A Landmark N of 1 "Panor-omic" Study Eric Topol, MD, Genomic Medicine, 08:39PM Mar 17, 2012

[F, Calla & Luca]

Here is an interesting transcript about human genotyping and  gene expression:

A paper published in Cell is a tour de force of 'omics in one indivudal -- the senior investigator, Dr. Michael Snyder. Here we discuss the findings and implications of such a compehensive 'omic assessment.

Chen R, et al. Personal omics profiling reveals dynamic molecular and medical phenotypes. Cell. 2012;148:1293-1207.

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Below is a transcript of Dr. Topol's post "A Landmark N of 1 'Panor-omic' Study." We look forward to your feedback.

Eric Topol here to discuss a landmark paper in the journal Cell. This is the first time we've actually reviewed a paper in Cell on the Genomic Medicine site. It's a particularly unique paper. It is an N of 1, "panor-omic," comprehensive, very detailed 'omic study of a single individual. In this case, the individual is Michael Snyder, a geneticist from Stanford University, with 39 other collaboratives, predominantly from Stanford, but also from Yale and Spain.

Basically, what this entailed was a serial examination of 20 different blood draws that Michael Snyder had over a 14-month period. During that time, virtually everything you could imagine was assessed. Not only was there DNA sequencing at very high, deep coverage, high accuracy and resolution, but also there was gene expression. There was RNA seq to detect any issues in RNA. There were protein and metabolite assays that were comprehensive, along with autoantibody, along with micro RNAs -- all of this over a 14-month period.

As you would expect, the susceptibility to some diseases through, not just common variations, but rare variations were detected, including a key rare variant associated with diabetes mellitus and another rare variant with high penetrance for aplastic anemia.

But what was interesting during this study that spanned over 14 months was that Michael Snyder had two viral infections. Right around 300 days, he had a viral infection that led to a marked increase in genes that were associated with inflammation, interferon, and the conventional serum CRP that we measure. With that, his glucoses shot up, as well as his HbA1C, even up to about 6.7% from what had been normal, with fasting glucoses that were in the mid-100s. Then he went on to a lifestyle program to lose weight and exercise more, and was able to reverse the clinical manifestations of diabetes.

This is a remarkable paper. It is an N of 1 study with an exceptional amount of billions and billions of data points across all the different 'omics, and even expanding into autoantibody formation. It also tells us about how gene pathways and gene expression change over time. It's not just a measurement once, it's dynamic -- the variants in one's genome, as they can be expressed differently in different tissues, they also can be expressed differently as a function of time. It's highly instructive.

The question, of course, is, can this be done, this type of study, with an amazing amount of bioinformatics and data -- can this be done in the real world. Should it be done in the real world? Well, certainly, as we have discussed in prior segments, this is something that could be of immense value in patients with rare, idiopathic, we-don't-know-the-cause, conditions. Certainly for serious cancers, some type of "panor-omic" view could be helpful if we could do this quickly before therapies were started, or, of course, in refractory or relapsed cases.

Ultimately, when this is all done through a means of algorithm software to process all this data and when it can be markedly reduced in expense, some of these components will be useful for prevention as was used in this classic case.

For example, with Michael Snyder being at significant risk, of developing aplastic anemia, he can go into prevention mode and surveillance, just as he did with the known risk of diabetes. In fact, much of this I had written about in the book Creative Destruction of Medicine -- but now it's already been actualized as of March 15, 2012. When you combine all these 'omics with wireless sensor data and anatomical data through high resolution imaging, like the ultrasound pocket echo, you get an N of 1 that is truly unprecedented.

I'll be interested in your views about this "panor-omic" N of 1 landmark study, a tour de force. It will be interesting to see what you have to say. Thanks very much for your attention.

 

[Nancy, Ned, Clancy, and Charlie]

This is extremely interesting information.  

"...can this be done, this type of study, with an amazing amount of bioinformatics and data -- can this be done in the real world. Should it be done in the real world?" 

And, does susceptibility mean one  will develop that disease?  Can being proactive, prevent?  Does knowing probability of a disease mean that 'real world' people will act to prevent if possible?

[F, Calla & Luca]

Well, for sure having this done in the real world now would be impossibly expensive if you could find someplace to do it, I think. As to whether prevention would work, a good preventative measure(s) would have to be available. I see no point in knowing about diseases you might get if you can't allay them.

[Maryann,Roo and Tigger]

I am fascinated by genotyping and genetic expression.  Once we did not know about DNA, then we thought DNA determined everything.  Now we know that nature and nuture can affect gene expression.  What next?

[F, Calla & Luca]

Good question. Sometimes the more we know, the less we know.