Thursday, 6 September 2012

Immunogenomics is coming

The immune system is becoming easier to investigate as new methods based on nextgen sequencing are published. I am not an immunologist and the complexities of the immune system for me are stuck back in the days of my undergraduate training. And that was in the 90’s!

Nature and the HudsonAlpha Institute are hosting the first Immunogenomics conference next month bringing together scientists from many disciplines to learn about large-scale immune sequencing projects; epigenetics and the immune system and many other topics. Immunogenomics looks like it is going to make headlines next year.  

There have been several papers describing HLA typing (e.g. Gabreil 2009 & Bentley 2009 using 454 and more recently Wang 2011 using HiSeq) and many groups are working on using next-gen methods to replace older tests.
 
A new product from Sequenta is aiming to make this kind of analysis simple to do for any user. The Lymphosight platform uses a multiplex PCR to amplify the IgH, IgK, TRB, TRG, TRD immune cell receptor loci, allowing each T or B cell to be characterised and counted. Immune cell proliferation in response to disease and other studies might be far easier to carry out using this new kit. With 100’s of millions of reads coming from HiSeq, and eventually Proton, even fairly rare immune cells should be detectable in a high background. 


Lymphosight workflow from Sequenta website

The company discuss a test they ran where sequences associated with a B cell tumour were diluted into a normal background at 1:1,000,000. They got very reproducible, quantitative results and a useful dynamic range that compares well to flow cytometry methods currently being used. They expect Lymphosight to be useful in monitoring of minimal residual disease.

David Haussler Director, Centre for Biomolecular Science and Engineering at UCSC said 'We can read genomes from your immune cells. They adapt throughout your lifetime so they can protect you from diseases. Reading those genomes will be important, and you’re going to hear a lot about them next year.'

I recently visited TRON, a spin out from Mainz University Medical Center, where they are conducting translational research in the field of oncology and immunology. One of their aims is to take personalised immunogenomic markers and turn these into personalised Cancer vaccines. The head of TRON, Ugur Sahin just published a very interesting article in OncoImmunology where they describe using NGS to demonstrate a proof-of-concept for identification of immunogenic tumour mutations that are targetable by individualised vaccines. They analysed a melanoma cell line and found over 500 non-synonymous expressed somatic mutations, one third of which were immunogenic. From these they made long peptides of 27aa length and tested these for immune response. 11 of these immunogenic tumour-specific peptides effectively immunised mice against the Tumorigenic cell line (see figure 1 from their paper below).



I am sure Sequenta are hoping groups like these will be using Lymphosight to do perform their analysis of the Immune repertoire.

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