified from relevant MeSH and ATC codes General Drug Information Drug Name Synonyms ID/Accession Number(s) Drug Categories Type / Group(s) Description Structure: InChi or SMILES Chemical Formula Pharmacology Indication Pharmacodynamics Mechanism of Action Toxicity Affected Organisms Pathways SNP Effects Biointeractions DrugBank Database Target(s) Target Names Protein IDs Gene Organism Pharmacological Action Actions References Drug-Target Interactions Target, virus, virus subtype Drug Chemical Component ID Target-Drug Interaction ID Assay Description IC50, EC50, KI Co-Crystal Structure Specific Amino Acid Binding Site(s) References Known Resistance Mutations* BindingDB Database -Ontology-structured antiviral drug database that can be queried through ViPR -Develop risk assessment tool for emerging viral strains

50 Specific Aim 2: Support for Antiviral Research Compile information on: o Host factor data relevant to viral infection (for all ViPR viruses) o Including transcriptomic, proteomic, RNAi data o Drug targets for all prescription drugs o Modify interface to support pathway and network analysis across all types of omics data Compiled Data: Transcriptomic Pathway RNAi Protein-Protein Interactions Drugs Drug-Targets Drug, Drug-Target Interactome Nodes: Drugs Drug Targets Viruses Pathways Diseases Edges (Interactions): Virus-Protein Protein-Protein Protein-Pathway Drug-Target Drug-Drug

51 Specific Aim 3: Support for Antiviral Research o Represent all system biology data using OpenBEL language o Integrate data into NDEx repository of systems biology data o Develop analysis tools utilizing semantic graph theory methods to navigate integrated pathway and network models o Share tools with other BRCs ViPR Compiled Host Factor Systems Biology Data Convert OpenBEL Semantic Networks Integrate NDEx Repository Using OpenBEL statements to describe experimental data DrugX directly decreases the catalytic activity of ProteinY ß Not Computable can be expressed as: a(chebi:drugx) = cat(hgnc:proteiny) ß Computable! Navigate and Query Analysis: Graph theory algorithms

52 Will these Tools Impact Usage of the Host Factor Component in ViPR? Current Host Factor Analysis in ViPR Data: Host response to infection: Orthomyxoviridae Coronaviridae Analysis: Faceted Search Results/Output: Host response patterns Enriched ontology and pathways Future Implementation Host Factor Analysis in ViPR Data: Host response to virus: All types omics data All supported viruses Analysis: Query Comprehensive Semantic Drug-Target Interactome Results/Output: Host pathways and proteins as drug targets to produce antiviral effects

53 Future Enhancements

54 Enhancements for this contract year Research project driven enhancements Metadata harmonization Analysis tools Annotation Planned enhancements Your enhancement here! We always value community input and prioritize when possible Input from domain experts are critical

55 Research project enhancements Ortholog groups Applying new approach to relevant families Naming Tool Host anti-viral targets RNAi component Cytoscape Web implementation Integration of NDEx Inclusion of public host factor data

56 Metadata harmonization Many viral related metadata standards have been developed in parallel. Examples: CEIRS-DPCC: surveillance, serology, NGS GSCID-BRC: sequence, clinical sequence SysBio-v2.0: host factor data Need to harmonize across standards to improve relational database model

57 Tool enhancements Improved support for user-provided metadata Utilize user provided sequences along with metadata in analysis tools Decorate Phylogenies Perform Metadata-driven Comparative Analysis of uploaded sequences

58 Tool enhancements continued BEAST for advanced phylogenetic analyses Phylogenetic inference, divergence time dating, coalescent analysis, phylogeography Drummond AJ et al Mol Biol Evol BEAUti (model parameters) on ViPR BEAST analysis on CIPRES Relaxed Phylogentic Tree of 69 Influenza A Virus Sequences Drummond AJ (2006) doi:

59 Improved annotation VIGOR Used to annotate viral genomes Web application Genera covered -> Reference Proteome IEDB by request Improve epitope mapping

60 2016 Planned Outreach Activities

61 Scientific Conferences Jan , 2016: Viruses 2016, Basel, Switzerland* Apr , 2016: International Conference on Antivirals Congress, La Jolla, California (Keynote by Dr. Richard Scheuermann) May 1-5, 2016: Positive Strand RNA Viruses, Austin, Texas Jun , 2016: American Society for Virology Annual Meeting, Blacksburg, Virginia* Jul , 2016: International Herpesvirus Workshop, Madison, Wisconsin Aug , 2016: Options for the Control of Influenza, Chicago, Illinois* Dec. 4-8, 2016: Hemorrhagic Fever Viruses (S3), Santa Fe, New Mexico TBD 2016: International Rotavirus Symposium, Melbourne * Exhibit booth

62 Workshop Site Visits 2016 Johns Hopkins University Centers for Disease Control and Prevention Previous workshop site visits Duke-NUS Graduate Medical School, Singapore University of Texas Medical Branch at Galveston Chinese Center for Disease Control and Prevention Institute of Microbiology, Chinese Academy of Sciences Wuhan Institute of Virology, Chinese Academy of Sciences Massachusetts Institute of Technology Harvard University Seattle Biomed International Livestock Research Institute, Kenya University of Rochester Mount Sinai School of Medicine Emory University NIH/NIAID/OCICB University of Pennsylvania Purdue University University of Limpopo, South Africa