Databases and tools to study the genomes of hundreds of pathogens, - PowerPoint Presentation

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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)

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A brief history of genomics

ΦX174

5,375

bp

1977

H. influenza

1.8 x 10

6

bp

1995

H. sapiens

3

x 10

9

bp

2001

H. sapiens

3

x 10

9 bpphased

2007

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Sequencing Costs

NGS

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Database resources – human genomics

http://

cancergenome.nih.gov

http://www.

1000genomes.org

http://

genome.ucsc.edu

http://

huref.jcvi.org

http://

www.ncbi.nlm.nih.gov

/SNP/

http://

www.ncbi.nlm.nih.gov

/

clinvar

/

http://

www.knome.com

h

uman

g

enomics

resources

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Database resources – plant genomics

plant

g

enomics

resources

http://

www.plantgdb.org

http://

www.gramene.org

https://

arabidopsis.org

http://

www.jcvi.org

/

cgi

-bin/

medicago/overview.cgi

http://

www.iplantcollaborative.org

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Database resources – human

microbiome

and

metagenomics

www.hmpdacc.org

http://camera.calit2.net

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www.viprbrc.org

www.fludb.org

Database resources

– pathogen genomics

www.patricbrc.org

www.eupathdb.org

www.vectorbase.org

NIAID Bioinformatics Resource Centers (BRCs)

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Research at JCVI

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Infectious Disease

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Viral Genomics

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www.viprbrc.org

www.fludb.org

Database resources

– pathogen genomics

www.patricbrc.org

www.eupathdb.org

www.vectorbase.org

NIAID Bioinformatics Resource Centers (BRCs)

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Zoonosis SummaryA 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

p

estis, Borrelia burgdorferi, Plasmodium knowlesi.Use of comparative genomics to understand zoonotic spillover – what are the genetic determinants that allow an animal virus to adapt to human

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H7N9 use caseIn 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?

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Virus pathogen genomics – IRD

www.fludb.org

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H7N9 human HA query

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H7N9 human HA query result

1

2

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H7N9 human HA query result

1

2

3

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H7N9 human HA query result

1

2

3

4

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Phylogenetic analysisPhyML

in IRD

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Sequence alignment

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Statistical comparative genomics

Meta-CATS in IRD

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Sequence features affected

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Sequence features affected

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3D structure

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H7N9 and JCVINew isolate sequencingPublic release of sequence dataData – Analysis – Visualization - IntegrationComparative genomics analysisSynthetic genomics of vaccine seed strains

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JCVI Core CompetenciesHuman, microbial, and plant genomicsMicrobiome and metagenomicsSynthetic genomicsData management, analysis, and miningNovel computational methods developmentInformatics infrastructure developmentWeb applications

High performance computing

Cloud computing