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Rob Niche Dimensions Edwards What would you do with hundreds of - - PowerPoint PPT Presentation

Oct 23, 2023 372 likes •1.07k views

UNAM The Global Evolution and 2012 Adaptation of Vibrio cholerae Across Multiple Rob Niche Dimensions Edwards What would you do with hundreds of genome sequences? Cholerae Haiti Global evolution Niche dimensions What's

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The Global Evolution and Adaptation of Vibrio cholerae Across Multiple Niche Dimensions

Rob Edwards

UNAM 2012

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What would you do with hundreds

  • f genome sequences?
  • Cholerae
  • Haiti
  • Global evolution
  • Niche dimensions
  • What's important
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Cholera is caused by Vibrio cholerae

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A world wide pandemic

About 3-5 million cases per year About 100 - 200,000 deaths world wide per year Notable deaths:

  • Tchaikovsky
  • Polk (11th President USA)
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Symptoms

About 75% of patients have no symptoms 25-50 PINTS of diarrhea per DAY Severe symptoms are by dehydration Treatment Clean water Electrolytes Vaccine Not antibiotics

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Multiple Pandemics

1st – 1817 to 1823 Started at the Ganges, spread by colonialists 2nd – 1829 to 1849 Worldwide spread via immigrants 3rd – 1852 to 1859 John Snow first epidemiologist

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First epidemiological study

John Snow Portrait painted in 1847 when he was 34 years

  • ld.
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First epidemiological study

John Snow Cholera outbreak in Soho, London 1854 Plotted all cases on a map Found big cluster around water well

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John Snow’s Map

First epidemiological study

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On the mode of communication of Cholera 1854

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Cholera caused by bacteria Outbreaks of cholera

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Multiple Pandemics

1st – 1817 to 1823 Started at the Ganges, spread by colonialists 2nd – 1829 to 1849 Worldwide spread via immigrants 3rd – 1852 to 1859 John Snow first epidemiologist 4th – 1863 to 1879 Originated in mecca 5th – 1881 to 1896 First cholerae vaccine (1892) 6th – 1899 to 1923 Killed 800,000 people 7th – 1961 to present

  • 1991: South America killed > 100,000 people
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Haitian Outbreak

Earthquake Jan 12th, 2010 No cholera in Haiti for > 50 years First case, October 22nd, 2010 By February, 2011 250,000 cases and ~5,000 deaths What was the original source?

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Haitian cholera outbreaks

http://www.ph.ucla.edu/

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Source: Final Report of the Independent Panel of Experts on the Cholera Outbreak in Haiti

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Cases by day – Mirebalais Hospital

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Cases by Age – St Marc Hospital

On October 20th, 2010

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Haitian Outbreak

Two hypotheses: Endemic, waterborne strain that has been in Haiti but not caused disease for 50 years Imported from another country

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The environmental hypothesis

"They have been fortunate in Haiti that for 50 years the conditions have been such that they haven’t had an intense increase in cholera bacterial populations. ... But they’ve had an earthquake, they’ve had destruction, they’ve had a hurricane ... I think it’s very unfortunate to look for a scapegoat. It is an environmental phenomenon that is involved”

Rita Colwell Johns Hopkins School of Public Health

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The human hypothesis

“The organism that is causing the disease is very uncharacteristic of (Haiti and the Caribbean), and is quite characteristic of the region from where the soldiers in the base came. ... I don't see there is any way to avoid the conclusion that an unfortunate and presumably accidental introduction of the organism occurred."

John Mekalanos Harvard Medical School

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Conditions favor human hypothesis

Source: Final Report of the Independent Panel of Experts on the Cholera Outbreak in Haiti

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Conditions favor human hypothesis

Source: Final Report of the Independent Panel of Experts on the Cholera Outbreak in Haiti

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Conditions favor human hypothesis

Source: Final Report of the Independent Panel of Experts on the Cholera Outbreak in Haiti

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Cholerae Mimicus Parahemolyticus Harveyi Vibrio cholerae from Bangladesh in 1994 Vibrio cholerae from Haiti in 2010 Vibrio cholerae from Bangladesh in 2002 Vibrio cholerae from Haiti in 2010 Vibrio cholerae from Haiti in 2010

On the source of Haitian cholera

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Nepalese soldiers?

Outbreak in Khatmandu, Nepal before the soldiers left Outbreaks downstream (not upstream) along the river from the nepalese UN camp But that could have come from river trade. Ships used to fly the yellow flag when they were quarantined by cholera

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Haitian cholera outbreaks

http://www.ph.ucla.edu/

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Global evolution of Vibrio

Can we use genomics to identify the global evolution of Vibrio? Which gene(s) are important for temporal/spatial variation?

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Prototype Vibrio cholerae sequence

TIGR Nature 406, 477-483(3 August 2000)

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Sequenced genomes

2011 – 32 Vibrio strains sequenced

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Fabiano Thompson's Lab @ UFRJ

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Fundação Oswaldo Cruz

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Ion quality scores

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Sequenced genomes

2011 – 32 Vibrio strains sequenced 2011 – 171 Vibrio strains sequenced

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Reads per chromosome (Chr. I)

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Reads per chromosome (Chr. I)

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Cholera Toxin Phage

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Annotated using RAST

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Merge frameshifts

  • Merge adjacent genes if:
  • Have the same function
  • Have similarity to the same 3rd party protein
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Frameshift frequency

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Metabolic reconstruction considers the pathways present in the cell Based on comparison to Sanger sequenced V. cholerae El Tor strain (a virulent pathogen)

Is it any good?

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R-18304 (Ion) El T

  • r

(Sanger)

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R-18304 (Ion) El T

  • r

(Sanger)

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Single nucleotide polymorphisms

ATCATCGATCAGCATGCATCAGCATCGATCAGC ATCATCGATCAGCATGCATCAGCATCGATCAGC ATCATCGATCAGCATGCATCAGCCTCGATCAGC ATCATCGATCAGCATGCATCAGCCTCGATCAGC ATCATCGATCAGCAAGCATCAGCCTCGATCAGC ATCATCGATCAGCAAGCATCAGCCTCGATCAGC ATCATCGATCAGCAAGCATCAGCCTCGATCAGC ATCATCGATCAGCAAGCATCAGCCTCGAGCAGC ATCATCGATCAGCAAGCATCAGCCTCGAGCAGC

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Global evolution

Mutreja et al 2011

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Waves of spread of cholera

Mutreja et al 2011

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Different evolution for each wave

Mutreja et al 2011

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Cholerae Mimicus Parahemolyticus Harveyi Vibrio cholerae from Bangladesh in 1994 Vibrio cholerae from Haiti in 2010 Vibrio cholerae from Bangladesh in 2002 Vibrio cholerae from Haiti in 2010 Vibrio cholerae from Haiti in 2010

On the source of Haitian cholera

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Evolution not only by SNPs

Conservation of the ~120 kb superintegron region across 210 strains

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Horizontal gene transfer versus Vertical evolution

Mother Daughter Daughter

S N P s HGT

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Niche dimensions

  • 210 Vibrio genomes
  • Reassembled
  • Reannotated
  • Find interesting

genes!

  • Year
  • Continent
  • Country
  • Lat/Lon Coordinates
  • Clinical or Environmental
  • Source
  • Serogroup
  • Serotype
  • Biotype
  • Mutreja wave
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Serogroup

  • V. cholerae classification

Vibrio cholerae Non-cholera toxin No disease Cholera toxin O1 O139 Classical El Tor Ogawa Inaba Epidemics

Biotype Serotype

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Niche dimensions

  • 210 Vibrio genomes
  • Reassembled
  • Reannotated
  • Find interesting

genes!

  • Year
  • Continent
  • Country
  • Lat/Lon Coordinates
  • Clinical or Environmental
  • Source
  • Serogroup
  • Serotype
  • Biotype
  • Mutreja wave
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Response variables

  • 15,000 genes in the pangenome
  • 933 subsystems (pathways) present in at least
  • ne genome
  • SNPs (after Mutreja)
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Analysis

  • Recreate evolution of the Vibrios
  • What are the important genes for each niche

dimension

Who, what, when, where! Use random forests to identify important variables

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Random Forest

O-antigen Exopoly- saccharide Capsule Sialic Acid DNA recomb. 01 10 20 5 10 01 10 20 5 10 01 10 20 5 10 0139 100 1 8 10 0139 100 1 8 10 0139 100 1 8 10 0139 100 1 8 10

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O139 O1 Exopoly- saccharide

<50

Random Forest

O1 O139 DNA- recombination

10

O1 O139 Capsule

<10

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Random Forest

Each tree votes on the importance

  • f each

variable. Typically, run 10,000 trees

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Genes important for who ? (serogroup)

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Genes important for what? (clinical, environmental, ...)

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Genes important for where? (continent)

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Separation of functions by continent

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Genes important for when? (year)

DNA Repair

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DNA repair & phages

Normal DNA repair (134 strains) umuC umuD Additional DNA repair (4 strains; not O1) umuC umuD Phage borne DNA repair (72 strains) umuC prophage

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Different evolution for each wave

Mutreja et al 2011 Waves 2 & 3 have phage Interrupted repair

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Conclusions

  • Unraveling evolution and spread of new

pathogens

  • Mining genomes and niche dimensions
  • Don't get scooped!
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Discussion points

  • What is the value of multi genome projects?
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Current multigenome projects

Organism Number Organism Number

  • S. pyogenes

3,615 Mycobacterium tuberculosis 390

  • S. pneumoniae

3,085 Salmonella in cattle and humans 373 Rice (Oryza sativa) 3,000 Vibrio 274

  • C. elegans

2,007 Shigella sonnei 263 Clostridium difficile 1,250 Mycobacterium tuberculosis 259 The thousand (human) genome project 1,092 Streptococcus pneumoniae 240 Mycobacterium tuberculosis 1,000 Methicillin-resistant Staphylococcus aereus 193 Plasmodium falciparum 825 Campylobacter jejuni 192 Streptococcus pneumoniae 616 Mycobacterium abscessus in CF 170 Nick Loman: http://lab.loman.net/