Raquel Tobes
Marina Manrique
Eduardo Pareja-Tobes
2013-08-26
Problem definition
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content
• intro
• problem
• background & general concepts
• guidelines
• week plan
• teams
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Problem
Design a system to rapidly
characterize and identify the
pathogen responsible for an
outbreak
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Based on
NGS and
Cloud Computing
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Background & general concepts
• what is an outbreak?
• impact
• outbreaks and NGS
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What is an outbreak?
“Outbreak is a term used
in epidemiology to describe an
occurrence of disease greater
than would otherwise be expected
at a particular time and place.”
Wikipedia
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What is an outbreak?
Normally caused by an infectious
agent
Virus
Bacteria
Fungi
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What is an outbreak?
Healthcare associated
Community acquired
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What is an outbreak?
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What is an outbreak?
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What is an outbreak?
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What is an outbreak?
Antibiotic resistant bugs
High-risk clones
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What is an outbreak?
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What is an outbreak?
Extension:
Really local (ICU)
Worldwide
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What is an outbreak?
Local
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What is an outbreak?
Worldwide
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What is an outbreak?
Worldwide
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Impact
A real impact on public health
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Impact
Avian flu H1N1
CDC estimates
• 61 million people infected with 2009 H1N1
• 274,000 2009 H1N1-related hospitalizations
• 12,470 2009 H1N1-related deaths
http://www.cdc.gov/h1n1flu/estimates_2009_h1n1.htm
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Impact
Multistate Fungal Meningitis Outbreak
Current outbreak in the States
Healthcare associated infection. Non contagious
http://www.cdc.gov/hai/outbreaks/meningitis.html
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Impact
Multistate Fungal Meningitis Outbreak
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Impact
Multistate Fungal Meningitis Outbreak
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Impact
Multistate Fungal Meningitis Outbreak
This is just a real case of how an outbreak is tracked
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Impact
Multistate Fungal Meningitis Outbreak
This is just a real case of how an outbreak is tracked
Where the detection is based on PCR and sequencing
But what if...
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Impact
Multistate Fungal Meningitis Outbreak
-The agent is not well characterized? We don’t have
this set of primers or they don’t work nicely
- The agent is spreading (even) much faster than
expected? We need quicker ways to identify it
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Impact
NGS and Cloud
Computing
could help here?
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Outbreaks and NGS
Quickly characterize the pathogen
and identify it
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Outbreaks and NGS
Quickly characterize the pathogen
and identify it
That’s a fact today
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Outbreaks and NGS
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Outbreaks and NGS
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Outbreaks and NGS
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Outbreaks and NGS
EHEC German outbreak 2011
A real example of how NGS was used for
characterizing the pathogen and designing
primers to detect it
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Outbreaks and NGS
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*
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*
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genomic data available
Detection kit protocol
Outbreaks and NGS
EHEC German outbreak 2011
Detection kit protocols and synthesized primers
available
In 16 days from the announcement of the outbreak
In only 6 days from the release of the first genomic
data
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Outbreaks and NGS
So yes,
NGS may be (and is) useful in this field
in at least to steps:
1. Genome Characterization
2. Pathogen detection
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Outbreaks and NGS
What about Cloud Computing?
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Guidelines
NGS: your design should have an answer for
Rapid characterization of the pathogen causing the outbreak
- How would you characterize the pathogen? De novo assembly
of the genome + annotation? MLST? Searching for virulence
proteins exclusively? All, none?
- How quick you can do it once you have the sequences?
- Your design is scalable?
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Guidelines
NGS: your design should have an answer for
Rapid identification of the pathogen in samples
- You have the agent characterized, how you’d identify it?
- The identification would be based on PCR? Whole
genome sequencing?
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Guidelines
Some general questions you should address in
the design
- Which sequencing technology (or combination of them) would
you use?
- Which samples requirements you would have? Could you work
with clinical samples? really low DNA quantity with poor quality?
Would you need a prior phase of pathogen isolation and growth?
- How long the whole process would take (wet lab + data analysis)?
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Guidelines
The more realistic and detailed the better.
It’s a design and research task.
There’s not a unique correct solution for it
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Week plan
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Teams
Team 1
Kim
Om
Andrea
Habib
Team 2
Fabian
Lizzy
Alexandre
Alexandra
Vedran
Team 3
Alexey
Jeannine
Jasmin
Somya
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Data sets
https://github.com/ehec-outbreak-crowdsource
d/BGI-data-analysis/wiki/Sequence-reads