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Research Talk- 3/9/15

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Elisa Margolis

on 9 March 2016

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Transcript of Research Talk- 3/9/15

Cure for Microbiome Mania
Causality:
Ellie Margolis
ways to do
studies?
Cross- Convergent Mapping Example
unique low pH of vaginal niche
who's responsible?
Bacterial Vaginosis:
daily sampled vaginal microbiome
Cross- Convergent Mapping:
community function mechanisms
vaginal Microbiome & pH
often attributed to Lactobacillus competitive exclusion
Cross Convergent Mapping
Sample
DNA extraction
species specific
broad
range
sort
classify
classify
antibiotics?
infection
that triggered
antibiotics?
Or
normal flora
constantly shifting
species reacting to
changes in environment & other species
or
premise: cause precedes effect
Cross Convergent Mapping
provides testable hypotheses to causality
questions with all types of microbiome data
can distinguish who is responsible for a community function with fine resolution
can provide greater confidence in distinguishing interactions from similar response to environment
Seattle Children's Hospital
Fred Hutchinson Cancer
PIDS St Jude Research Fellowship Award
pediatric infectious disease fellowship
David Fredricks

Tina Fielder
Congzhou Liu
Nette Oot

Andrew Wiser
Erin de la Cruz
synchrony
spurious
correlations
environmental
forcing
species
interactions
shared noise (sampling)
problems with current method
correlation Based
Thanks
why do we need better causality tools?
Kissing: microbial detector for partner compatibility
Tetro CBC Fresh Air
Microbiome Mania
1) describe diversity
how does science slips into hype...
poor resolution &
unreproducible composition
3) cure the disease
by modifying microbiome
2) attribute variance
problem: there is no gold standard
our solution:
simulate data
Test common microbiome pipelines
simulations: no error & no novel species
how do I know if I've adequately described what's in my sample?
HMP
our
normals
target
composition
read depth
our
normals
relative frequency
(each genus
sampled by log function )
in-silico PCR
full length 16S rRNA
novel read generation
error introduced
observation
problem:
tons possible stories
combination increases recurrence after treatment
accepted story: produces biofilms that shields
new hypotheses: interacts metabolically, influences susceptibility or shields
54 Malawi infant gut microbiomes
sampled every 2 months

Malnutrition- weight-for-height z score
What components of the microbiome are responsible for growth (prevent or recover from malnutrition)?
Cross- Convergent Mapping:
Community Function Resolution
Cross- Convergent Mapping:
from NYtimes
Jonathan Golob
useful screen to spur science that can live up to all the hype
New Yorker
bad
good
bad
good
probiotics
antibiotics
phage therapy
microbiome transpant
Inability to detect causality
simulated communities
True
Qiime:
pplacer
pplacer
True
Qiime:
closed
Qiime:
de novo
closed
de novo
cluster
97% similar
align to eachother
classify
compare to database:
RDP
reference
condensed
dataset of 97% OTU:
greengenes
classify
compare each to reference:
take top hit
discard no hits
reference tree
build based on seq
recruit sparse branches
classify
bayseian probability
tree placement
vaginal microbiome interactions from same 44 women
distinguish environmental forcing from interactions
Cross- Convergent Mapping:
distinguish environmental forcing from interactions
special thanks to Jeremiah Davis for ccm illustration
Cross Convergent Mapping
premise: cause precedes effect
see if historical events
account for effects in another
time
0
1
2
3
4
0
1
2
3
Cross Convergent Mapping
premise: cause precedes effect
see if historical events
account for effects in another
time
0
1
2
3
4
1-lag
2-lag
3-lag
Cross Convergent Mapping
premise: cause precedes effect
see if historical events
account for effects in another
time
0
1
2
3
4
1-lag
2-lag
3-lag
Cross Convergent Mapping
premise: cause precedes effect
see if historical events
account for effects in another
time
0
1
2
3
4
developed by Matsen
no antibiotics
metronidazole
Funding
sugihara et al. Science. 2012
(distance standard deviation
WHO Child Growth Standards)
Limitations: may be inappropriate for some relative frequency types of data, requires sufficient dynamics for each mirobe, pairwise interaction
C. difficile in Infants
contribution of infant microbiome & developing immune system to benign colonization
single infanT Colonized by Multiple C. Difficile over course of 1st year
CCM: screen interactions
Test interactions infant hamster C. diff model
lack of colitis may not just be due to receptors
no disturbance
disturbance
reciprocal
unilateral
Full transcript