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Databases and tools to study the genomes of hundreds of pathogens, plants, and mammals

Databases and tools to study the genomes of hundreds of pathogens, plants, and mammals. Richard H. Scheuermann, Ph.D. Director of Informatics J. Craig Venter Institute (JCVI). A brief history of genomics. H. sapiens 3 x 10 9 bp phased. ΦX174 5,375 bp. H. influenza 1.8 x 10 6 bp.

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Databases and tools to study the genomes of hundreds of pathogens, plants, and mammals

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  1. Databases and tools to study the genomes of hundreds of pathogens, plants, and mammals Richard H. Scheuermann, Ph.D. Director of Informatics J. Craig Venter Institute (JCVI)

  2. A brief history of genomics H. sapiens 3 x 109bp phased ΦX174 5,375 bp H. influenza 1.8 x 106bp H. sapiens 3 x 109bp 1977 1995 2001 2007

  3. Sequencing Costs NGS

  4. Database resources – human genomics http://huref.jcvi.org http://genome.ucsc.edu human genomics resources http://www.ncbi.nlm.nih.gov/clinvar/ http://cancergenome.nih.gov http://www.1000genomes.org http://www.ncbi.nlm.nih.gov/SNP/ http://www.knome.com

  5. Database resources – plant genomics http://www.gramene.org plant genomics resources http://www.jcvi.org/cgi-bin/medicago/overview.cgi http://www.plantgdb.org https://arabidopsis.org http://www.iplantcollaborative.org

  6. Database resources – human microbiome and metagenomics www.hmpdacc.org http://camera.calit2.net

  7. Database resources – pathogen genomics www.vectorbase.org www.eupathdb.org www.patricbrc.org www.viprbrc.org www.fludb.org NIAID Bioinformatics Resource Centers (BRCs)

  8. Research at JCVI

  9. Infectious Disease

  10. Viral Genomics

  11. Database resources – pathogen genomics www.vectorbase.org www.eupathdb.org www.patricbrc.org www.viprbrc.org www.fludb.org NIAID Bioinformatics Resource Centers (BRCs)

  12. Zoonosis Summary • A zoonosis is an infectious disease that is transmitted between species (sometimes by a vector) from animals other than humans to humans or from humans to other animals. • Of the 1415 recognized species of human pathogens, 61% are of zoonotic origin [Taylor 2001]. • These include Hendra, Nipah, Machupo, Ebola, Influenza A, SARS-CoV, Yersinia pestis, Borreliaburgdorferi, Plasmodium knowlesi. • Use of comparative genomics to understand zoonotic spillover – what are the genetic determinants that allow an animal virus to adapt to human

  13. H7N9 use case • In February and March 2013, several human cases of influenza virus A H7N9 subtype were identified in Shanghai, China and surrounding provinces. • As of August 12, 2013, a total of 135 human cases have been laboratory confirmed, including 44 deaths for a case fatality rate of 33%. • A search for H7 influenza strains in IRD (data accessed from www.fludb.org on April 8, 2013) returned a total of 1485 strains, with 1306 from birds, 102 from environmental samples (usually bird droppings), 33 from horses and only 17 from humans prior to the recent outbreak. • Of the 17 human H7 isolates, 12 were H7N7 from England 1996 and the Netherlands 2003. None were H7N9. • Questions – • Where is the reservoir source of this newly emerging human pathogen? • What are the genetic determinants allowing for human adaptation?

  14. Virus pathogen genomics – IRD www.fludb.org

  15. H7N9 human HA query

  16. H7N9 human HA query result 1 2

  17. H7N9 human HA query result 1 2 3

  18. H7N9 human HA query result 1 2 3 4

  19. Phylogenetic analysis PhyML in IRD

  20. Sequence alignment

  21. Statistical comparative genomics Meta-CATS in IRD

  22. Sequence features affected

  23. Sequence features affected

  24. 3D structure

  25. H7N9 and JCVI • New isolate sequencing • Public release of sequence data • Data – Analysis – Visualization - Integration • Comparative genomics analysis • Synthetic genomics of vaccine seed strains

  26. JCVI Core Competencies • Human, microbial, and plant genomics • Microbiome and metagenomics • Synthetic genomics • Data management, analysis, and mining • Novel computational methods development • Informatics infrastructure development • Web applications • High performance computing • Cloud computing

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