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SCH Resident/Fellow Research Day

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Elisa Margolis

on 15 October 2015

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Transcript of SCH Resident/Fellow Research Day

Isolate day-day fluctations
L. jensenii
Research into the turnover of the 3 trillion bacteria that live on us


Microbiome Techniques
Focus in on one site
Preliminary Data
Understanding Microbiome Dynamics
<1 sec of being germ-free
Elisa Margolis MD PhD

preterm
influence labor
& neonatal infections
protect against
pathogens
otitis
train immune
system
asthma
metabolic
profile
obesity
tractable populations
earliest influence
ease of sampling
fewer species
positive controls for species interactions
Focus in on one methodology
vaginal microbiome
-demographic process (birth, death, migration)
-interactions (competition, immune, host, metabolites)
-noise/error (sampling, PCR sensitivity)
David Fredricks Laboratory
adopted from New Yorker 2012

what process produces these fluctuations?
Identify Species Interactions
This technique may be applicable to different sites, methods & questions
If we know how the addition or subtraction of one particular species effects others....
we can determine which intervention has the greatest likelihood of success
longitudinal sampling
Sample
DNA extraction
& qPCR
Thanks
Seattle Children's Hospital Infectious Disease
PIDS/St Jude Research Fellowship
David Fredricks
Members of the lab
correlations close to 1.0 could indicate species + interact Or just that both species like the same environment
one step further: evidence that one of these species' improves the forecast (predictive causality) of another species' time series
subject b
subject a:
(Null Hypothesis)
Chung et al. Cell, 2012; 149(7): 1578-93
Ley RE et al. Obesity alters gut microbial ecology. PNAS 2005; 102:11070–11075
Hyman et al. Reproductive Sci 2014; 21(1): 32-40
Pettigrew et al. Appl Envrion Microbiol 2012; 78(17):6262-70
broad
range
sort
classify
sort
classify
qPCR
meta
16S NGS
qPCR
16S NGS
metagenome
species specific
L. jensenii
L crispatus / L jensenii
null hypothesis
F statistic
P value
L crispatus Granger-cause L jensenii
0.001
0.981
L jensenii Granger-cause L crispatus
0.208
0.650
L iners / G vaginalis
null hypothesis
F statistic
P value
L iners Granger-cause G vaginalis
0.293
0.747
G vaginalis Granger-cause L iners
8.433
0.005
How can we modify our
patient's microbiomes?

Nuanced methods will require knowing interactions
C
Current Methods:
Antibiotics
Fecal Transplant
qPCR
# copies
Validation:
multiple subjects
multivariable analysis
lab competition assays
Full transcript