Sequence Variation Identification and Functional/Structural Inference in the Influenza Research Database (IRD) and Virus Pathogen Resource (ViPR)

Sequence Variation Identification and Functional/Structural Inference in the Influenza Research Database (IRD) and Virus Pathogen Resource (ViPR) Yun ZhangJ. Craig Venter InstituteJune 23, 2014Challenges for Sequence AnalysisSequence Variation Identification

Functional/Structural Inference

Influenza virus A_NS1_nuclear-export-signal_137(11)Sequence Feature (SF) Curated from literature, public archives, direct submission2,747 influenza SFs, 543 Dengue SFs, 301 HCV SFs, 296 Vaccinia SFs

Clin Infect Dis. (2013) 57 (4): 622-624Manual analysisData amountSubjectiveNovel analysis toolStatisticalGenotype-phenotype correlation

http://www.library.ucsf.edu/node/2337

Buried in literature2

www.fludb.org

www.viprbrc.orgSequence Variation Analysis Workflow

Influenza A_ H3_ experimentally- determined-epitope_156(7)

4Use Case: Influenza H7N9 Virus2013 Influenza virus A H7N9 outbreakH7 viruses have historically circulated in birds and horsesH7N9 human cases: 1st human case reported in March 2013, 410 human cases as of April 2014, fatality rate 22%

Sequence variations involved in human adaptation?5Sequence Search H7N9 HA & Similar Sequences

2. HA sequences highly similar to a typical H7N9 human strain1. H7N9 HA complete sequences 6Meta-CATS Analysis Grouping

similar older H7 sequences H7N9 human HA sequences

H7N9 outbreak HA sequences vs. similar older H7 sequences 7Meta-CATS Analysis Results

Verify Results on Alignment

Older H7 avian strainsH7N9 human strains235L/I9Meta-CATS Analysis Results

Variant Position Mapped to Sequence Features161211Variant Positions Visualized on Protein StructureVariant position 235Ligands4BSC: H7N9 HA in Complex with 6'-SLN

Human H7N9 Influenza Virus Haemagglutinin (with Asn-133 Glycosylation) in Complex with Human Receptor Analogue 6'-SLN12SummaryA novel sequence variation identification and functional/structural inference workflow

www.viprbrc.org

www.fludb.orgFree you from the time-consuming process 13Acknowledgments NIAIDHHSN272200900041CJ. Craig Venter InstituteRichard Scheuermann (PI)Brian Aevermann, M.S.Douglas Greer, Ph.D.Brett Pickett, Ph.D.Rick Stanton, M.S.E.ELucy Stewart, MBAYun Zhang, M.Sc.

VecnaChris Larsen, Ph.D.Al Ramsey, Ph.D.Guangyu Sun, Ph.D.

LANLCatherine Macken, Ph.D.Mira Dimitrijevic

Southern Methodist UnivMonnie McGee, Ph.D.Mengya Liu, Ph.D.Northrop GrummanScott Stuart, Program ManagerEd Klem, Ph.D., Project ManagerZhiping Gu, Ph.D.Sherry HeWenjie HuaWei JenSanjeev KumarXiaomei Li, Ph.D.Jason LucasBruce QuesenberryBarbara RotchfordTom Smith, Ph.D.Hongbo Su, Ph.D.Bryan WaltersSam Zaremba, Ph.D.Hongtao Zhao, Ph.D.Liwei Zhou, Ph.D.

NIAID / DMIDAlison Yao, Ph.D., Contracting Officer Representative, Microbial Genomics & Advanced Technologies

Andrei Gabrielian, Ph.D., Office of Cyber Infrastructure and Computational Biology

Diane Post, Ph.D., CEIRS Project Officer14