Lessons Learned from DNA Fingerprinting and Genome Sequencing

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LESSONS LEARNED FROMDNA FINGERPRINTINGAND
GENOME SEQUENCING
dr. jennifer gardy bc centre for disease control
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GENOME SEQUENCING IS ABOUT TO CHANGE THE WAY WE
INVESTIGATE OUTBREAKS OF TUBERCULOSIS.
the main point
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the status quo
a combination of traditional epidemiology and
molecular epidemiology is used to understand
the origins and transmission dynamics of disease
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TRADITIONAL EPIDEMIOLOGY FINDS RELATIONSHIPS
BETWEEN PEOPLE, PLACES, OBJECTS, AND BEHAVIOURS
THAT MAY CONTRIBUTE TO DISEASE SPREAD
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people arent the only things that can be
interviewed
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pathogens can be interviewed too!
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MOLECULAR EPIDEMIOLOGY FINDS PHENOTYPIC OR
GENETIC RELATIONSHIPS BETWEEN ISOLATES THAT
SUGGEST A COMMON SOURCE OF INFECTION
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serotyping
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RFLP/PFGE
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mlst multi-locus sequence typing
mlva multi-locus vntr analysis
AGCTAGTCTATGCGTACGTACGTACGTACGTACGTACGTACGTATAGCTA
GAGAT
AGCTAGTCTATGCGTACGTACGTACGTACGTACGTACGTATAGCTAGAGA
T
AGCTAGTCTATGCGTACGTACGTACGTACGTACGTATAGCTAGAGAT
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TB molecular epidemiology
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SMEARS ON GELS
IS6110 RFLP
spoligotyping
MIRU-VNTR
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INSIGHTS
IDENTIFY CLUSTERS TRANSMISSION RISK
FACTORS STRAIN DISPERSAL LOCAL HISTORY GEOGRAPHY
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ROADBLOCKS
LOW-RESOLUTION TECHNICAL CHALLENGES AFFECTS
INTERPRETATION
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but how can we improve our resolution?
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only 0.03 is used for typing
of a typical TB genome (4.4 million bases)
while the remaining 99.97 is ignored
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if we could look at the other 99.97 - the WHOLE
genome of every isolate in an outbreak
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we could go from a low-res view.
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to a high-resolution one
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HOORAY FOR NEXT-GEN SEQUENCING!
GENOMIC EPIDEMIOLOGY is now fast, cheap, and
accessible to public health
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how to do genomic epidemiology

1. look at all the DNA in every outbreak isolate.
2. find single nucleotide changes (snps).
3. track those snps from person to person.
4. bask in new-found understanding of outbreak.

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This facilitates outbreak reconstruction.
AACCTTGG
TACCTTGG
TACCTTGG
AACCTTGG
AAACTTGG
AAACTTGG
But it doesnt guarantee anything. And its
not as easy as this picture makes it look when
youre dealing with something like TB.
AAACTTGG
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It also provides insight into the biology and
pathogenesis of the organism.
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first TB outbreak reconstruction the long
version
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MAY
2006
adult female.
pleural TB.
RFLP matched earlier cases from the same region.
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JULY
infant female.
TB meningitis.
matching RFLP.
community takes notice
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OCTOBER
by
9
more cases with matching RFLP were diagnosed.
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outbreak reconstruction was impossible using a
traditional approach
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source case
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LESSONS

1. GENOMIC DATA COULD RECONSTRUCT THE OUTBREAK
2. REQUIRED GOOD EPI/CLINICAL DATA
3. SLOW PROCESS
4. REQUIRED UNIQUE EXPERTISE AND COMPUTATIONAL
   RESOURCES

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OPPORTUNITIES

• MORE OUTBREAKS! PATTERNS?
• DISTINGUISH BETWEEN RECENT TRANSMISSION AND
  REACTIVATION?
• IDENTIFY SOURCE CASES, CHARACTERISTICS?
• PERFORM SEQUENCING AT PROVINCIAL TB LAB FOR RAPID
  TURNAROUND

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the big picture
better outbreak/epidemic reconstructions better
understanding of disease dynamics better
control and prevention measures
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BCCDC TB CONTROL BCPHMRL TB LAB VIHA IHA FNIH SIMO
N FRASER UNI. GENOME BC