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ViPR SWG Meeting
17NOV2015
Introduction and Usage
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
ViPR Development Team
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)
ViPR Advisors
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
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
ViPR SWG Agenda
Usage
Importance of usage statistics – Quantifies value of resource – Helps identify issues and opportunities
Usage metrics – Web site traffic – Workbench accounts – Scientific literature citations
Introduction
www.viprbrc.org
ViPR Website Sessions Go to this report
Nov 4, 2012 - Nov 7, 2015Audience Overview
Language Sessions % Sessions
1. en-us 87,021 67.34%
2. en-gb 5,871 4.54%
3. zh-cn 4,129 3.20%
4. es 3,088 2.39%
5. fr 2,984 2.31%
6. pt-br 2,417 1.87%
7. de 1,968 1.52%
8. es-es 1,736 1.34%
9. en 1,299 1.01%
10. zh-tw 1,299 1.01%
Overview
Sessions
January 2013 July 2013 January 2014 July 2014 January 2015 July 2015
1,0001,0001,000
2,0002,0002,000
Sessions
129,227Users
75,605Pageviews
750,286
Pages / Session
5.81Avg. Session Duration
00:05:45Bounce Rate
52.60%
% New Sessions
58.18%
New Visitor Returning Visitor
41.7%
58.3%
© 2015 Google
All Sessions100.00% 2015 – 1226 sessions/wk
2014 – 772 sessions/wk 58% increase
Workbench Accounts
0
50
100
150
200
250
2008
2009
2010
2011
2012
2013
2014
2015
Scientific Literature Citations
0
10
20
30
40
50
60
70
80
90
2007 2008 2009 2010 2011 2012 2013 2014 2015
Resource Citations Per Year
IRD (369 total) ViPR (122 total)
Page Pageviews Avg. Time on Page (sec) /brc/home.spg?decorator=filo_ebola 4975 99.08 /brc/home.spg?decorator=flavi_dengue 3681 74.79 /brc/home.spg?decorator=flavi 3487 47.27 /brc/home.spg?decorator=filo 2834 54.89 /brc/home.spg?decorator=herpes 2733 54.24 /brc/home.spg?decorator=paramyxo 2589 58.34 /brc/home.spg?decorator=corona 2422 55.31 /brc/home.spg?decorator=picorna 2072 54.29 /brc/home.spg?decorator=flavi_hcv 1905 69.55 /brc/home.spg?decorator=pox 1897 54.55 /brc/home.spg?decorator=bunya 1460 49.96 /brc/home.spg?decorator=toga 1441 45.03 /brc/home.spg?decorator=calici 1321 47.76 /brc/home.spg?decorator=rhabdo 1253 56.60 /brc/home.spg?decorator=reo 1117 48.60 /brc/home.spg?decorator=arena 1071 40.79 /brc/home.spg?decorator=hepe 928 33.88
Virus Family Popularity
Previous year
Page Pageviews Avg. Time on Page (sec) /brc/home.spg?decorator=filo_ebola 4975 99.08 /brc/home.spg?decorator=flavi_dengue 3681 74.79 /brc/home.spg?decorator=flavi 3487 47.27 /brc/home.spg?decorator=filo 2834 54.89 /brc/home.spg?decorator=herpes 2733 54.24 /brc/home.spg?decorator=paramyxo 2589 58.34 /brc/home.spg?decorator=corona 2422 55.31 /brc/home.spg?decorator=picorna 2072 54.29 /brc/home.spg?decorator=flavi_hcv 1905 69.55 /brc/home.spg?decorator=pox 1897 54.55 /brc/home.spg?decorator=bunya 1460 49.96 /brc/home.spg?decorator=toga 1441 45.03 /brc/home.spg?decorator=calici 1321 47.76 /brc/home.spg?decorator=rhabdo 1253 56.60 /brc/home.spg?decorator=reo 1117 48.60 /brc/home.spg?decorator=arena 1071 40.79 /brc/home.spg?decorator=hepe 928 33.88
Virus Family Popularity
Previous year
Paramyxoviridae
Page Virus Taxa ViPR Functionality Pageviews Avg. Time on Page /brc/home.spg?decorator=flavi_dengue flavi_dengue Home 3681 74.79 /brc/home.spg?decorator=flavi flavi Home 3487 47.27 /brc/home.spg?decorator=flavi_hcv flavi_hcv Home 1905 69.55 /brc/genotypeRecombination.spg?method=ShowCleanInputPage&decorator=flavi_hcv flavi_hcv GenotypeRecombination 1550 34.90 /brc/workbench_landing.spg?decorator=flavi&method=WorkbenchDetail flavi Workbench 1146 48.81 /brc/vipr_genome_search.spg?method=ShowCleanSearch&decorator=flavi_dengue flavi_dengue GenomeSearch 1140 92.33 /brc/vipr_protein_search.spg?method=ShowCleanSearch&decorator=flavi_dengue flavi_dengue ProteinSearch 882 80.39 /brc/vipr_genome_search.spg?method=ShowCleanSearch&decorator=flavi flavi GenomeSearch 837 73.22 /brc/blast.spg?method=ShowCleanInputPage&decorator=flavi_hcv flavi_hcv BLAST 775 46.67 /brc/vipr_protein_search.spg?method=ShowCleanSearch&decorator=flavi flavi ProteinSearch 706 77.41 /brc/search_landing.spg?decorator=flavi flavi Search 651 21.87 /brc/aboutPathogen.spg?decorator=flavi flavi About 596 296.75 /brc/search_landing.spg?decorator=flavi_dengue flavi_dengue Search 547 19.62 /brc/blast.spg?method=ShowCleanInputPage&decorator=flavi flavi BLAST 526 52.48 /brc/vipr_protein_search.spg?method=ShowCleanSearch&decorator=flavi_hcv flavi_hcv ProteinSearch 523 79.00 /brc/genotypeRecombination.spg?method=ShowCleanInputPage&decorator=flavi_dengue flavi_dengue GenotypeRecombination 511 23.16 /brc/vipr_genome_search.spg?method=ShowCleanSearch&decorator=flavi_hcv flavi_hcv GenomeSearch 478 69.38 /brc/analysis_landing.spg?decorator=flavi flavi Analysis 442 26.97 /brc/analysis_landing.spg?decorator=flavi_hcv flavi_hcv Analysis 374 22.02 /brc/search_landing.spg?decorator=flavi_hcv flavi_hcv Search 360 16.14 /brc/epiDataSets.spg?decorator=flavi flavi Epidemiology Datasets 336 100.70 /brc/analysis_landing.spg?decorator=flavi_dengue flavi_dengue Analysis 301 27.22 /brc/msa.spg?method=ShowCleanInputPage&decorator=flavi_hcv flavi_hcv MSA 243 65.34 /brc/quickTextSearch.spg?method=showQuickTextSearch&decorator=flavi flavi QuickSearch 242 17.14 /brc/vipr_genome_search.spg?method=SubmitForm&blockId=denguevirus1&decorator=flavi_dengue flavi_dengue GenomeSearch 232 83.07 /brc/workbench_landing.spg?decorator=flavi_dengue&method=WorkbenchDetail flavi_dengue Workbench 229 54.05 /brc/staticContent.spg?decorator=flavi&type=NewsEventsVipr&subtype=viprMeetingsEvents flavi NewsEvents 228 163.58 /brc/msa.spg?method=ShowCleanInputPage&decorator=flavi_dengue flavi_dengue MSA 214 80.72 /brc/msa.spg?method=ShowCleanInputPage&decorator=flavi flavi MSA 213 85.94 /brc/workbench_landing.spg?method=WorkbenchDetail&decorator=flavi flavi Workbench 167 63.71 /brc/viprDetails.spg?ncbiProteinId=ACH98042&decorator=flavi flavi HCV NS5 protein 162 91.66 /brc/vipr_genome_search.spg?method=SubmitForm&blockId=denguevirus2&decorator=flavi_dengue flavi_dengue GenomeSearch 161 82.09 /brc/workbench_landing.spg?decorator=flavi_hcv&method=WorkbenchDetail flavi_hcv Workbench 151 57.42 /brc/workbench_landing.spg?method=WorkbenchDetail&decorator=flavi_hcv flavi_hcv Workbench 140 32.47 /brc/quickTextSearch.spg?method=showQuickTextSearch&decorator=flavi_dengue flavi_dengue QuickSearch 139 19.08 /brc/snpAnalysis.spg?method=ShowCleanInputPage&decorator=flavi flavi SNP 131 113.77 /brc/blast.spg?method=ShowCleanInputPage&decorator=flavi_dengue flavi_dengue BLAST 129 58.68 /brc/tree.spg?method=ShowCleanInputPage&decorator=flavi flavi Tree 127 67.57 /brc/vipr_genome_search.spg?method=SubmitForm&blockId=2694&decorator=flavi flavi GenomeSearch 124 50.39 /brc/vipr_genome_search.spg?method=SubmitForm&blockId=genotype_1&decorator=flavi_hcv flavi_hcv GenomeSearch 117 62.80 /brc/vipr_genome_search.spg?method=SubmitForm&blockId=730-731-732-733-734-735-736-843-844-845-846-847-848-849-850&decorator=flavi flavi GenomeSearch 113 89.69 /brc/vipr_proteinStructure_search.spg?method=ShowCleanSearch&decorator=flavi_dengue flavi_dengue ProteinStructure 109 70.49 /brc/vipr_virusEpitope_search.spg?method=ShowCleanSearch&decorator=flavi_dengue flavi_dengue Epitope 107 73.22 /brc/vipr_genome_search.spg?method=SubmitForm&blockId=denguevirus4&decorator=flavi_dengue flavi_dengue GenomeSearch 102 64.83 /brc/epiSrcTypeData.spg?dataSet=Cases DF+DHS+DSS&typeCvt=1282&decorator=flavi&srcCvt=1304 flavi_dengue Epidemiology Datasets 101 96.22
Flavi Functionality
Page Virus Taxa ViPR Functionality Pageviews Avg. Time on Page /brc/home.spg?decorator=flavi_dengue flavi_dengue Home 3681 74.79 /brc/home.spg?decorator=flavi flavi Home 3487 47.27 /brc/home.spg?decorator=flavi_hcv flavi_hcv Home 1905 69.55 /brc/genotypeRecombination.spg?method=ShowCleanInputPage&decorator=flavi_hcv flavi_hcv GenotypeRecombination 1550 34.90 /brc/workbench_landing.spg?decorator=flavi&method=WorkbenchDetail flavi Workbench 1146 48.81 /brc/vipr_genome_search.spg?method=ShowCleanSearch&decorator=flavi_dengue flavi_dengue GenomeSearch 1140 92.33 /brc/vipr_protein_search.spg?method=ShowCleanSearch&decorator=flavi_dengue flavi_dengue ProteinSearch 882 80.39 /brc/vipr_genome_search.spg?method=ShowCleanSearch&decorator=flavi flavi GenomeSearch 837 73.22 /brc/blast.spg?method=ShowCleanInputPage&decorator=flavi_hcv flavi_hcv BLAST 775 46.67 /brc/vipr_protein_search.spg?method=ShowCleanSearch&decorator=flavi flavi ProteinSearch 706 77.41 /brc/search_landing.spg?decorator=flavi flavi Search 651 21.87 /brc/aboutPathogen.spg?decorator=flavi flavi About 596 296.75 /brc/search_landing.spg?decorator=flavi_dengue flavi_dengue Search 547 19.62 /brc/blast.spg?method=ShowCleanInputPage&decorator=flavi flavi BLAST 526 52.48 /brc/vipr_protein_search.spg?method=ShowCleanSearch&decorator=flavi_hcv flavi_hcv ProteinSearch 523 79.00 /brc/genotypeRecombination.spg?method=ShowCleanInputPage&decorator=flavi_dengue flavi_dengue GenotypeRecombination 511 23.16 /brc/vipr_genome_search.spg?method=ShowCleanSearch&decorator=flavi_hcv flavi_hcv GenomeSearch 478 69.38 /brc/analysis_landing.spg?decorator=flavi flavi Analysis 442 26.97 /brc/analysis_landing.spg?decorator=flavi_hcv flavi_hcv Analysis 374 22.02 /brc/search_landing.spg?decorator=flavi_hcv flavi_hcv Search 360 16.14 /brc/epiDataSets.spg?decorator=flavi flavi Epidemiology Datasets 336 100.70 /brc/analysis_landing.spg?decorator=flavi_dengue flavi_dengue Analysis 301 27.22 /brc/msa.spg?method=ShowCleanInputPage&decorator=flavi_hcv flavi_hcv MSA 243 65.34 /brc/quickTextSearch.spg?method=showQuickTextSearch&decorator=flavi flavi QuickSearch 242 17.14 /brc/vipr_genome_search.spg?method=SubmitForm&blockId=denguevirus1&decorator=flavi_dengue flavi_dengue GenomeSearch 232 83.07 /brc/workbench_landing.spg?decorator=flavi_dengue&method=WorkbenchDetail flavi_dengue Workbench 229 54.05 /brc/staticContent.spg?decorator=flavi&type=NewsEventsVipr&subtype=viprMeetingsEvents flavi NewsEvents 228 163.58 /brc/msa.spg?method=ShowCleanInputPage&decorator=flavi_dengue flavi_dengue MSA 214 80.72 /brc/msa.spg?method=ShowCleanInputPage&decorator=flavi flavi MSA 213 85.94 /brc/workbench_landing.spg?method=WorkbenchDetail&decorator=flavi flavi Workbench 167 63.71 /brc/viprDetails.spg?ncbiProteinId=ACH98042&decorator=flavi flavi HCV NS5 protein 162 91.66 /brc/vipr_genome_search.spg?method=SubmitForm&blockId=denguevirus2&decorator=flavi_dengue flavi_dengue GenomeSearch 161 82.09 /brc/workbench_landing.spg?decorator=flavi_hcv&method=WorkbenchDetail flavi_hcv Workbench 151 57.42 /brc/workbench_landing.spg?method=WorkbenchDetail&decorator=flavi_hcv flavi_hcv Workbench 140 32.47 /brc/quickTextSearch.spg?method=showQuickTextSearch&decorator=flavi_dengue flavi_dengue QuickSearch 139 19.08 /brc/snpAnalysis.spg?method=ShowCleanInputPage&decorator=flavi flavi SNP 131 113.77 /brc/blast.spg?method=ShowCleanInputPage&decorator=flavi_dengue flavi_dengue BLAST 129 58.68 /brc/tree.spg?method=ShowCleanInputPage&decorator=flavi flavi Tree 127 67.57 /brc/vipr_genome_search.spg?method=SubmitForm&blockId=2694&decorator=flavi flavi GenomeSearch 124 50.39 /brc/vipr_genome_search.spg?method=SubmitForm&blockId=genotype_1&decorator=flavi_hcv flavi_hcv GenomeSearch 117 62.80 /brc/vipr_genome_search.spg?method=SubmitForm&blockId=730-731-732-733-734-735-736-843-844-845-846-847-848-849-850&decorator=flavi flavi GenomeSearch 113 89.69 /brc/vipr_proteinStructure_search.spg?method=ShowCleanSearch&decorator=flavi_dengue flavi_dengue ProteinStructure 109 70.49 /brc/vipr_virusEpitope_search.spg?method=ShowCleanSearch&decorator=flavi_dengue flavi_dengue Epitope 107 73.22 /brc/vipr_genome_search.spg?method=SubmitForm&blockId=denguevirus4&decorator=flavi_dengue flavi_dengue GenomeSearch 102 64.83 /brc/epiSrcTypeData.spg?dataSet=Cases DF+DHS+DSS&typeCvt=1282&decorator=flavi&srcCvt=1304 flavi_dengue Epidemiology Datasets 101 96.22
Flavi Functionality
Epi Data
• 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
– Host factor component (~300 pageviews/corona; ~3100 total)
Conclusions
ViPR SWG November 17, 2015
Recent Enhancements
• RVA sequences annotated with segment number and genotype
• Search for RVA sequences by genotype and segment
• Tool to annotate custom sequences with genotype
Rotavirus A (RVA) Genotyping 10/1/2015 Virus Pathogen Database and Analysis Resource (ViPR) - Reoviridae - Genome Search
http://www.viprbrc.org/brc/vipr_genome_search.spg?method=ShowCleanSearch&decorator=reo 1/1
Loading Virus Pathogen Database and Analysis Resource (ViPR)...
Release Date: Sep 10, 2015
This project is funded by the National Institute of Allergy and Infectious Diseases (NIH / DHHS) under Contract No. HHSN272201400028C and is a collaboration between NorthropGrumman Health IT, J. Craig Venter Institute, and Vecna Technologies. Virus images courtesy of CDC Public Health Image Library, Wellcome Images, U.S. Department of VeteransAffairs, Science of the Invisible and ViralZone, Swiss Institute of Bioinformatics.
Start to type strain to get suggestions Deselect All
SELECT VIRUS(ES) TO INCLUDE IN SEARCHJump to strain in taxonomy:
Browse to and Select Rotavirus A
COMPLETE SEQUENCES Complete Sequences Only
Start: YYYY
End: YYYY
COLLECTIONYEAR
To add month tosearch, see AdvanceSearch Options:Month Range
GEOGRAPHIC GROUPING
COUNTRY
HOST SELECTION
GENOTYPEG G1Ex: G1, G3, G%
P P[8]Ex: P[2], P[7], P%
Mixed Genotype only
SEGMENTS COMPLETE GENOME Complete Genome Set Only
ADVANCED OPTIONSSearchClear
Results matching your criteria: 178
ROTAVIRUS A-SPECIFIC OPTIONS
Tip: To select multiple or deselect, Ctrl-click (Windows) or Cmd-click (MacOS)
Show All
Species: Rotavirus A Deselect All(14629/14629 strains selected)
(14629 Strains - 22848 complete segments)
Species: Rotavirus B Select All(0/402 strains selected) (402 Strains - 477 complete segments)
Species: Rotavirus C Select All(0/816 strains selected) (816 Strains - 982 complete segments)
Species: Rotavirus D Select All(0/38 strains selected) (38 Strains - 34 complete segments)
Species: Rotavirus F Select All
AllAfricaAsiaEuropeNorth AmericaOceaniaSouth America
MartiniqueMexicoNicaraguaPanamaPuerto RicoTrinidad and TobagoUSA
AllAlfalfa HopperAlgaeAntelopeArachnidAvianBaboonBatBirdBlue CrabBollworm
AllVP1 (R)VP2 (C)VP3 (M)VP4 (P)NSP1 (A)VP6 (I)NSP3 (T)NSP2 (N)VP7 (G)NSP4 (E)NSP5/NSP6 (H)
Genome Search Search for virus genomic sequences and related information. You can search for the whole virus family or search for specified genus, species etc. You can also find your strainor genome record if you have its information, such as strain name, accession.
Rotavirus A (RVA) the major rotavirus group that infects humans, remains a major cause of morbidity in infants and children worldwide. Given the public health significance,ViPR has introduced dedicated options for searching RVA genomes. Make a selection in the taxonomy browser that includes RVA or check the Rotavirus A checkbox foundbelow the browser.
ViPR Home Reoviridae Home Genome Search
SEARCH DATA ANALYZE & VISUALIZE WORKBENCH SUBMIT DATA VIRUS FAMILIES HELP [email protected]
ReoviridaeAbout Us Community Announcements Links Resources Support
10/1/2015 Virus Pathogen Database and Analysis Resource (ViPR) - Reoviridae - Genome Search
http://www.viprbrc.org/brc/vipr_genome_search.spg?method=ShowCleanSearch&decorator=reo 1/1
Loading Virus Pathogen Database and Analysis Resource (ViPR)...
Release Date: Sep 10, 2015
This project is funded by the National Institute of Allergy and Infectious Diseases (NIH / DHHS) under Contract No. HHSN272201400028C and is a collaboration between NorthropGrumman Health IT, J. Craig Venter Institute, and Vecna Technologies. Virus images courtesy of CDC Public Health Image Library, Wellcome Images, U.S. Department of VeteransAffairs, Science of the Invisible and ViralZone, Swiss Institute of Bioinformatics.
Start to type strain to get suggestions Deselect All
SELECT VIRUS(ES) TO INCLUDE IN SEARCHJump to strain in taxonomy:
Browse to and Select Rotavirus A
COMPLETE SEQUENCES Complete Sequences Only
Start: YYYY
End: YYYY
COLLECTIONYEAR
To add month tosearch, see AdvanceSearch Options:Month Range
GEOGRAPHIC GROUPING
COUNTRY
HOST SELECTION
GENOTYPEG G1Ex: G1, G3, G%
P P[8]Ex: P[2], P[7], P%
Mixed Genotype only
SEGMENTS COMPLETE GENOME Complete Genome Set Only
ADVANCED OPTIONSSearchClear
Results matching your criteria: 178
ROTAVIRUS A-SPECIFIC OPTIONS
Tip: To select multiple or deselect, Ctrl-click (Windows) or Cmd-click (MacOS)
Show All
Species: Rotavirus A Deselect All(14629/14629 strains selected)
(14629 Strains - 22848 complete segments)
Species: Rotavirus B Select All(0/402 strains selected) (402 Strains - 477 complete segments)
Species: Rotavirus C Select All(0/816 strains selected) (816 Strains - 982 complete segments)
Species: Rotavirus D Select All(0/38 strains selected) (38 Strains - 34 complete segments)
Species: Rotavirus F Select All
AllAfricaAsiaEuropeNorth AmericaOceaniaSouth America
MartiniqueMexicoNicaraguaPanamaPuerto RicoTrinidad and TobagoUSA
AllAlfalfa HopperAlgaeAntelopeArachnidAvianBaboonBatBirdBlue CrabBollworm
AllVP1 (R)VP2 (C)VP3 (M)VP4 (P)NSP1 (A)VP6 (I)NSP3 (T)NSP2 (N)VP7 (G)NSP4 (E)NSP5/NSP6 (H)
Genome Search Search for virus genomic sequences and related information. You can search for the whole virus family or search for specified genus, species etc. You can also find your strainor genome record if you have its information, such as strain name, accession.
Rotavirus A (RVA) the major rotavirus group that infects humans, remains a major cause of morbidity in infants and children worldwide. Given the public health significance,ViPR has introduced dedicated options for searching RVA genomes. Make a selection in the taxonomy browser that includes RVA or check the Rotavirus A checkbox foundbelow the browser.
ViPR Home Reoviridae Home Genome Search
SEARCH DATA ANALYZE & VISUALIZE WORKBENCH SUBMIT DATA VIRUS FAMILIES HELP [email protected]
ReoviridaeAbout Us Community Announcements Links Resources Support
• Mature peptides computed • Proteins grouped into ortholog groups based on sequence similarity • Search by ortholog group name in Coronaviridae family
Coronavirus Ortholog Grouping
• 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
CiPRES Portal
• Manually curated clinical outcomes of the 2014 sequences available
Ebola Portal and D68 Sequence Searches
• Quick access to D68 sequences from homepage
• 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
GO Enrichment
• To support multi-user tasks • To overcome internet bandwidth limitation • To conform to new contract limitations in hardware purchases • FISMA moderate compatible
AWS Cloud Migration
SWG Feedback
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
Exercises
Viral Orthology and Naming Consistency���(Herpesviridae)
Objectives and Issues The Fire Hose Paraclades Results Drill down Approaches to the naming problem Future work
Overview
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.
Objectives and Issues
Search for names by first creating a composite protein table – Even in the first 17 rows of GroupID1000 there are inconsistencies. 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.
Composite Ortholog Group Table��� – The Fire Hose
“Name Types”
Ortholog Group 1004 (HHV-1 locus UL28) List of NCBI_Gene_Primary names with counts in brackets
Family-wide statistics have confounded names
• 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.
Paraclades Paraclade ≡ A clade minus a branch (or two) Name statistics are counted once and only once.
Example: Human herpesvirus 1 Reference strain: NC_001806
Family Paraclade (Herpesviridae)
Species (HHV-1)
Strain (NC_001806)
Subfamily Paraclade (Alphaherpesvirinae)
Genus Paraclade (Simplexvirus)
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
Ortholog groups map well to loci
…
Taxonomic span can be HHV-1, Simplexvirus, Alphaherpesvirinae, or Herpesviridae
HHV-1 / UL28 (GroupID 1004) page
OK, so what species are these in?
HHV-5, Cytomegalovirus
…
Cytomegalovirus (HHV-5) / UL56 page
UL56 and UL28 paraclade positions are now reversed
UL56 for HHV-5 is completely disambiguated
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
Example Name Table All-Taxa counts for GroupID 1004 (HSV1-UL28)
Glossary HSV1 Herpes Simplex Virus 1 (Alphaherpesvirinae subfamily) VZV Varicella Zoster Virus (Alphaherpesvirinae) CMV Cytomegalovirus (Betaherpesvirinae) KSHV Kaposi’s Sarcoma Herpes Virus (Gammaherpesvirinae)
Taxonomic Span Protein Name HSV1 VZV CMV KSHV
Herpesviridae processing_and_transport_protein UL28 ORF30 UL56 ORF7
SimplexVirus1 envelope-glycoprotein-J US5 - - -
Alphaherpesvirinae capsid_maturation_protease UL26 ORF33 - -
Betaherpesvirinae envelope_glycoprotein_L - - UL115 -
Herpesviridae uracil_DNA_glycosylase UL2 ORF59 UL114 ORF46
Gammaherpesvirinae Sushi_domain_SCR_repeat - - - ORF4
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
ViPR: Enhancing the Host Factor���Component to Support Antiviral Research
Rationale for inclusion of viral host response analysis into ViPR?
- Elucidate key viral mechanisms/pathways
- Identify promising host drug targets to yield antiviral effects
Analysis of Viral Host Factors in ViPR
Future enhancements: - Expand to include additional host factor data and analysis - Integrate with upcoming antiviral drug component in ViPR
Analysis: Host response patterns in associated biosets
Output: Host factors of interest
Boolean Operators
Enrichment Analysis: -Gene Ontology -Pathways
External Tools: Visualization and Analysis
Export Data Export Data
Query: Virus, or Host Factor
Data: Host factor response to viral infection
Host Factor Analysis in ViPR (only Coronaviridae and Orthomyxoviridae)
Suggestions or Comments are always appreciated
Why are ViPR host factor tools utilized relatively infrequently?
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
Host factor analysis component in ViPR made available March 2012
Host factor analysis component is underutilized. Why?
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
Hepatitis C Host-Targetting Agents (HTAs) in Development
Zeisel, et. al., Viruses, 2015, 7, 5659-5685
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
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
Adding Support for Antiviral Drug research in ViPR
Compile information on: o Known viral protein targets for all antiviral drugs including drug-protein 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
Specific Aim 1: Support for Antiviral Research
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
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*
DrugBank Database BindingDB Database
-Ontology-structured antiviral drug database that can be queried through ViPR
-Develop “risk assessment” tool for emerging viral strains
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
Specific Aim 2: Support for Antiviral Research
Drug, Drug-Target Interactome Nodes: Drugs Drug Targets Viruses Pathways Diseases
Edges (Interactions): Virus-Protein Protein-Protein Protein-Pathway Drug-Target Drug-Drug
Compiled Data:
Transcriptomic Pathway RNAi Protein-Protein Interactions Drugs Drug-Targets
Semantic Networks
Compiled Host Factor Systems Biology Data
Convert OpenBEL
Integrate
ViPR NDEx Repository
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
Specific Aim 3: Support for Antiviral Research
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!
Analysis: Graph theory algorithms
Navigate and Query
Will these Tools Impact Usage of the Host Factor Component in ViPR?
Future Implementation Host Factor Analysis in ViPR
Data:
Host response to virus:
All types –omics data
All supported viruses
Results/Output: Host pathways and proteins as drug targets to produce antiviral effects
Current Host Factor Analysis in ViPR
Data:
Host response to infection: Orthomyxoviridae Coronaviridae
Results/Output:
Host response patterns
Enriched ontology and pathways Faceted Search
Analysis:
Query Comprehensive Semantic Drug-Target Interactome
Analysis:
Future Enhancements
Enhancements for this contract year 2015- 2016 – Research project driven enhancements – Metadata harmonization
– Analysis tools – Annotation
Your enhancement here! – We always value community input and prioritize
when possible – Input from domain experts are critical
Planned 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
Research project enhancements
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
Metadata harmonization
• 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
Tool enhancements
• BEAST for advanced phylogenetic analyses • “Phylogenetic inference,
divergence time dating, coalescent analysis, phylogeography…”
– Drummond AJ et al Mol Biol Evol. 2012
• BEAUti (model parameters) on ViPR
• BEAST analysis on CIPRES
Tool enhancements continued
Drummond AJ (2006) doi:10.1371
Relaxed Phylogentic Tree of 69 Influenza A Virus Sequences
• VIGOR • Used to annotate viral genomes • Web application • Genera covered ->
• Reference Proteome • IEDB by request • Improve epitope mapping
Improved annotation
2016 Planned Outreach Activities
Jan. 26-28, 2016: Viruses 2016, Basel, Switzerland*
Apr. 17-21, 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. 18-22, 2016: American Society for Virology Annual Meeting, Blacksburg, Virginia*
Jul. 23-27, 2016: International Herpesvirus Workshop, Madison, Wisconsin
Aug. 24-28, 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
Scientific Conferences
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
Workshop Site Visits 2016 Johns Hopkins University Centers for Disease Control and Prevention Previous workshop site visits
