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Yun Zhang J. Craig Venter Institute June 23, 2014

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  1. Sequence Variation Identification and Functional/Structural Inference in the Influenza Research Database (IRD) and Virus Pathogen Resource (ViPR) Yun Zhang J. Craig Venter Institute June 23, 2014

  2. Challenges for Sequence Analysis Sequence Variation Identification Functional/Structural Inference • Manual analysis • Data amount • Subjective • Novel analysis tool • Statistical • Genotype-phenotype correlation • Sequence Feature (SF) • Curated from literature, public archives, direct submission • 2,747 influenza SFs, 543 Dengue SFs, 301 HCV SFs, 296 Vaccinia SFs Clin Infect Dis. (2013) 57 (4): 622-624 Influenza virus A_NS1_nuclear-export-signal_137(11) Buried in literature http://www.library.ucsf.edu/node/2337

  3. www.fludb.org www.viprbrc.org

  4. Sequence Variation Analysis Workflow Influenza A_ H3_ experimentally- determined-epitope_156(7)

  5. Use Case: Influenza H7N9 Virus • 2013 Influenza virus A H7N9 outbreak • H7 viruses have historically circulated in birds and horses • H7N9 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?

  6. Sequence Search – H7N9 HA & Similar Sequences 1. H7N9 HA complete sequences 2. HA sequences highly similar to a typical H7N9 human strain

  7. Meta-CATS Analysis – Grouping similar older H7 sequences H7N9 outbreak HA sequences vs. similar older H7 sequences H7N9 human HA sequences

  8. Meta-CATS Analysis Results

  9. Verify Results on Alignment 235L/I H7N9 human strains Older H7 avian strains

  10. Meta-CATS Analysis Results

  11. Variant Position Mapped to Sequence Features 2 161

  12. Variant Positions Visualized on Protein Structure Variant position 235 Ligands 4BSC: H7N9 HA in Complex with 6'-SLN

  13. Summary A novel sequence variation identification and functional/structural inference workflow www.viprbrc.org www.fludb.org

  14. Acknowledgments Northrop Grumman Scott Stuart, Program Manager Ed Klem, Ph.D., Project Manager ZhipingGu, Ph.D. Sherry He WenjieHua Wei Jen Sanjeev Kumar Xiaomei Li, Ph.D. Jason Lucas Bruce Quesenberry Barbara Rotchford Tom Smith, Ph.D. Hongbo Su, Ph.D. Bryan Walters Sam Zaremba, Ph.D. Hongtao Zhao, Ph.D. Liwei Zhou, Ph.D. • NIAID / DMID • Alison 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 Officer J. Craig Venter Institute Richard Scheuermann (PI) Brian Aevermann, M.S. Douglas Greer, Ph.D. Brett Pickett, Ph.D. Rick Stanton, M.S.E.E Lucy Stewart, MBA Yun Zhang, M.Sc. Vecna Chris Larsen, Ph.D. Al Ramsey, Ph.D. Guangyu Sun, Ph.D. LANL Catherine Macken, Ph.D. Mira Dimitrijevic Southern Methodist Univ Monnie McGee, Ph.D. Mengya Liu, Ph.D. NIAID HHSN272200900041C