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Thursday, February 25, 2010

AGBT 2010 - Julie Segre - NHGRI

Human Skin Microbiome

Each human cell has the same protein encoding potential. Microbes are more diverse and dynamic than human genome.

Our interactions with our environment strongly effect our microbiome - they bring a huge diversity of interactions - and may affect our ability to develop personalized medicine.

Skin: Barrier to infection, but also home to our microbes.

We can investigate through the use of 16S rRNA. 16S rRNA is more variable in loops than in stems. This has to do with conservation of structure.

HMP spent a lot of focus on amplification strategy that accurately represents bacterial population (match with cultured isolates) with Sanger and 454/Roche.

Do we get more information if we seqeunce than using the traditional culture based methods.

Test: Parallel swabs - culture on various agar/ vs seqeunce. You see a huge bias in the culture samples. Staph are very good at culture - so it swamps out the other actinobacteria, cyanobacteria, etc.

Do this for the whole human body - eg, rash diagnoses are dependent on *location*. Human cells are same, but bacteria change depending on the environments. Oily vs dry, vs moist, vs.... etc. [Lets not go too far with this.]

[Neat.] Variation between sites is greater than variation between individuals.

[also neat:] More diverse sites are more stable.

Sanger sequencing doesn't give nearly enough depth about the rare factors - which is a huge component about what's going on at any given site.

4 vignettes: [I only counted 3... maybe I missed or grouped two together.]

1. Kid with Severe Eczema. (Atopic Dematitis)
* Chronic episodic itchy red skin
* Prevalence 15% in USA
* incidence has trippled in last 30 years
* Treatment: topical or oral antibiotics and /or steroids
* 50% of children with moderate to severe AD will go on to develop asthma and/or hay fever. (Have morbidity and mortality associations.)
* Compare with healthy twin: During flare, diversity is lost, staph is overabundant. Post treatment, diversity returns.
Ask: does 16S have the granularity we need to understand AD? Will we need metagenomics? (Bacteria are underdoing gene transfer/sharing - it may not be sufficient.)

Test: use 454/Roche-XLR to find out what the genome looks like.
* Gene content is HIGHLY variable. 80% of the genes are identical - 20% of genes are variable. The genome sizes, however, stay relatively constant.
* 80% is core genes
* 20% are defense mechanisms, etc.

Why do we care about staph?
* It's the most common hospital-acquired infection.
* they form biofims
* infect on medical equipment.
* when staff wakes you up at night to do a blood draw, they're looking for staph - do you have staph in your blood?

Use genomics to identify difference between "medical device" vs. "commensal" strains.

2. Does your immune system shape microbiome.
* Patients seeking cancer treatment often become temporarily immuno-compromised.
* Patients lack Th17 Cells.
* Serratia predominates on Hyper-IgE skin, lack of other Proteobacteria.

3. Chronic skin wounds: A complication of many diseases, especially diabetes
* Half of total cost of skin diseases ($10 billion/yr)
* antibiotic treatment common with minimal efficacy
* Many bacteria associated with delayed wound healing based on culture studies.
* Diabetic mice model
** diabetic mice have increase in staff, and microbiome composition change.
** retain expression of immune response genes longer than non-diabetic
** Staph abundance positively correlates with skin expression of defense genes.

How to bridge genomics with microbiology.
* Still don't have a good equivalent of a LOD score

To do:
* greater bacterial diversity than appreciated by pure culture studies.
* Establish bacterial baseline of human skin sites
* Informatics chanllenges
* ... [2 more I missed]

Human Microbiome Project (HMP)
* not about disease, but about health.

Are pro-biotics and anti-biotics promoting health or disease? Is this neutral to our health or our environment.



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