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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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