Virus Pathogen Resource (ViPR) September 2016 New … · novel Antiviral Resistance Risk Assessment...

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New Enterovirus portal! Sifting through viral data below the family level can be a challenge. The launch of the new Enterovirus portal makes it easy to search, retrieve, and analyze enterovirus data based on virus species and type such as enterovirus A71, human poliovirus 1/2/3, enterovirus D68, etc. Here you can: • access integrated data: sequence data, experimentally determined epitopes, 3D protein structures, curated antiviral drug data, and derived data, including mature peptide predictions, generated by ViPR computational pipelines. • use a suite of analysis tools: multiple sequence alignment, phylogenetic tree construction and visualization, metadata- driven comparative analysis, sequence variation analysis, antiviral resistance risk assessment, BLAST, short peptide search, PCR primer design, genome annotation, etc. • store and share data through your personal Workbench Enterovirus data summary as of Sept. 29, 2016 Antiviral Drug Data Analysis Antiviral Drug SFVT/PVT A new focus area of ViPR development is to provide comprehensive support for antiviral drug data analysis. Following the curation of antiviral drug data related to viruses supported in IRD and ViPR, we have added these data to our Sequence Feature Variant Type infrastructure. Specifically, each drug binding site or antiviral resistance mutation is defined as a Sequence Feature (SF). For each SF, all protein sequences in IRD/ViPR are grouped into Variant Types, defined by the unique sequence variations within the defined SF region. In the case of antiviral resistance mutation SFs, we have predicted whether a virus strain is likely to be drug resistant using our existing Phenotypic Variant Type (PVT) computational pipeline. This new feature facilitates sequence-based predictions of virus responses to antiviral drug treatment. Summary of antiviral drug Sequence Features Antiviral Resistance Risk Assessment In order to allow users to predict whether a viral strain is potentially sensitive or resistant to an antiviral drug, we have developed a novel Antiviral Resistance Risk Assessment tool, which annotates user-provided sequences with curated antiviral drug data. This tool is available for Hepatitis C Virus, Picornaviridae, and Herpesviridae. Simply visit “Analyze & Visualize” and select “Antiviral Resistance Risk Assessment”. New Host Factor Data Through collaboration with the NIH/NIAID Systems Biology Centers for Infectious Disease Research and IRD/ViPR-led mining of publically available data, we have added seven new datasets on host responses to viral infection, including influenza virus (A/ PR/8/34) and SARS-CoV. The Host Factor Data component in IRD/ViPR not only facilitates data retrieval, but also supports the comparison of host responses under different experimental and infection conditions including gene set enrichment analysis. Antiviral Resistance Risk Assessment tool detects antiviral mutations in user-provided sequences. This particular human herpesvirus 1 strain carries the R176W PVT of Human herpesvirus 1_Thymidine Kinase_antiviral-response_176(1), which confers increased resistance to Acyclovir. Recent Publications • Zhang, Y, et al. (2016) Influenza Research Database: An integrated bioinformatics resource for influenza virus research. Nucl. Acids Res. PMID: 27679478 This article highlights the recent enhancements in IRD. Outreach Events October 9-15, 2016: 3rd Annual Short Course for emerging leaders in Medical Virology of the Global Virus Network, University of Maryland, Baltimore. We will teach a bioinformatics workshop. October 24-25, 2016: 8th International Global Virus Network Meeting, Sapporo, Japan. We will give a talk on the identification of Zika diagnostic peptides using ViPR data and analysis resources. Enterovirus Virion: non-enveloped, spherical with a diameter of about 30 nm Genome: positive-sense, single-stranded RNA genome of 7.2-8.5 kb, composed of a long and highly structured 5’-noncoding region and a single ORF Proteome: 11 mature peptides Infection: initiates by attaching to a cellular receptor, for example, CD155 as a poliovirus receptor RNA Transcript: 5’-noncoding region linked to a viral protein (VPg), 3’ poly-A tail Transmission: fecal-oral and respiratory transmission Phylogeny: 12 distinct virus species identified, including Enterovirus A-J and Rhinovirus A-C Epidemiology: worldwide; 5-10 million symptomatic infections per year in the US Clinical: causes a spectrum of distinct syndromes. PV: poliomyelitis; rhinovirus: common cold; CV: asceptic meningitis and encephalitis, paralysis, hand-foot-and-mouth disease (A10, A16), upper respiratory illness, hepatitis, acute hemorrhagic conjunctivitis (CVA24), cardiac disease (CVB); EV-D68: lower respiratory illness; EV-D70: acute hemorrhagic conjunctivitis, paralysis; EV-A71: hand-foot-and-mouth disease, meningoencephalitis, paralysis Reference: David M. Knipe, Peter M. Howley, et al. Fields’ Virology. 5th ed. 2007. Lippincott Williams & Wilkins, USA Structure: poliovirus 1 Mahoney, PMID 2994218, PDB 2PLV, rendered by J.Y. Sgro using GRASP (PMID 1758883) Schematics: ViralZone - Enterovirus Search Search our comprehensive database for: Analyze Analyze data online: Save to Workbench Use your workbench to: Browse All Search Types Browse All Tools Genomes Genes & proteins Sequence Feature Variant Types Immune epitopes 3D protein structures Host Factor Data Antiviral Drugs Sequence Alignment Phylogenetic Tree Sequence Variation (SNP) Metadata-driven Sequence Analysis Genome Annotator BLAST Store and share data Combine working sets Integrate your data with ViPR data Store and share analyses Custom search alert SEARCH DATA ANALYZE & VISUALIZE WORKBENCH VIRUS FAMILIES HELP [email protected] Enterovirus About Us Community Announcements Links Resources Support A portion of the Enterovirus portal landing page Category Total Species 490 Strains 57,618 3D Protein Structures (PDB) 268 Experimentally Determined Epitopes (IEDB) 1,532 Genomes with Clinical Metadata (NIAID GSCID, manual curation) 134 Mature Peptides 7,364 Sequence Features with Variant Types 8 Proteins with Predicted Epitopes 130,792 Total Genomes 64,481 Complete Genomes 2,259 Proteins 165,360 Virus Drug Resistance Drug Binding Site Enterovirus 2 6 Hepatitis C virus 21 10 Herpesvirus 243 5 Parainfluenza virus 1 Influenza virus 38 59 Virus protein: thymidine kinase NCBI Reference Sequence: AEQ77053.1 Organism: Human herpesvirus 1 Download Results gb:ADM52181|gi:30538: 56 Antiviral resistance mutation sequence feature variants in this sequence Antiviral Resistance Risk Details This page displays query results identifying the presence of antiviral resistance mutations in user uploaded sequences. Users may download resistance mutation sequence feature details (MS Excel) for a specific or all uploaded sequences by clicking the corresponding download results button. Expand All / Collapse All Reference Sequence Antiviral Resistance Mutations in User Sequence MASYPCHQHA SAFDQAARSR GHSNRRTALR PRRQQEATEV RLEQKMPTLL RV YI D H GM K TT TTQLLV ALGSRDDIVY 080 VP PMT YW RV LGASETIANI YT Q HRLDQG EISAGDAAVV MTSA QIT M GM PYAVTDAV LA PHI GGEAGSS HAPPPALTLI 160 D RHPI AAL L C Y A WY LMG SMTP QA VL AF VALIPPTLP G TNI VL G LPE DRHID RLAK R Q RPGER LDLA MLAAIRRV YG 240 LLAN TVRYLQ CGGSWREDWG QLSGTAVTPQ GAEPQSNAGP RPHIGD TLFT LFRAPEL LAP NGDLYNVFAW ALDV LAKRLR 320 PMHVFILDYD QSPAG CRDAL LQLTSGMVQT HVTTPGSIPT ICD LARTFAR EMGEAN 376 Human herpesvirus 1_Thymidine Kinase_antiviral- response_176(1) VT-4 5 176 R 176 W Increased Resistance to Acyclovir Gaudreau A, Hill E, Balfour HH, Jr., Erice A, Boivin G. Phenotypic and genotypic characterization of acyclovir- resistant her- pes simplex viruses from immunocompro- mised patients. Journal of Infectious Diseases 1998; 178: 297–303. Chibo D, Druce J, Sasadeusz J, Birch C. Molecular analysis of clinical isolates of acyclovir resistant herpes simplex virus. Antiviral Research 2004; 61: 83–91. Kussmann-Gerber S, Kuonen ViPR Home Herpesviridae Home Antiviral Resistance Risk Assessment Results Results Details Types Amino Acid in Reference Sequence Amino Acid in User Sequence Phenotype(s) in User Sequence Literature Cited SEARCH DATA ANALYZE & VISUALIZE WORKBENCH VIRUS FAMILIES HELP yun.zhang@jcv Herpesviridae About Us Community Announcements Links Resources Support September 2016 New Features in ViPR Virus Pathogen Resource (ViPR) Questions? Problems? Suggestions? Click Here

Transcript of Virus Pathogen Resource (ViPR) September 2016 New … · novel Antiviral Resistance Risk Assessment...

New Enterovirus portal!Sifting through viral data below the family level can be a challenge. The launch of the new Enterovirus portal makes it easy to search, retrieve, and analyze enterovirus data based on virus species and type such as enterovirus A71, human poliovirus 1/2/3, enterovirus D68, etc.

Here you can:

• access integrated data: sequence data, experimentally determined epitopes, 3D protein structures, curated antiviral drug data, and derived data, including mature peptide predictions, generated by ViPR computational pipelines.

• use a suite of analysis tools: multiple sequence alignment, phylogenetic tree construction and visualization, metadata-driven comparative analysis, sequence variation analysis, antiviral resistance risk assessment, BLAST, short peptide search, PCR primer design, genome annotation, etc.

• store and share data through your personal Workbench

Enterovirus data summary as of Sept. 29, 2016

Antiviral Drug Data AnalysisAntiviral Drug SFVT/PVT

A new focus area of ViPR development is to provide comprehensive support for antiviral drug data analysis. Following the curation of antiviral drug data related to viruses supported in IRD and ViPR, we have added these data to our Sequence Feature Variant Type infrastructure. Specifically, each drug binding site or antiviral resistance mutation is defined as a Sequence Feature (SF). For each SF, all protein sequences in IRD/ViPR are grouped into Variant Types, defined by the unique sequence variations within the defined SF region. In the case of antiviral resistance mutation SFs, we have predicted whether a virus strain is likely to be drug resistant using our existing Phenotypic Variant Type (PVT) computational pipeline. This new feature facilitates sequence-based predictions of virus responses to antiviral drug treatment.

Summary of antiviral drug Sequence Features

Antiviral Resistance Risk Assessment

In order to allow users to predict whether a viral strain is potentially sensitive or resistant to an antiviral drug, we have developed a novel Antiviral Resistance Risk Assessment tool, which annotates user-provided sequences with curated antiviral drug data. This tool is available for Hepatitis C Virus, Picornaviridae, and Herpesviridae. Simply visit “Analyze & Visualize” and select “Antiviral Resistance Risk Assessment”.

New Host Factor DataThrough collaboration with the NIH/NIAID Systems Biology Centers for Infectious Disease Research and IRD/ViPR-led mining of publically available data, we have added seven new datasets on host responses to viral infection, including influenza virus (A/PR/8/34) and SARS-CoV. The Host Factor Data component in IRD/ViPR not only facilitates data retrieval, but also supports the comparison of host responses under different experimental and infection conditions including gene set enrichment analysis.

Antiviral Resistance Risk Assessment tool detects antiviral mutations in user-provided sequences. This particular human herpesvirus 1 strain carries the R176W PVT of Human herpesvirus 1_Thymidine Kinase_antiviral-response_176(1), which confers increased resistance to Acyclovir.

Recent Publications• Zhang,Y,etal.(2016)Influenza

Research Database: An integrated bioinformatics resource for influenza virus research. Nucl. Acids Res. PMID: 27679478

This article highlights the recent enhancements in IRD.

Outreach Events• October 9-15, 2016: 3rd Annual

Short Course for emerging leaders in Medical Virology of the Global Virus Network, University of Maryland, Baltimore. We will teach a bioinformatics workshop.

• October 24-25, 2016: 8th International Global Virus Network Meeting, Sapporo, Japan. We will give atalkontheidentificationofZikadiagnostic peptides using ViPR data and analysis resources.

Loading Virus Pathogen Database and Analysis Resource (ViPR)...

EnterovirusVirion: non­enveloped, spherical with a diameter of about 30 nmGenome: positive­sense, single­stranded RNA genome of 7.2­8.5 kb, composed of a longand highly structured 5’­noncoding region and a single ORFProteome: 11 mature peptidesInfection: initiates by attaching to a cellular receptor, for example, CD155 as a poliovirusreceptorRNA Transcript: 5’­noncoding region linked to a viral protein (VPg), 3’ poly­A tailTransmission: fecal­oral and respiratory transmissionPhylogeny: 12 distinct virus species identified, including Enterovirus A­J and RhinovirusA­CEpidemiology: worldwide; 5­10 million symptomatic infections per year in the USClinical: causes a spectrum of distinct syndromes. PV: poliomyelitis; rhinovirus: commoncold; CV: asceptic meningitis and encephalitis, paralysis, hand­foot­and­mouth disease(A10, A16), upper respiratory illness, hepatitis, acute hemorrhagic conjunctivitis (CVA24),cardiac disease (CVB); EV­D68: lower respiratory illness; EV­D70: acute hemorrhagicconjunctivitis, paralysis; EV­A71: hand­foot­and­mouth disease, meningoencephalitis,paralysisReference: David M. Knipe, Peter M. Howley, et al. Fields’ Virology. 5th ed. 2007.Lippincott Williams & Wilkins, USA

Structure: poliovirus 1 Mahoney, PMID 2994218, PDB 2PLV, rendered by J.Y.Sgro using GRASP (PMID 1758883)Schematics: ViralZone ­ Enterovirus

SearchSearch our comprehensive database for:

AnalyzeAnalyze data online:

Save to WorkbenchUse your workbench to:

Browse All Search Types Browse All Tools

Data on host response toInfluenza and SARS

infections is now available!Host­virus interaction data produced bylaboratories associated with the NIAID­fundedSystems Biology for Infectious DiseasesResearch Program is now available in ViPR.

This release increases the amount of hostfactor data for a total of 35 microarray, 16proteomics and 4 lipidomics (in vivo and invitro) experiments for various SARS­CoVstrains as well as H5N1 and H1N1 influenzaA viruses.In this release, the capability is nowavailable to search for a single host factoracross multiple experiments through the'Host Factor Results' button on the 'HostFactor Biosets' page. In addition, displayingthe Reactome pathway(s) containing one(or more) host factors are now availablefrom both the 'Patterns' and 'BooleanOperator' pages.Additional experiments using various '­omics' technologies, as well as analyticaland visualization tools will become availablein future releases of ViPR.

For more details about these studies, or to view

Genomes

Genes & proteins

Sequence Feature Variant Types

Immune epitopes

3D protein structures

Host Factor Data

Antiviral Drugs

Sequence Alignment

Phylogenetic Tree

Sequence Variation (SNP)

Metadata­driven Sequence Analysis

Genome Annotator

BLAST

Store and share data

Combine working sets

Integrate your data with ViPR data

Store and share analyses

Custom search alert

Highlights

Mature viral protein products resulting from protease­ andself­cleavage of the polyprotein are displayed according to

Go to Workbench

Video Tutorial Tutorial

ViPR WorkbenchThe ViPR Workbench allows users to save 'working sets'of sequences, searches and analysis results between websessions in their own private workspace. Users can shareworking sets or analysis results with collaborators.

Key Highlights:Save and organize working sets of sequences,analysis results and search criteriaVisualize saved analysis resultsShare working sets and analysis results with othersUpload personal sequences and combine with existing working sets

SEARCH DATA ANALYZE & VISUALIZE WORKBENCH VIRUS FAMILIES HELP [email protected]

EnterovirusAbout Us Community Announcements Links Resources Support

A portion of the Enterovirus portal landing page

Category Total Species 490

Strains 57,618

3D Protein Structures (PDB) 268

Experimentally Determined Epitopes (IEDB) 1,532

Genomes with Clinical Metadata (NIAID GSCID, manual curation) 134

Mature Peptides 7,364

Sequence Features with Variant Types 8

Proteins with Predicted Epitopes 130,792

Total Genomes 64,481

Complete Genomes 2,259

Proteins 165,360 Virus Drug Resistance Drug Binding Site Enterovirus 2 6 Hepatitis C virus 21 10 Herpesvirus 243 5 Parainfluenza virus 1 Influenza virus 38 59

Category Total Species 490

Strains 57,618

3D Protein Structures (PDB) 268

Experimentally Determined Epitopes (IEDB) 1,532

Genomes with Clinical Metadata (NIAID GSCID, manual curation) 134

Mature Peptides 7,364

Sequence Features with Variant Types 8

Proteins with Predicted Epitopes 130,792

Total Genomes 64,481

Complete Genomes 2,259

Proteins 165,360 Virus Drug Resistance Drug Binding Site Enterovirus 2 6 Hepatitis C virus 21 10 Herpesvirus 243 5 Parainfluenza virus 1 Influenza virus 38 59

Loading Virus Pathogen Database and Analysis Resource (ViPR)...

Release Date: Sep 29, 2016

This system is provided for authorized users only. Anyone using this system expressly consents to monitoring while using the system. Improper use of this system may be referred to lawenforcement officials.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.

Virus protein: thymidine kinaseNCBI Reference Sequence: AEQ77053.1Organism: Human herpesvirus 1

Download Results

gb:ADM52181|gi:30538: 56 Antiviral resistance mutation sequence feature variants in this sequence

Download All Results

Antiviral Resistance Risk DetailsThis page displays query results identifying the presence of antiviral resistance mutations in user uploaded sequences. Users may download resistance mutation sequencefeature details (MS Excel) for a specific or all uploaded sequences by clicking the corresponding download results button.

Expand All / Collapse All

Reference Sequence

Antiviral Resistance Mutations in User Sequence

MASYPCHQHA SAFDQAARSR GHSNRRTALR PRRQQEATEV RLEQKMPTLL RVYIDGPHGM GKTTTTQLLV ALGSRDDIVY 080

VPEPMTYWRV LGASETIANI YTTQHRLDQG EISAGDAAVV MTSAQITMGM PYAVTDAVLA PHIGGEAGSS HAPPPALTLI 160

FDRHPIAALL CYPAAWYLMG SMTPQAVLAF VALIPPTLPG TNIVLGALPE DRHIDRLAKR QRPGERLDLA MLAAIRRVYG 240

LLANTVRYLQ CGGSWREDWG QLSGTAVTPQ GAEPQSNAGP RPHIGDTLFT LFRAPELLAP NGDLYNVFAW ALDVLAKRLR 320

PMHVFILDYD QSPAGCRDAL LQLTSGMVQT HVTTPGSIPT ICDLARTFAR EMGEAN 376

resistance to acyclovir: a site­directed mutagenesis study.Antimi­ crobial Agents andChemotherapy 2005; 49:1055–1059.

Humanherpesvirus1_Thymidine

Kinase_antiviral­response_176(1)

VT­4 5 176 R 176 W Increased Resistance to Acyclovir Gaudreau A, Hill E, BalfourHH, Jr., Erice A, Boivin G.Phenotypic and genotypiccharacterization of acyclovir­resistant her­ pes simplexviruses from immunocompro­mised patients. Journal ofInfectious Diseases 1998; 178:297–303. Chibo D, Druce J,Sasadeusz J, Birch C.Molecular analysis of clinicalisolates of acyclovir resistantherpes simplex virus. AntiviralResearch 2004; 61: 83–91. Kussmann­Gerber S, Kuonen

ViPR Home Herpesviridae Home Antiviral Resistance Risk Assessment Results Results Details

SequenceFeature Name

VariantType

NumberofVariantTypes

Position inReferenceSequence

AminoAcid inReferenceSequence

Position inUserSequence

AminoAcid inUserSequence

Phenotype(s) in User Sequence Literature Cited

SEARCH DATA ANALYZE & VISUALIZE WORKBENCH VIRUS FAMILIES HELP [email protected]

HerpesviridaeAbout Us Community Announcements Links Resources Support

September 2016

New Features in ViPR

Virus Pathogen Resource (ViPR)

Questions? Problems? Suggestions?Click Here