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Lab Meeting

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by

Elisa Margolis

on 3 March 2016

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Transcript of Lab Meeting

Microbiome Causality
Ellie Margolis
ways to do
studies?
Cross- Convergent Mapping Example I
unique low pH of vaginal niche
whose responsible?
Bacterial Vaginosis:
combination of A. vaginae & G. vaginalis increases recurrence after treatment
daily sampled vaginal microbiome
Cross- Convergent Mapping Example II
Metronidazole
No antibiotics
vaginal microbiome interactions from same 44 women
dark grey:
reciprocal interactions
Cross- Convergent Mapping Example III
vaginal Microbiome & pH
often attributed to Lactobacillus competitive exclusion
X(t)
X(t+lag)
X(t+2lag)
Time
Abundance of Species X
(or relative abundance)
lag
2 x lag
If so than prior values of that species predict whats going to happen to the other species (X-->Y).
Is there convergence?
Do the nearest neighbors of one species (X) map correspond to nearest neighbors in another species (Y)?
Alternative:Cross Convergent Mapping
Can independently ask about Y --> X, as the nearest neighbors in Y map may not correspond to nearest neighbors in X.
Sample
DNA extraction
species specific
broad
range
sort
classify
classify
what causes this?
antibiotics?
infection
that triggered
antibiotics?
Or
normal flora
constantly shifting
species reacting to
changes in environment & other species
or
shift trigger GVHD
GVHD diarrhea trigger shift
steroids for GVHD
or
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
can provide greater confidence in distinguishing interactions from similar response to environment
Thanks
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
Johnathan Golob
Andrew Wiser
Erin de la Cruz
synchrony
spurious
correlations
environmental
forcing
species
interactions
shared noise (sampling)
problems with current method
correlation Based
Microbiome
Causality
Without all your hard work none of this would be possible:
vaginal longitudinal microbiome data comes from:

55 participants of current BV R01 (current)
(special thanks to Congzhou & Nette)

20 participants from the PloS One Cohort
30 day longitudinal (2009-2010)

14 participants from the STD Clinic Longitudinal
7-14 day longitudinal Cohort (2006-2008)
infant weigth gain data comes from:
Smith et al. Gut Microbiomes of Malawian Twin Pairs Discordant for Kwashiorkor. Science (2013) : 548-554
distinguish environmental forcing from interactions
54 Malawi children with either gut microbiomes sampled every 3 months, every 2 months or every 2 weeks

Also measured malnutrtion with a weight-for-height z score (dist from standard deviation of WHO Child Growth Standards)
What components of the microbiome are responsible for growth (prevent or recover from malnutrition)?
Cross- Convergent Mapping Example IV
Full transcript