 So what we generally try to address in any meeting of this type is sort of how did we get where we are, where are we now, and where are we going. So I am now the presenter. I have power. This is cool. I might be, but my down arrow still isn't working. But my space bar perseverates. Okay. All right. And as Eric mentioned about four years ago, we released four and a half now, released our strategic plan that was developed basically as Eric came on, the process had begun, but we really sort of put it into place in that, in February of 2011. As Eric mentioned, this was to go from, really, from the sequence to clinical applications. This was new for us. The Genome Institute of Genos started as the genome project, which was focused on the structure, the sequence, and we had since developed and looking into the function of the genome. But this was a new thing where we were really trying to apply this in health and disease. And as with any technology, we asked ourselves, or any approach, we asked ourselves, well, what do we really want out of this in medical care, and written by these guys, and really sort of five things. You want to identify risk. You like to prevent disease, improve diagnostics and treatment, and you like to increase access, make it available at a reasonable cost to everybody who might benefit from it. You've probably heard us talk about the five domains of genomics research. The structure and function of the genome, as I said, are bedrock, and they will always continue to be. We are the institute that really does that kind of work, and no one else does. Understanding the biology of disease is something that we moved into in the genome-wide association era with looking at associations with diseases and other clinical phenotypes. But really what was new in this plan was the science of medicine, really trying to get at improved diagnostics, treatment prevention, et cetera, and then improving the effectiveness of treatments so that patient outcomes were actually improved. And genomic medicine is focused on these two areas, as you see here. Eric mentioned we had a strategic meeting actually now about five years ago, almost to the day, planning the future of genomics, and at that meeting, some of you who were there will remember that the room was kind of divided into two. There was half of the room was saying, this isn't ready, it's not time, don't you? And we need to learn much more about it before we start using it in people. And the other half were saying, you guys don't understand, this is out there now, it's happening, and you need to get in front of it if you want it to be done right. And so we kind of picked a hybrid of those and decided to move on in this area. And one of the things that we tried to do was to say, all right, let's take stock and figure out what really is out there. And again, as Eric mentioned, much at the urging of Jeff Ginsberg, who was telling us, yes, this is happening out there. We did what we typically do, we invited a bunch of really smart people with almost no notice, and in this case, didn't even pay their travel, and said, you know, if you'd like to meet us at O'Hara Airport on June 29th, we'd love to have you, and we're going to talk about genomic medicine. And about 20 groups came. We agreed we would define the landscape and figure out what was common across the groups, particularly try to develop some kind of a nation roadmap for how groups who were not in this space might try to get there, and then identify common infrastructure and research needs. And that led to one of the white papers that Howard mentioned, and one of the things, among the things that we found there was that there was a lot more than we had anticipated going on. Most of these efforts were in isolation, so they didn't know about each other and they weren't building off of each other. And we also found that they had many barriers in common, such as a lack of evidence of promoting implementation, and that then was leading to a lack of acceptance. There was also, there were challenges as there still are in interpreting variants. Back five years ago, it was comparably easy compared to what we have now. There was also a lack of expertise in trained clinicians to use this information, lack of standards, and difficulty in integrating into electronic medical records and clinical workflow. So as you heard, we established a working group of our advisory council. Our advisory council meets three times a year, and we have several working groups that provide input on specific topics. And you've met the group sitting along the base of the U there, with Eric and myself and Laura Rodriguez as the sort of ex-officio NHGRI members. You'll also see all eight of them as the panel leaders. And because Eric and I were setting up the meeting, Laura is the ninth panel leader, so she'll get to do that with the ninth panel. The charge for the working group is to assist in advising our council and us on research needed to evaluate and implement genomic medicine. And you can see the charge here reviewing current progress, identifying gaps. We also try to identify key advances and make those available to the public, to news media when they ask, you know, what have you done for us lately? That sort of thing. They plan these meetings. This is the eighth, as you can see, on timely themes. So we try to identify generally at the, you know, over dinner the night between the two days of the meeting, as we'll be doing tonight, what should be done in the future and how things are going currently. We try to facilitate collaboration and coordination and explore models for infrastructure support of all of these efforts. We describe these efforts on our NHGRI website. You can see here, we publish the notable accomplishments kind of broken down by a series of themes. In collaboration with our Division of Policy Communication and Education, DPCE, we also work on some of the policy and education efforts. Eric mentioned that we had come up with a definition of genomic medicine. There wasn't one at the beginning. There was a lot of debate as to what it was. Our definition is purposefully narrow, because as you said, we're a small institute. But still, we have one there, and it really is. You know, what we're talking about is implementation, using an individual's genomic information in their clinical care. Also, our policy group has been very active in addressing challenging issues such as reimbursement, dealing with the Centers for Medicare and Medicaid Services, as well as the Food and Drug Administration in some of the challenging issues related to next-generation sequencing. They've recently published, for example, or posted a guide to investigators for applying for investigational drug exemptions, IDEs, from the FDA. And our Genomic Healthcare Branch has happily taken over the Inter-Society Coordinating Committee for Pre-Precisioner Education in Genomics, or ISCC, a very large and robust education effort that grew out of these meetings. So after the first meeting, we had a second in December of 2011 to promote collaborations, a third looking at various stakeholders, policy, and otherwise, mainly reimbursement, actually, and laboratories. Physician education in January of 2013, we brought together federal agencies in May of 2013, and global leaders in January of 2014, where we met some of our colleagues from outside borders. And you'll notice that these were happening every six months. This got to be exhausting for us, and it was killing our budget with all of the things that were going on. So we slowed down a little bit to every nine months. We had one on genomic clinical decision supports back in October, and another, obviously, this one now. All of these meetings, except for the first, are webcast and streamed. They're video archived. They're all on our website. All of the slides are available as well, as well as meeting summaries, and some of them actually then produce subsequent white papers. But we've found, and have heard, that this is something that really is a useful resource to those trying to implement genomic medicine. Just to kind of look at some of the outgrowths of our meetings, this kind of reminds me of a planarian, but at any rate, looking at this little fellow when he or she was, I don't know if they have, well, we don't go into that. Anyway, when it was small, with our first meeting, we then led directly into what we called the ClinAction meeting, trying to identify actionable variants, which was something that all of these groups had been trying to do sort of in isolation. That led directly to our clinical genome resource that you'll be hearing a lot more about today. It also led to the addition of a pharmacogenetic sequencing array in a collaboration with the National Institute on General Medical Sciences and IGMS's Pharmacogenomics Research Network, taking their array and applying it in the Emerge Network in 9,000 people, which has been a very fruitful collaboration. Our second meeting led directly to the Ignite program, our demonstration projects where we're trying to bring genomics into a wider array and more diverse settings and more diverse populations. Our third meeting led to a sub-meeting with a group of payers. We're still pursuing those interactions and they have borne some fruit. The fourth meeting on education led directly to the Inner Society Coordinating Committee, which has really taken on a life of its own and now is under the leadership of Bob Wilden. Our fifth meeting actually led to a number of collaborations. This was the Federal Stakeholders meeting. I've put these in dotted lines not to imply that we were responsible for CMS, FDA, or the Air Force. So we didn't produce those, but we did develop some very good collaborations with them that are continuing. We did, however, come up with a trans-NIH working group on clinical applications of genomics and we have several members of that, Barb Connelly, Kachel, Dina, and Wendy and others here at this meeting and we thank you for being there. I understand several more are listening to the webcast. The sixth meeting on global leaders led to a global genomic medicine collaborative. We held the sixth meeting in collaboration with the Institute of Medicine and they have then taken on the support and management of the G2MC, which is kind of an implementation arm for genomic medicine globally, trying to understand what's working in different kinds of settings and what might be transportable to other groups. And that group then is related to the Global Alliance for Genomics and Health meetings that are happening later this week that some of you are flying off to this evening and our apologies for making you extend your travel time away from home, but at any rate. So we recognize that those are close collaborations that need to be facilitated. And the G2MC actually led to a meeting on research directions in Stevens-Johnson syndrome, Toxic Epidermal Necrolysis, or SGS10, that was held just a few months ago because we wanted to take sort of an interesting model that we saw in Southeast Asia and see how it might be applied elsewhere. One of the things we found was that there's almost nothing being supported in research in this area at the NIH and yet it is a paradigm of genomically mediated adverse drug reactions that might be preventable. So all of those outgrowths, the seventh meeting on Genomic Clinical Decision Support has led to stronger collaborations with the Institute of Medicine's Genomic Roundtable, particularly in implementing CDS. And here we are today. So as Eric said, there's been a lot to come out of these meetings and many of them have been really tangible product projects that you'll be hearing about today. So that's kind of the, how do we get here? I'm a big fan of Gary Larson, so we're entering the middle of nowhere. Well, this is just going from bad to worse. Actually, we're not going from bad to worse. We're in a really exciting time for genomics and genomic medicine. This is a list of all of the programs that we consider to be sort of the focus program. We sent out descriptions of all of these because one of the things we didn't want to do was to just have a parade of people coming up describing the program and sitting down. We thought we could do all of that kind of in advance. And so, and I won't do that now because somebody took most of my time, but I won't go into that either. But at any rate, just to describe or show them to you in a list, the Undiagnosed Diseases Network I should mention is a program of the Common Fund of NIH, so it's supported by all of NIH, is building on our Undiagnosed Diseases Program, sorry, that began as a collaboration between the NHGRI's Intramural Program and the Office of Rare Diseases Research. We still have a large footprint in that and we're managing a large part of it. So, and it's obviously clearly related to the kinds of things that we're talking about today. Then there's the Insight Program, Newborn Sequencing, Clinical Sequencing Exploratory Research, looking at integrating genomic sequence in a variety of different programs. The second emerge, 2011 to 2014, actually began right on the cusp of our publishing strategic plan and having that first colloquium. And one of the things we were able to do was kind of get them to take a little bit of a right term and say, not only are we continuing the biorepository and electronic medical record research that we've been doing in Emerge I, but we're really now trying to have some small implementation projects to learn a little bit better how to do this on a more system-wide level. As I mentioned, we implemented the Emerge PGX project, Emerge III, so Emerge is in an awkward phase right now, it's right at that stage of renewal and we anticipate awards for Emerge III being made later this summer, but the plan there is really to identify rare variants in 25,000 patients, determine their penetrance and actionability based on some of the experience that we've had with the Emerge PGX. Ignite project is, as I mentioned earlier, really trying to disseminate this model beyond specialized centers into less specialized clinical settings, and then the clinical genome research to develop consensus information on variants relevant for clinical care. So Howard, I have nine, 10, is that right? Yep, yep. Okay, so maybe to give you an overview of how this looks, we're looking at two axes from the depth of patient characterization going from, perhaps not too deep, down to the bottom of the y-axis in very deep and careful characterization and breadth of implementation along the x-axis, and if you consider this then the UDN is probably an example of one that is very, very deep. Patients are typically brought in for a week of clinical characterization and that's something that we can't do on a large scale, obviously. N-Cite is similarly very deep in some of the programs in particular and the clinical sequencing exploratory research program a little bit more broader looking at system issues or hospital issues as well as dealing with individual patients. And also all of these are sort of testing multiple models where we're really trying to see what works and what can be codified. Emerge, on the other hand, tends to be a little bit more unified, particularly in its third phase, it will be much more of an approach on a system-wide basis and ignite. Again, trying to deal with these things on a system-wide basis for evidence generation as well as impact in dealing with institutions and clinicians. So, those of you with a seizure disorder, please look away. I'm just gonna flip right past all of these slides describing these programs because I'm a little bit out of time. One thing I did want to sort of pause on was the fact that having done some sequencing now from the experience that we've gained from multiple programs, we've recognized one of the biggest challenges for institutions is really what do you do when you find these abnormalities or when you find sequence variation and you may not know what to do with it? How do you report that back to patients? How do you deal with clinicians? This is something that has been studied. Actually, it began in the GWAS era when we started finding, to our surprise, people with Kline-Kelter's syndrome that was on diagnosed returner syndrome, sort of first detected in the sex chromosomes because those we could be really, really sure of. And the other things we were seeing, we thought, well, maybe those are just artifact before those sex chromosome differences there where they were sort of incontrovertible. Some of you were involved in those early discussions of what do we report back, et cetera. In Emerge, it's a bit of a challenge, more so than in many of the kind of classic genome-wide association studies because many of these centers had an interaction with the patients. They were dealing with them directly and so trying to figure out how best to do this. And we're recognizing now that as sequencing generates all of these findings, institutions are going to have to learn what to do with it and we're gonna have to learn what the implications are. Again, kind of flipping through my apologies to all these programs that are lovely. We'll put these slides on the website so that you can see them and put up the genome resource again. Okay, sorry. Okay, and we'll get to putting the pieces together. So this is one of my favorite cartoons from the genome project. I think I found a corner piece here with the three billion pieces. And so kind of looking overall, you have two matrices in your materials. We sent out a revised objectives matrix just this morning. That was because I forgot to include the Air Force program and so sorry Ruth, but we have it incorporated now. But what I tried to do was to look at the focus program, sort of the six main ones that we have in NHGRI and kind of boil down some of the major topics there. So this gives you a feel for the programs that are working in genomic diagnosis. Recognizing that these are probably working in that area as well, but it's not really an emphasis. LC issues related to sequencing with several programs addressing that, integrating sequencing in the clinic, clinician, patient, education, et cetera. And this is kind of how we think about these, all of these are just about all and probably there should be a positive plus sign here are trying to deal with defining and sharing implementation processes. I should note that we have the slides networked and you all received a WebEx link or a GoToMeeting link in your email. Because this is a big room and we have lots of slides in that, I would encourage you if you're as myopic as I am to go ahead and log into the WebEx so that you can see the slides on your screen. I think that will make it much easier as we walk through the day. So, we've heard a little bit about how we got here. We've heard where we are now and really the golden question is where are we going? And that's what we're relying on you to tell us in the next day and a half. And this is going to perseverate again. So, you'll see from the agenda, we set it up as nine panels. We do have a panel table here but I think in talking with the GMWG members, our feeling was that this kind of puts them off and you know, switch around or something. And we'd rather have more of a discussion around the table. So, we'll probably do most of the discussion from our seats here at any rate. These were the nine topics we settled on. There are others that could have been addressed. You'll notice that health economics is not on here, there are a number of others that are not on here. But these are the nine that we went with. Excuse me, we asked each of the panel leaders who are the GMWG members and their panels to address the importance and impact of the topic, what current programs are addressing it, what gap areas they are, what potential synergies and what training opportunities they might be. So, you'll be hearing that through the day. We've asked for each of the groups to limit their presentations to 20 minutes. And I have these really obnoxious signs that I hold up that say you've got five minutes or two minutes or one minute left. So, we will try to hold you to that. And then we'd like to leave half an hour for discussion and really a robust discussion. Again, a little bit difficult in a big room like this, but we're asking the panel leaders to moderate that. And you can moderate it from here, you can wander around, you can do it from your seats, whatever feels best to you. Then at the end of that, the last five or 10 minutes we'll ask the panel moderators or whomever they have delegated to do this to show a summary of the key points. And of course, we'll be putting these together and at the end of the meeting, Howard and I have some summation efforts. And we may, depending on our discussion tonight, we may try to write this up as a white paper for publication. So, many thanks. I'd like to express particularly to Rita Chambers and Teji back in the region to Bruce, to at least two back here. Thank you so much. They've been responding to my emails all weekend and I really appreciate that. And also Jackie Ogis and Ellie who are going to be our note-takers for the summary of the meeting and really wonderful efforts by everyone there. The, particularly our program investigators and participants who are doing all of the work that you saw sort of fly by there that I didn't get a chance to talk about. And the many NHGRI staff that are involved in this effort, especially the also the GMWG. Pearl O'Rourke I should mention is an emeritus member of GMWG, she actually managed to escape. But don't any of you get the idea that that's going to be possible for you as a hotel California. So, and then, and particularly also our genomic medicine meeting participants on the web as well as in the room. So, I think with that I will stop and I'm happy to answer any questions. Thank you. Questions for Terry? We'll transition over to Jeff who's almost up there. So, Jeff, are you ready? You are ready.