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Saturday, February 7, 2009

Andy Fire, Stanford University - “Understanding and Clinical Monitoring of Immune-Related Illnesses Using Massively-Parallel IgH and TcR Sequencing”

The story starts off with a lab that works on small RNAs, which believe they form a small layer of immunity. [did I get that right?] They work in response to foreign DNA.

Joke Slide: by 2018, we'll have an iSequencer.

Question: can you sequence the immunome. [new word for me.] Showing a picture of lymphoma cells, which to me looks like a test to see if you're colour blind. There are patches of slightly different shades...

Brief intro to immulogy. “I got an F in immunology as a grad student.” [There's hope for me, then!]
Overview of VDJ Recombination, control by B-Cell differentiation. This is really critical – responsible for our health. One Model: If something recognizes both a virus and self, then you can end up with autoimmune response.

There is a continuum based on this. It's not necessarily an either /or relationship.

There is a PCR/454 test for VDJ distribution. Under some cases, you get a single dominating size class, and that is usually a sign of disease, such as lymphoma. You can also use 454 for this, since you need longer reads, and read the V, D and J units in the amplified fragment. Similar to email, you can get “spam”, and you can use similar technologies to drop out the “spam” from the run.

To show the results of the tests for B-cell recombination species, you put V on one axis, J on the other. D is dropped to make it more viewable. In lymphoma, a single species dominates the chart.

An interesting experiment – dilute with regular blood to see detection limit – it's about 1:100. For some lymphomas, you can't use these primers, and they don't show up. There are other primers for the other diseases.

So what happens in normal distributions? Did the same thing with VDJ, (D included so there are way more spots). Neat image.. Do this experiments with two aliquots of blood from the same person. Look for concordance. You find lots of spots fail to correspond well at the different time points, but many do.

On another project, Bone Marrow transplant. Recipient has a funny pattern, mostly caused by “spam” because the recipient really has very little immune system left. The patient eventually gets the donor VDJ types, which is a completely donor response. You can also do something like this for autoimmune disorders.

Malfunctioning Lymphoid cells cause many human diseases and medical side-effects. (several examples given.)



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