 Well, thanks very much. I'm sorry I wasn't here yesterday. There was another meeting just down the road on wireless medicine. And I want to say I'm really disappointing you. I know we're not having any slides, so I know that's really a letdown. But I just was going to review and discuss a few of the programs we have going on at Scripps. You may know that at Scripps, our CTSA is based on genomic medicine. This really brings together the basic science people at the research institute with the clinical folks at the health system, which is the largest health system in San Diego. So we have one program that is really modeled after the Medical College of Wisconsin. We call it ADM for idiopathic disease of man, particularly concentrating on adults. So really the counterpart of what MCW pioneered. And we have now a few individuals in the queue. It's actually been funded by various philanthropic sources. We have enough to support 20 individuals to go through that process. And that involves sequencing of the individual with a life-threatening serious condition, along with parents or any other sequencing data that would be scaffolding the diagnosis of a causative mutation in the affected individual who is selected. And we have a big committee review, and a lot of our program was developed in concert with the folks with Howard and his team at MCW. So that's one. I'll just maybe just go through a few and then answer your questions you have. We have a big program called the Welderly, which now has over 1,200 individuals who are over age 80. Average age is 87, ranging up to 106. These individuals now accrued over four years, and we actually started it when Kelly was with us in the beginning in 2007. And this is a project that is trying to understand genomics of healthy aging, but has a really nice collaborative opportunity because complete genomics has basically set up to do 1,000 whole genome sequences of the 1,200 people we've accrued, and that data will be all finished ready in March. So that was about $5 million worth of free sequencing for us. We've done exome sequencing on about 350 of those individuals, and we have some interesting findings, but obviously we're looking to much more data from the whole genome sequencing of this large cohort. But the other flip side of genomics of healthy aging, these people have not had any chronic illnesses, there are no medications, they're cognitively intact. But the other thing is, of course, using it as a resource is predominantly European ancestry over 90-some percent for a control group for sequencing of other late onset conditions. So that might be an interesting opportunity for collaboration. A third area that we are pretty heavily engaged in is in day-to-day practice of genomic medicine is in pharmacogenomics. And we started back in 09, a systematic program of cytochrome genotyping for clopidogrel plavix, which after the extinction of lipid tour as a proprietary drug is now the number one prescription drug in the world. It won't be for very long because in the months ahead it too will become a generic. But for the moment, that's especially important because, as I think you know, it's a drug that has a lot of variable response, and Alan and the group at Maryland has really led to charge in that work. But we have been systematically genotyping all those individuals to get a new prescription for a clopidogrel. We're getting a stent, we also do as needed platelet response to look at the various alternative therapies, and then I think along with Dan and the group at Vanderbilt they have a similar program, and I'm not sure if there are other programs like that. But we've also done now exome sequencing and have three other significant findings at least to add to that, and we have a point of care genotyping set up first now with a device that we're able to get the CYP-2C19 multiple alleles that are of interest in about 20 minutes. So before the patient ever gets into a cardiac cath lab, but we also have just started a pilot with a company from the U.K. called DNA Electronics, which is a handheld genotyping system. We'd be happy to collaborate with anyone interested, but that can actually get accurate genotyping in about 10 to 12 minutes on up to eight different SNPs. So we're going to take that into other areas. We already have started a program with Interferon, and that is just genotyping IL-28B for people with Hep-C. So all individuals who have a new diagnosis of Hep-C, which is a very common, very large program at Scripps, get front-ended genotype to see whether they respond to Pagylated and Interferon or go on to other experimental therapies. And then we're hopefully going to start in the new year a systematic program on Metformin. We've done excellent sequencing to understand the variable response of Metformin. I think you're familiar with at least 20, 25% of people have little to no response to Metformin, which is of interest since there's about 370 million diabetics on the planet, and a large proportion of them are taking Metformin for no good reason. And then the last thing I just would mention is obviously like everyone here, we're interested in cancer sequencing. We have a program we call HUTS, which is human tumor sequencing, and we have multiple individuals in that program. It's very much modeled after like the one that was just published last week in Science Translational Medicine in the Michigan program. I don't know if that was reviewed yesterday. Is anyone here from University of Michigan? It's a really excellent program. I think if you haven't seen the Science TM paper, and then there's an accompanying editorial in Science last week, which is really nice to describe it, but basically, yeah. So the program is just as you might expect, paired sequencing of tumor specimen and germ line DNA, exome sequencing of the tumor specimen, and also RNA-seq. So those are basically the tools that are used. They presented in the Science TM paper for individuals, and also the response that they had to the drugs that were selected, at least in a couple of them, on the basis of that. So we basically have a very similar program. We've had several individuals run through. Our biggest problem and challenge at Scripps was to get the pathologists to have tissue frozen for us rather than having an FFPE. We've also, of course, had to work with individuals who couldn't get another biopsy and had to deal with that situation, but that's not really the primary focus of this project. So at any rate, we have several individuals now who've had sequencing, and it seems like that's a great opportunity for collaboration, because if all those individuals could be pooled, everyone that's being done on a clinical basis in the country, that obviously would help everyone, not just the patients involved, but obviously all the investigators. So that's pretty much what we're doing, at least of relevance to some of the collaborative opportunities in genomic medicine. We also have a course every year, March 1st and 2nd, this coming year. Many of you have participated. It's the future of genomic medicine. It's our fifth annual course, and it's a nice time to vet all the ideas of how, like what you're doing in this forum, to try to take genomics into the real care of patients. So questions? That's about it. Questions for Eric? Eric, could you give me a comment? I need idea about pulling together all of the patients being done clinically. Is there like one or two vendors that one could basically go to and say, tell us everybody who's doing this clinically, so that we'd have some way of kind of capturing them and inviting them and that sort of thing? So you mean in terms of the sequencing side? Yeah, I think unfortunately there's a lot of nodes of entry. The some are sending the specimens to complete genomics, to BGI, and others are sequencing them on their high-seconds solid. So I think unfortunately there's a lot of different ways to get there. And then, you know, I think the problem is, of course, we haven't come up with a way to easily pull all that data and deal with it, but I think it's worthwhile considering and it wouldn't be that difficult, I wouldn't think, to be able to figure that out. Yeah, if there's just, if there's some, it's just a point of entry or at least some way of getting the word out. There's probably a way of doing it. I would think Illumina would have, you know, would know at least who's bought their machines and they're willing to share that. Yeah, and actually I should have mentioned that some are also using the Illumina Clinical Sequencing Service as well. And in fact, for both, actually for all three of those, male order sequencing, more than half are cancer samples these days. So it provides a great opportunity that could be culled together. And I think the other thing, of course, is, you know, the processing the data and adding in the response to the drug selected on the basis of that analysis. I think that even just a year of follow-up would provide tremendous insight. If we had, you know, the crowd sourcing, crowd sharing of all that data, it would be terrific. So I think one question that arises from the sharing of clinical samples, of course, is what the range of utility they may have only for other clinical projects or, and maybe this is a topic for discussion this afternoon, but how does that feed into opportunities for research? They're probably not appropriately consented for that. No, but I mean, I think, for example, the project mentioned of healthy aging, as far as setting that up for controls, that's eminently poolable for sharing that data. I think it might be a useful resource. Could it, potentially, could it have the sequencing task and, you know, for any late onset disease of interest in which there's a sequencing project ongoing? So most of the clinical samples are post-mortem that he's referring to, because they're done on treatment and there's an outcome, and the outcome is often time to progression. So I don't know how that factors in, but they usually, while they were collected in a clinical setting, the DNA represents post-mortem. I have a question. I mean, the point of care genotyping is obviously a tremendous issue, and if one could, you know, collect experience with various platforms that are being pushed now by various vendors, and, you know, I think the key is going to be, you know, the accuracy and the validity of the assays, where, you know, a lot of point of care platforms have, you know, deficiencies in that area compared to the standard platforms. I think that would be a tremendous opportunity to go forward and, you know, put together a group that is actually engaged in this, and perhaps deploy some of these. If it's a handheld platform, I could just see some of us run around our medical centers and using it and then share the data that would be something. Can you expand a little bit on that? Yeah, actually, I have it. I could show it to you. I was just showing it yesterday. It's really a very impressive device. We're in the midst of validation, and some of that work's also been done at Imperial College in the UK. But it looks like it works quite well, very fast, and, you know, it's just like a cell phone device, and basically it works with a saliva or a buccal swab and remarkable. So I think the point of care genotyping is really taking off, and for certain indications, whether it be, you know, one of the, I think the ideal ones is the Plavik story. But the interferon in hep C is, I think, emerging as quite an important one, and perhaps others. So I think that would be a great, if those, if there's an interested subset of centers that want to work together on this, it would, it would accelerate now the validation, but finding its optimal clinical utility. That'd be great. What's the, I was going to ask, why can't we consent these patients? The, we're seeing more and more examples where clinical patients are consented for research, you know, through a de-identified process. I, I don't, I didn't make that statement, but I, I agree with you, actually. Yeah. I think for the point of care, a really interesting case, I think would be in, in the Warfarin situation, because one of the things that we found in our work at Intermountain has been that, you know, in doing our trials, we've been doing them in our tertiary center, where we have an anticoagulation team, and so we're really comparing how much does pharmacogenomics add to a really well-run high-performance anticoagulation team, but in a system like ours, in a system like many's around, many around the table, there's a lot of rural sites that don't have anticoagulation teams as individual docs trying to do it. My hypothesis is, is that, you know, a handheld point of care information about this might have, in fact, much bigger impact on their patient population than ones that are being managed through a tertiary medical center. And that would be, I think, a very interesting collaborative project that could potentially be done if there were enough of the devices to, to move. The question I had, you mentioned coming up with controls for the healthy aged population, which has struck me as being a very interesting idea about how you would define controls for a healthy aged population would be a dead aged population. Yes. So how are you setting up your controls? Yeah, well, we debated about this for quite some time, what would be the best controls, using those as the cases, and we came up with this elderly group that you're, I think, touching on, which people who had died earlier in life at their average age is around 70, of the usual, you know, diseases that follow suit with the population. So that's what we've used to understand genomics of healthy aging, but of course, you know, using these as the controls for, I think, ideally, health span, rather than lifespan, which is influenced by all sorts of medical interventions, is a good control group for late onset genomic projects. Getting back to your point about warfarin, I think it's a really important one, because a lot of the genotyping for drug interactions isn't done because of the turnaround time. Warfarin is a prime example. It takes days to get the results back. By then, you're already at a steady state INR, and the same is the case for clopidogrel and others. So if you had that data up front quickly, it would really influence, and inexpensively, because this is a very inexpensive test to do, I think it could really be a game changer for implementing pharmacogenomics in clinical practice. So I do think the point here, although this is just a kind of way station until everybody has their pharmacogenomic profile on their smartphone. But in the meantime, this is a good way to get that into clinical care. I'm interested. We no longer can spin a hematocrit or do a urinalysis, so I'm wondering how you got the point of care genotyping approved. Does clinical chemistry give a stamp of approval to a small number of people, or how does it work? Well, first we have to show our IRB the data of the conventional assay versus the handheld. And then once we do that for a couple hundred individuals, then we have a green light to use the point of care for guidance. So we still continue to do paired sampling just to continue, because a couple hundred people is not enough for full validation. But that's the type of program that we've been able to convince our IRB that it's okay to move ahead. So do you limit it to a certain number? Obviously the people that do the test must be the investigators on the protocol. Right. Yes. Absolutely. And does it go in the medical record? Yes. Oh, sure. But I think, although there still is a lot of point of care testing done, like for example, platelet response in this setting is a point of care test as well. So not everything is a central lab. And that's often used as a corroborating tool for designing the best drug, alternative drug in this case, or drug dose. I mean, recently there's been studies that show tripling the dose of copitagrel is the only way to override even the carrier state of the loss of functional leals. I was just curious about the thousand genomes that Complete Genomics is doing. Do you have plans to make those available somehow? Yes, we do. In fact, that's why I mentioned it as a point for potential collaboration. When we did that collaboration agreement with Complete, it was with the intent to make that data available as best as we could with the genomics research community. So that is the goal. Next is David Craig from TGen.