 Let me start with a series of thank yous, which certainly are appropriate. First of all, I want to thank all of you for coming. It's always so gratifying to put out, to make a list of people we want to come to an important workshop for our institute, put out these invites, and then just seeing the incredibly high fraction of people that are willing to travel here to help us. And so once again, the community of individuals that we have the pleasure of working with are always incredibly loyal, incredibly helpful to us, and that's always a very gratifying part of the job. I want to pay particular thanks to the workshop organizers. We put a small group of people together to help us sort of think through the agenda and to organize some of the details of the workshop. So Eric Boerwinkle, Carol Volk, Aviva Gabb, and also John List, who unfortunately can't actually be at the workshop. But for the four of you, thank you for your extra effort. I also want to just thank in general our advisory council. We have a couple of representatives, at least two or three, from the advisory council here. They have been actively in discussions with us about the ENCODE program. They always are, and are already strategically thinking about the kinds of things that we're going to be discussing at this workshop. And I can certainly assure you that the output of this workshop and the discussion of this workshop is going to be a major focus of discussion at upcoming, and I mean plural, upcoming council meetings because clearly this assignment is very important for the institute. I also want to thank the advisors that have always been associated with the ENCODE program, at least the last few years in particular. Those advisors, and again, it's gratifying to have people who are willing to help give us input about important components of our portfolio, and certainly ENCODE is among those. And lastly, I want to thank the people who either are tuning in live and we are video casting this live, or people who will watch this after the fact, and we will be archiving this. We're always amazed at the reason we invest in having these things video broadcast. And video archived is this amazing how many, how many more people watch these things either remotely or after the fact than we either can accommodate in this room or can afford to travel in and so forth. So it really is that deliberations that we're going to have here very much are on behalf of the community of scientists that all of us represent and it's great to see them participating at least remotely and being able to sort of see the discussions and follow the debate. And I added one more thank you last night because yesterday it was really interesting today who I knew I was going to be spending time with, and then having two things that sort of made me smile, so I thought I would share them with you. I couldn't make this stuff up. This really is what happens to me some days. It both relate to my kids. I want to actually thank you collectively and individually for helping to educate my children. And you may say, what is he talking about? So yesterday at about 1.30 in the afternoon I started getting texts from my 18-year-old son who's a freshman at University of Maryland who proceeds to say, and he started out OMG, which I've come to learn means, oh my god. I know for a long time I didn't know that. But oh my, they're talking about encode in my class and he proceeds to tell me that for about 45 minutes in his class they talked only about encode. And he finally said, wow, that's really cool. Of course, I've been telling him it's cool for years, but for whatever reason when he actually sees this, so he just thought this was way cool and had all sorts of questions. So thank you all encode consortia members for helping to educate my 18-year-old son. And so I thought it was going to end there and I probably would have never told you the story except what happened at dinner last night. So at dinner last night I'm having dinner and my daughter, 15-year-old daughter who's a ninth grader who's taking just ninth grade biology, telling me about her day, she said, by the way, don't you know somebody named Richard Myers or something like that? And I said, yeah, why? She goes, well, the whole class we saw a video of him and all he talked about was Huntington's disease and the Human Genome Project. And he's from Stanford, right? I said, well, he used to be at Stanford. She said, oh yeah, she goes, yes. Well, that's really cool. I said, you know, I'm going to see him tomorrow. And she said, no way. I said, yeah, really, I'm going to see him tomorrow. So it was like, I would have been fine with him. It just ended there. But then she proceeded to say, he's so much clearer explaining these things than you are. So I thought it was a little insulting, but I went with it. I will tell you, I don't know if any of you have struggled similarly, but I find it particularly ninth grade biology helping your children is very difficult because especially on the true false questions, they come up and you know the answer is false because of what you just read it in a code paper. You'll learn the last couple. It turns out the answer is true because you're dealing with things five years ago. So in any case, I have struggled and have actually made mistakes helping her a couple of times. So for now on, I've told her all your questions. You should just email to Rick Myers and he will explain it more clearly than I will. So that's my collective and individual thank yous for educating my children at least as of yesterday. So with that as a brief backdrop, and then I'm going to come back and talk about context. We thought it would be useful to go around the room and just do some quick intros in particular because we have a lot of very familiar faces here of people who have been involved in encode for a long time. We also deliberately invited a bunch of people who aren't necessarily part of encode, but are going to sort of help us think through the issues we're going to discuss the next couple of days. So it's important to match faces to names. So why don't we start here with David. Donna Payer on the Encode Advisory Board. I've been Reggae from Broad MIT and on the planning committee? Organizing committee. Yeah, the organizing committee. By the way, thank you. And by the way, that's a great reminder. I should have said earlier, since we're videotaping, it's going to be really important for people to not only use the microphones, and when you push the button, it'll go red, but also to get fairly close to them in that way people remote and in the room will hear. Go ahead. John. John Arshay, scientific director of NIAMS. Dan Gilchrist, program director at NHGRI. Mike Pason, I'm a program director at NHGRI. Lise Feingold, program director at NHGRI. Carol Bolt, the Jackson Laboratory and Organizing Committee. Hengstenberg, coordinator of the European Blueprint Project and of IHAC. Frank Pugh, Penn State University, outsider. Dermburg Caltech, the advisory panel. Karen Adelman, NIEHS, outsider. John Stemtianopoulos, University of Washington. I'm a member of the ENCODE Consortium. Matthew Lupien from University of Toronto, Princess Margaret, Cancer Center, and outsider, and a scavenger of ENCODE data. There you go. Hi, I'm Eric Boerwinkel, member of the Organizing Committee and also at the University of Texas and Baylor College of Medicine. I'm Bill Lowe from Northwestern University and a user of ENCODE data. I'm Arvind Chakravary from Johns Hopkins, also a user of ENCODE data, primarily of human genetics. Joe Eckert, Salk Institute, NHGRI Council. I'm Will Greenlee from Stanford, and I'm an outsider, but a user. Ross Hardison, Penn State University, and I'm a member of the ENCODE Consortium. Anjuna Rao, I'm at La Jolla Institute at UCSD, an outsider and a user. Jay Chandra, University of Washington, I'm on council and slightly involved with the technology development program. Hi, I'm Yun Bernie from the European Bioinformatics Institute. I was an insider. I'm now an outsider. You'll never be an outsider. Nancy, just since you're sitting down. Yep, Nancy Cox, Vanderbilt University, common diseases. It's great, thanks. Daniel MacArthur, Broad Institute, Massachusetts General Hospital, outsider and user. All right, the famous Rick Myers. Rick Myers Hudson Alpha Institute, tutor to Eric's children and part of the ENCODE Consortium. So I'm Mark Gerstein from Yale, and I'm part of the ENCODE Consortium. I'm KT Varley. I'm at the Huntsman Cancer Institute, University of Utah. Previous insider as a postdoc and now an outsider, hoping to be in. I'm George Carlson. George Carlson, outsider, mouse geneticist and director of the Gloufland Research Institute in Great Falls, Montana. Laurie Boyer, biology department, MIT, outsider, user, and addicted. Mike Snyder, Stanford University, members of consortia. Jeff Schloss, NHGRI. Peter Good, N-H-E-R-I. Adam Felsenfeld, NHGRI. James Coulomb, I'm a program director at N-I-C-H-D. I'm the Eunice Kennedy Shriver National Institute of Child Health and Human Development. I'm Hao Yu Wang from the Jackson Lab and Chinese Academy of Sciences and a addicted user of ENCODE data. Hi, I'm Hannah Naughton. I'm a program analyst for ENCODE NHGRI. Hi, I'm Julie Corson, also an analyst for ENCODE NHGRI. All right, we may just have to scream. But Mark, oh, hardly. Rudy, great. I think we got everybody. How do I know we were going to have all these heavy users and people who were addicted? We would have invited representatives of the National Institute of Drug Abuse to the meeting as well. But there's one coming. Oh, because we, OK. Excellent. I was half kidding, but it probably is a good idea. OK, so context. Let me explain, and then I'm going to turn this over to Elise, really what the purpose of this meeting is and it very much is a contextual one. Obviously, this workshop is intended to focus about ENCODE and beyond. I'm not going to get into the details of ENCODE. Elise is going to take the baton from me and run with some of those details. And then others throughout this workshop are going to even dig deeper and describe in greater detail some of the important aspects of ENCODE. But I just want to just frame a couple things about ENCODE. First thing to, of course, remember is that ENCODE was really built on the foundation created by the Human Genome Project. In fact, I think it's wonderful Mark Geyer is here with us because I was just reminiscing with Mark. Mark and I were actually charged to co-chair a workshop that took place. I didn't look it up, and neither of us could remember. It's either 2001 or 2002. Shortly before the Human Genome Project ended, Mark and I had different jobs then. We were both division directors within the Institute. But Francis Collins, then Institute Director, charged us to put a workshop together that would look at trying to catalog all the functional parts of the human genome. Out of that workshop came the idea of, well, it's too big of a genome to actually study right now. So let's just focus on 1%. And that gave rise to this idea of putting together partsless, both coding and non-coding functional components, first focus on that 1%, which is what was really featured in the first phase of ENCODE. And you sort of think back on that workshop, which I can vividly remember was the Pooks Hill Marriott. And I don't think any of us could have predicted that 14 years later, we'd be where we are now. ENCODE 1 came and went. ENCODE 2 came and went. And now we're sort of at the tail end of ENCODE 3, if you will. So that's sort of the history of this. But when you think about what NHGRI's portfolio looks like in our strategic vision, which I'm not using slide, so I won't show you the famous density plot or heat map, whatever you want to call it. It clearly fits very strongly and squarely in the second of these five progressive research domains that is labeled biology of genomes. It really is all about understanding how it is that the genome encodes information, focusing very much on the functional elements and cataloging functional elements, but also just thinking broadly about what infrastructures needed to really understand more broadly genome biology. When you sort of look at how we predict where this is going, it's going to be clearly a vital part of what the Institute is going to want to be focusing on. Even while we extend our reach into clinical applications, clearly we all recognize we will be needing to interpret, reinterpret, understand, characterize the human genome and other genomes for, I think, decades, but certainly well past 2020, which is about as far as any of us are thinking at the moment. So the issue I don't think necessarily is it important for the Institute or whether this is critical for genomics. I think those answers are obvious. I think most of what we want to focus on is organizing our thinking about how to put forth that effort programmatically. And we have had a way of doing this for in code 1 and in code 2 and in code 3, each of the phases. But lots of things have changed. And we should be taking stock of that, as we do with any of our bigger programs. And saying, OK, let's think about the beyond part of the title on this workshop. Now, in code has played to the Institute's strengths up until now. If you think about how we've organized this and executed it, we're consortium-oriented. We do that very well. It's technology-focused and technology-driven. We do that very well. It's resource-generating. We get addicts who love us, and we hurt some of them in the audience. And that's what we do very well. It's tended to be very relatively or mostly disease agnostic, not focusing on any one biological system, any one disease process, any one organ system. We try to take an agnostic approach, and that's what we typically do. And it's tended to be hypothesis-generating, all very much characteristics of the kinds of science that we tend to do well in our extramural part of the Institute in particular. But that doesn't mean that the work of encode is not relevant for characterizing the genomic basis of disease. It doesn't mean it's not relevant for genomic medicine. Now, the new phrase doesn't mean it's not relevant to precision medicine. In fact, it is relevant for all of those things. And I suspect that the part of the reason why we know we have a large user base, and many people addicted to encode data, is precisely because they're using that for studying particular physiological processes, particular diseases, particular medical applications of genomics, and eventually paving the way for an era of precision medicine. So all of that sort of makes sense to us. And in fact, it makes so much sense to us that we recognize that many things have changed, because we've gotten better knowledge through encode and other efforts about how the human genome and other genomes work. And it also means, though, that with better knowledge and new technologies, that there are other things that can be addressed that maybe encode hasn't been addressing directly. And that's why, for example, we have deployed related programs and other efforts, like the NIH Common Fund have deployed programs that very much are complementary with what encode is doing. And that part of the taking stock at this meeting is also to look at that, because there are a number of new programs, or programs that have matured in the last few years since the last phase of encode was kicked off. And if you notice in particular on the agenda, we will start to go through those about a 3 o'clock today. And the idea was to sort of just take a tour through some of the programs, like genomics and gene regulation, like sort of functional variation, understanding the functional significance of non-coding variants, which is labeled here as FunVar, but you'll hear that's really not the official name. And there's others, such as GTechs and links and others. Some of these are our programs. Some of these are Common Fund. And one of the things we really want to have you help us think about is how these different programs touch each other, interact, synergize. And with that in mind, what's missing and what might the next phase of the beyond, whether it's encode or something beyond encode, what that might look like. So we do this, as I said, for other programs. Some of you participated in the major workshop we had back in late July, where we looked at our genome sequencing program in a very similar way, where we sort of say, well, we understand what we've accomplished, but we're interested in the and beyond part. And we go into these workshops very open-minded to hear what the community is going to tell us, taking stock and thinking strategically about what we could do, either the same or what we could be different, or maybe that what we don't need to do anymore. And one of the other realities, of course, is that we need to think about these things that get discussed within sort of the context of other opportunities that are available and the Institute wants to pursue as well. And I'll ask any of the council members who are here during break, this is what we really are going to have to struggle with over the next couple of years because we are faced, obviously, a very tight fiscal circumstance, which we don't think is going to necessarily get better anytime soon. And yet the science just gets more and more exciting every year. So really, where we are, and the purpose of the workshop, is recognizing the end and getting near the end of the current funding phase of ENCODE, this third phase, we want to take stock. And we want to do this with a bunch of smart people like you. And our goal really is to then hear your thoughts and to really assess where the landscape is now, how our knowledge is advanced, what are the programs that exist that are doing complementary things, thinking about what should NHGRI do, maybe what should NHGRI not so much do, what are going to be picked up by other communities of researchers, what are the gaps that need to be filled. And then to help us think about the scientific questions and also explore a little bit about what's the right way to configure the kind of research that needs to be done and beyond part of this title. I'll also throw out there, again, I'm not telling you anything you won't hear about through discussions or pretty openly debated in lots of settings, but also our council is certainly very much engaged in discussions about this. And I think even NIHY, there's lots of discussions about this, and especially since our council meetings, the open sessions, or videocast live and video archive, lots of people watch in to hear some of the discussions, is just because a given program or a given approach for doing a genomics effort has been consortium-based and very top-down managed, the way we've done the first three phases of ENCODE, is that the right way to be doing it going forward? Or should it be some mix? Or should it be some other extreme? And so all these things are on the table, and certainly we're having lots of discussions internally and with our advisors about what is the right balance of top-down big projects versus investigator-initiated projects, and what should we be thinking about for any of our programs, what that mix might want to look like. It's not to say we're going to change things. It's just going to say we're going to always have that discussion. And I can certainly tell you that discussion is very much on the minds of our advisors who want to constantly explore the options for us and just making sure we're making optimal use of the resources that the institute has. So with that in mind, I think I'll just turn this over to Elise. I'll quickly scan across the group. Anybody has any questions? I'm happy to answer them. But if not seeing anybody with an immediate question, yes, Ervinda. Eric, I'm just wondering more about your thoughts and thoughts of the institute. Clearly, it was a point in time where almost everything was very heavily and correctly weighted to the genome biology. And now, obviously, you have many projects, funded projects that's actually very disease-specific. So increasingly, I would say. Let me just challenge you. Disease-specific or disease-oriented? Well, disease-specific. They're disease-oriented, I should say. Disease-oriented, fair enough. So the question is, increasingly, the real utility of one part or another part of any given genome biology needs to be tested with some examples. And of course, I'm not talking about mechanisms. So what's the thinking of how you transit from, I know your heat map and diagram, but the transition in between always, to me, it looks to be difficult to parse. Yeah, I'm not sure I can give you a crisp answer. I would say one of the things that I have personally, I think we, the staff, have found gratifying. I think you'll see at least one example of this is, I don't know if we've actually trademarked in code. I don't think we actually have. But it's interesting how many people are taking in code and using it coupling to another part. So you'll hear the second thing that I guess Mike is gonna talk about, a psych in code as one example. And there's others. And I know of at least a couple or a few other, actually I most recently heard about even moving outside of the biomedical community into the plant world, a similar use of in code for a genomic analysis of a particular type of plant. And so one of the things I find gratifying about that is that it gives a chance for this transition to take place from just basic kinds of things that in code is doing into a more disease or disease area focused realm that might make the transition you're talking about. It might not, but at least it's gratifying to see the value that people are seeing the potential value of helping to catalyze that transition happening in areas that they're very interested in. And I suspect, I think we'll hear probably from some others of other similar examples. One of the questions I guess I'd ask this group is, is there enough of those little seeds being germinated elsewhere in other community, other institutes or other communities so that we'll learn those lessons or is there no sign of that in which case it's something that NHGRI really needs to catalyze more? It's all this balancing act. Okay, yeah, right. I'll add on top of our Vindas point. I think certain types of biological functional knowledge is best collected in diagnostic view. But some aspects, and in particular, maybe I don't want to use the word functional, I think it's too general, but the physiological impact is very hard to collect agnostically. And I think that's going to be one of the big challenges we're going to grapple with in this meeting and well beyond it. Where does a completely agnostic view start failing in actually collecting the information that we want to collect? And I think that's separate from disease area and so on. And we struggle with that and talk about that a lot and we often will say, well, if we're not opposed to working on cancer, for example, I mean we went in 50-50 on the cancer genome atlas, we recognize that that was of great value. We're not against working on certain disease areas. We tend to say we will do that, especially if it's a model, if we will learn that, we'll tip our toe in non-disease agnostic waters, but we will do it if it's sort of at a model level, we'll learn some key lessons that could then be generalized. It's sometimes hard to make that assessment because is it a model or is it really a point that is sort of beyond what NHCR should be finding? There is not a bright line and I think we will always have to sort of feel our way through that and struggle with it. But of course the other approach is to convince other communities, other institutes, which is why it's wonderful, we have other institute representatives here that to see how they will benefit from the kinds of things being done in a disease agnostic way when you start to focus it on their disease areas and we're hoping that that uptake will be, and it's shown to be a success, we just want to see more of it. Okay, turn it over to Elise. Thank you very much.