 Okay. Thank you, Rudy. Let me also add my own welcome to the four new members of council. I look forward to working with you. I appreciate your willingness to serve on this important committee. I will also say at the onset it has been a busy handful of months since the September council meeting. So there is a lot that has poured in that we wanted to update you about. So bear with me because there's many updates we wanted to share with you. Now, as always, the open session of this meeting of the council is being webcast live, but in addition, we are videotaping it and making these recordings available as a permanent archive on the internet, including both the presentations that you're going to see, but also the associated documents. And for those who are new to my director's report and to council meetings, be aware that we have an electronic resource associated with my director's report that's analogous to a supplemental materials section of a published paper. This is the URL where you can go to to get to all sorts of associated documents. When there is, in addition to my presentation, which is available both as a PDF file and a PowerPoint file, we supplement many of the slides with electronic documents, websites, various other files we thought would be of interest. It's always indicated on the bottom right of a slide. And then this entire resource is archived permanently on our institute's website genome.gov as sort of a historic record of the meeting. Now, there's going to be several other presentations during the open session. In addition to my director's report, and I've tailored the presentation, my director's report around those presentations so that we're not too redundant. To begin with, later this morning, you'll be hearing from Dr. Terry Minolio, who'll give an update on the genomic medicine working group of this council. After lunch, Dr. Eric Borwinkel, also a member of council, will be giving a presentation on the Alzheimer's disease sequencing project. We'll then shift our attention for the majority of the rest of the open session and deal with a number of concept clearances. First, Joy Boyer will present a concept clearance for renewal of the Centers of Excellence in LC research. This will then be followed by a presentation of four concept clearances by Dr. Adam Felzenfeld, all relating to the renewal of the NHGRI genome sequencing program and, collectively, representing a continuation of the discussion of this renewal from the September 2014 council meeting. Specifically, these concepts will relate to the genome sequencing program analysis satellites, a genome sequencing program coordinating center, high quality human and primate genomes as foundational resources, and comparative and evolutionary genomics. So that will be the key concept clearance part of open session, and we'll then have two final presentations in the open session. Dr. Rongling Lee and Jacqueline Otis will give a biennial report on the inclusion of women and minorities in NHGRI supported research, and then Rudy Pazzotti will go over the review of the statement of understanding between the advisory council and NHGRI, and that will then wrap up our open session. So what I'm going to do now is follow these seven areas of my director's report, which continue to be an excellent framework for reviewing the necessary things that we want to tell you about starting with some general NHGRI updates. First thing I'd like to do is to call your attention to a new feature on NHGRI's website, genome.gov. Now, as you know, we have a very talented communications group at the institute, and a priority area for them is the use of video for telling NHGRI's story to the public and to the research community. And one example of this is the routine video casting and video archiving of the open session of these council meetings. But another important project that they recently completed and was debuted at this past fall's American Society of Human Genetics meeting was a slick new 15-minute video that tells NHGRI's story from the beginning through today. It's a silent form video, but in doing so it spotlights the institute's major programs and research areas across all the divisions and introduces the various components of the institute. This fast-paced video incorporates some rarely seen archival videos and photographs and really honors the pioneers and leaders that have contributed to the developing development and growth of our institute. It's also readily updateable, and so it's something that we plan to sort of add major programs as they come on board and launch them. And I encourage you to view this at some point when you have about 15 minutes. I mean, I really want to give a special shout-out and thanks to Alvaro and Sinis, who's our institute's videographer, who led a team of individuals to create this video-based story about NHGRI. In terms of leadership at NHGRI, in October, Ellen Rolfes was appointed the NHGRI Executive Officer and Director of the Institute's Division of Management. This is one of the institute's seven divisions. This appointment followed a rigorous national search. Now in this position, Ellen oversees all aspects of administrative management within NHGRI, including management analysis and evaluation, financial management, information technology, and human resources. She also serves as NHGRI's Deputy Executive Counselor. Over her impressive career at NIH, including 18-plus years at NHGRI, Ellen has worked in a variety of administrative management positions, most recently serving as our Deputy Executive Officer. While perhaps less well known to members of this council, Ellen is incredibly well known and well liked among the NHGRI staff because it is widely appreciated that she works tirelessly and effectively to ensure that NHGRI is the best administratively managed institute at NIH. There have been several other changes with respect to leadership positions, particularly within the Division of Policy Communications and Education. The first of which, as you heard from Rudy's introduction earlier, was the appointment of Dr. Bob Wilden as the Chief of the Genomic Healthcare Branch. Prior to joining NHGRI, Bob practiced clinical genetics in the Pacific Northwest in both private and hospital-based settings. In addition to his tenure as a medical faculty member at several hospitals, Bob has experiences as a consultant on biomedical informatics software and is medical director of a clinical molecular diagnostics laboratory, which should provide him a very unique perspective through which to advance the activities of this important branch. We look forward to Bob's leadership in expanding NHGRI support of educational resources and outreach to engage healthcare professionals and the public in genomics. This was a long search process, and in particular I want to thank Dr. Jean Jenkins for her efforts during this time to ensure that the branch's initiatives were not only maintained but expanded in scope and visibility, and I want to welcome Bob to the institute. Meanwhile, a valuable member of my leadership team has changed his role slightly at the institute. Vince Bonham was the founding chief of the Education and Community Involvement Branch, a role that he really served in brilliantly in leading the branch for about 10 years, but Vince recently stepped down as chief of this branch so that he could focus more of his time on two other major roles at the institute. Specifically, for the next phase of his NHGRI career, and Vince is going to spend more time on his own research within the intramural research program, social and behavioral research branch, as well as to devote more of his attention to his role as my senior advisor for genomics and health disparities. For the latter responsibility, he will assist me in steering NHGRI's research in the areas of health disparity and minority health, in particular by building bridges with other NIH institutes as well as the extramural and intramural research communities, and also by promoting genomics and LC research in the study of issues that are important to health disparities and minority health. With the shift, in Vince Bonham's role at NHGRI, we quickly launched a search for a successor to oversee the vibrant portfolio of activities underway in our education and community involvement branch, and I'm very pleased to report that last month we announced the selection of Dr. Carla Easter as the new chief of this branch. Carla served as the deputy chief of the branch for the last two years and has had an impressive career working with schools and teachers in developing science outreach programs for many years. And as deputy chief, Carla was instrumental to the successful development, launch, and ongoing tour of the Genome Unlocking Life's Code exhibition with the Smithsonian's National Museum of Natural History. So we're delighted to have Carla now leading this important branch of the institute and are confident that she will simply rock in this new leadership role. Finally, in terms of major NHGRI leadership positions, I want to make you aware of a couple of important recruitments that are now ongoing, starting with specifically the chief of the communications and public liaison branch, also part of our division of policy communications and education. Now, this branch chief serves as the overall communications director for NHGRI, working closely with Laura Rodriguez and myself in dealing with all aspects of the institute's communications programs. The chief manages and leads communications and media relations activities across the institute, as well as contributing to trans-NIH communications initiatives. This position is critical to achieving the institute's aim to disseminate, explain, and highlight genomics research to the broader research community and also to the public. With this mandate, this individual works in close collaboration with almost with all other parts of NHGRI, but also across NIH and in some cases the Department of Health and Human Services. So this is a very important recruitment for me and the institute, so if you have suggestions for outstanding candidates or wish to provide more information to a colleague, please let me or Laura know as soon as possible, and I provide here the relevant contact information for Laura Rodriguez. There's another important recruitment that we wanted to bring to your attention, specifically for a medical officer in the division of genomic medicine. That recruitment aims to help the institute foster the application of genomics for clinical care. This medical officer will work closely with Terry Nolio, Director of the Division of Genomic Medicine, to identify evidence gaps and research needs critical to the integration and application of genomic information and clinical care. Current programs closely associated with this division are familiar to this council and include the Emerge Network, the Caesar Consortium, the ClinGen Resource, the Undiagnosed Diseases Network, and the Ignite Consortium. Upcoming opportunities are being identified in collaboration with the NHGRI Genomic Medicine Working Group that you'll be hearing a summary about later in the open session. And future programs are under development in areas such as pharmacogenomics and evidence generation. Well, the JOB ad will hit our website and the USA JOB site on February 16th, but if you, you can already view ads in the New England Journal of Medicine, Cell, JAMA, and the American Journal of Medical Genetics. And if you have suggestions for outstanding candidates or you need more information, please let me or Terry know as soon as possible. And here I also provide contact information in this case for Terry Minola. Now, for the last general NHGRI update, I want to remind you that at the September Council meeting, I pointed out that the final NIH Genomic Data Sharing Policy was published on August 26th, 2014. Now, as of January 25th, just two weeks ago, all NIH intramural research projects as well as grant or contract applications that include funding for the generation of genomic data are expected to meet the expectations within the policy. Now, as Chair of the Internal NIH Oversight Committee for this policy and as Director of the Institute that has been a leader in data sharing practices for many years, actually dating back to the Human Genome Project, I'm committed to ensuring that NHGRI is a leader in implementing the genomic data sharing policy. So, over a year ago, I asked my staff and senior leadership team to begin planning and preparing for the consistent and fair implementation of the policy across the extramural research program and our intramural research program. And in addition to working on implementation of the policy within NHGRI, our institute staff members are coordinating with other NIH institutes and centers and participating in NIH-wide implementation activities so as to share our experiences and establishing processes, but also to learn from others and to leverage agency-wide developments. Now, this we fully recognize will be an ongoing process. At times it's going to be quite challenging, but I really regard this as one of the high priority areas for the institute. So, moving on to general NIH updates and it has been a very busy and exciting few months since the last council meeting with respect to the attention paid to NIH by very high level government leaders. So, for starters, in December, President Obama visited NIH for the second time during his presidency. He toured the NIH Vaccine Research Center. He also gave a speech to a packed audience in one of the auditoriums in the clinical center. In his remarks, the president praised the contributions of NIH staff in dealing with the ongoing Ebola crisis, including the care of Ebola-infected patients at the NIH Clinical Center. Now, unlike his previous speech at the NIH for this particular visit, the president seemed to want to work the room in at least the front of the room after his remarks concluded. And while I was sitting in the second row, I was not going to miss the opportunity. No way. I was going to miss the opportunity to shake the president's hand. Now, fortunately, what I lack in general athletic build, I make up with really, really long arms and really did help in situations like this. So, I got the shake. I got the shake. I got the shake. I haven't washed my hands since. No, but you could tell they were watching me. Pretty careful. So it didn't stop with the president's visit because then just two weeks ago, Department of Health and Human Services Secretary Sylvia Burwell came to NIH to meet with a small group of NIH leaders, including me, as shown on this group photo that was taken, to discuss a few particular topics of interest, including clinical applications of genomics. And while at NIH, the secretary also toured the NIH clinical center. She met with patients and she participated in a town hall meeting with the NIH staff, and I'll come back to that town hall meeting in a few minutes. But by far, the most exciting development relating to high-level government leaders and the NIH relates to a major new initiative recently announced by President Obama. Now, because of the importance of this initiative, especially for NHGRI, I thought that it was worth dedicating some of my director's report to describing the story behind the announcement and the current plans of this effort. Now, let me start to begin with. It's really important to remind you that President Obama has a long-standing interest in biomedical research, but in particular genomics. For example, in 2006, then Senator Obama introduced a piece of legislation in the Senate entitled the Genomics and Personalized Medicine Act. Now, while this bill was never passed, and in many ways is emblematic of the genuine interest that the President has in genomics and the opportunities to individualize approaches to medicine. And throughout his presidency, his interest in genomics has grown. This, of course, has been nurtured by people that he interacts with on a scientific topic, such as NIH director Francis Collins and also Eric Lander, as co-chair of the President's Council of Advisors of Science and Technology. For a number of reasons, this greatly intensified early last summer, eventually leading to a request from the President to bring him a plan for a bold new initiative that he could launch during the remaining two years of his presidency. Now, the President's interests have in fact broadened beyond genomics, and so we were asked to formulate our plan around the notion of precision medicine. And I think this broader context aimed to consider all elements that are relevant for individualizing medical care with the goal, of course, of advancing human health. And as you will see, NIH was not alone among federal agencies in developing such a plan, but that said a modest number of us from NIH work quietly and diligently throughout the summer and into the early fall developing a scientific plan for a possible presidential initiative in precision medicine. Now, our fundamental thinking about precision medicine was fairly simple and familiar to many of you. I mean, you know, today we tend to deliver medical care based on the expected response of the average patient, and yet we know that that is far from perfect. And eventually, meaning tomorrow, we want to deliver medical care based on individual genomic and environmental and lifestyle differences and that enable more precise ways to prevent and treat disease. Well, in developing a plan for an ambitious initiative in precision medicine, we focused on research areas that needed to be accelerated to basically get us from where we are today to this new tomorrow. And so a number of us developed a plan by the early fall, and it was presented to the president, who very much embraced it. It then went through the process of being readied for inclusion in the president's fiscal year 2016 budget and for its announcement by the president. We were told to expect some mention of the initiative by the president in his January 20th State of the Union address, but to be honest with you, we had no idea exactly what he would say. We were delighted to hear more than we actually had anticipated he would say, and I'll show that here. Twenty-first century businesses will rely on American science and technology, research, and development. I want the country that eliminated polio and met the human genome to lead a new era of medicine. One that delivers the right treatment at the right time. In some patients with cystic fibrosis, this approach has reversed a disease once thought unstoppable. So tonight, I'm launching a new precision medicine initiative to bring us closer to curing diseases like cancer and diabetes, and to give all of us access to the personalized information we need to keep ourselves and our families healthier. We can do this. A couple things to note. First of all, I watched the entire State of the Union address. It was one of the few times that both Boehner and Biden clapped at the same time. That was good. And also notice people standing up on both sides of the aisle, which is why I let the clip go a little longer. So that happened at the State of the Union address, and then ten days later, on January 30th, a couple hundred guests were invited to the east room of the White House for a formal announcement by President Obama, Council Member Bob Nussbaum. I was among the guests, as were a small number of us from NHGRI, and that announcement took place I was able to get a good center seat and took these photographs. And he sat among a number of very wonderful things in his announcement and that's why the budget I sent to the Congress on Monday, again this was all time to the budget release, will include a new precision on medicine initiative that brings America closer to curing diseases like cancer and diabetes and gives all of us access potentially to personalized information that we need to keep ourselves and our families healthier. So that was the announcement. But just as the President was announcing plans for the precision medicine initiative on January 30th, this was coordinated so that the New England Journal of Medicine published online this perspective, co-authored by Francis Collins and Harold Varmas, and if you haven't seen this I would encourage you to look at this paper provides an excellent summary of the general scientific rationale and the initial plans for the initiative. Now let me just give you a few more details about this I knew you'd be interested in this it's really worth stressing that the precision medicine initiative largely reflects ideas that have been considered before, in fact ideas that have even been discussed at this council. However it frames them in a new light due to some key developments that have occurred and particularly over the last decade. Now in my thinking I think there's really five areas that I describe this as sort of being significant with respect to advances that have taken place in the roughly the past decade that together really serve as the underpinnings for at least the early plans of the initiative. Those five areas are genomics, which I need to say nothing to this group in particular, spectacular the advances that have taken place in the last decade. Electronic health records, numbers that are certainly pointed out by the White House and by associated documents with the announcement were something like a decade ago maybe only about 20 to 30 percent of providers had electronic health records in place now that figures over 90 percent. That growth provides grand new opportunities. Obviously remarkable advances in technologies in particular and health devices such as shown here but also smartphones. The number of smartphones being used in the United States has gone up 160 fold in the last 10 years giving opportunities of communicating with individuals and having information collected on individuals behalf. Something very familiar with this council data science, biomedical big data and all the things we've discussed in recent years that genomics exemplifies as providing and really giving great challenges but also seeing some grand opportunities for integrating data across these various domains. But fifth and importantly final of course has been a shift in many ways with what I sort of describe as sort of patient partnerships. Just sort of we're finding ourselves in a new era. Some of it relates to having many more existing cohorts of individuals that are available for study but also I think social movements, the citizen science movement, the crowdsourcing efforts and so forth where patients really do and individuals, Americans, included wannabe active participants in research and through social media and other means and I think just cultural changes we have an opportunity to harness the energies and do things in ways that simply were not possible or we couldn't envision 10 years ago. So I think these five things very much have shaped the thinking that led to the precision medicine initiative as currently envisioned. It's currently envisioned as having sort of three major areas. First there's a near term effort that uses cancer as a model of precision medicine recognizing that cancer is the leading edge of precision medicine and yet there's so much more to be learned and that if we could simply ramp up current efforts very aggressively and expand it to more cancer types there might be some early wins that would clearly be of great benefit. Needless to say the National Cancer Institute will play a major role in leading this near term effort of this initiative. The longer term effort realizes that we of course want to expand this model to go to other diseases beyond cancer and in doing so that what the plan calls for the creation of a national research cohort of over a million volunteers and use that cohort in a productive way to generate the kind of knowledge base needed for advancing precision medicine. But also it was recognized that it wasn't just a matter of near and longer term research efforts but we also needed some policy changes. The initiative includes efforts to remove barriers to clinical implementation particularly related to federal rules protecting research participants but also advancing FDA's oversight of precision medicine products. So these are the three very broad stroke areas that are currently envisioned for the precision medicine initiative. Now as I mentioned earlier the timing of the president's announcement was tied to the rollout of the fiscal year 2016 fiscal year budget which includes a designated $250 million of new funding for the initiative within the president's budget and the proposed amounts of the relevant three federal agencies are shown here and you can see NIH with designated 200 million I can tell you that 70 million of that is for NCI and 130 million is for other mostly for the cohort at least as currently envisioned. I can tell you that one of the most gratifying and motivating aspects of the precision medicine initiative which was told to those of us involved in this for the past six to eight months over and over again is that President Obama's strong and personal interest in this initiative and the fields of study that it represents. Now you know we heard about this directly from Francis Collins many times but it was particularly interesting to hear Secretary Burwell describe this during her recent visit to NIH so she held a town hall meeting with staff and questions were submitted and one of the questions that she answered was as follows it was on all the lines of you work very closely with the president on a regular basis and and based on what you know about the president you know tell us a couple of things that would be of particular interest to NIH staff and here's what Secretary Burwell had to say. But with regard a couple things about the president two things that I think are important to know that could help you in your day-to-day work. The first one is and I'm sure you've told the team this the precision medicine thing that's him. This is like a presidential priority this is the amount of time that is being spent on this issue by the president of the United States relative to I could go through a whole list of issues is is incredible and so what you should know and what you should take from that is this is his own personal interest it is what you all do it is he believes so much that this is about our nation's innovation in science he believes this is about our economy he believes this is about the health and welfare of our people and so this while it's precision medicine it is a I think it gives you a view into his thinking about the work you all do every day so pretty remarkable again consistent with what we were being told not surprisingly since the announcement there's been considerable press coverage about the president's announcement with examples from the popular press shown here by and large it's been mostly good press as always some issues have been raised but I think by and large I think we're pleased with the coverage it received similarly there have been multiple stories published about the initiative in the scientific press I think similarly generally positive and encouraging about what has been laid out at least so far it's also important and gratifying to see that there is some early evidence that the precision medicine initiative while announced by the president will hopefully engender bipartisan support and to be successful we're going to need bipartisan support needless to say you know for example in this New York Times article Senator Cassidy Republican from Louisiana was quoted as saying this is an incredible area of promise he is a physician gastroenterologist but he did point out there will be bipartisan support and hopefully he can deliver that but at least there's a good signal of bipartisan support among the major elements of the initiative I just do want to stress and give a little bit more input about the middle one this cohort and particular because this is where NHGRI expects to be actively involved and in fact a number of us I counted up at least 10 of us have been involved at various levels throughout the summer and now in particular leading up to the announcement and what's going to take place later this week which I'll tell you about in a minute and there's been active involvement of a number of us and I'm sure that will continue although a lot of things are still not defined but let me drill just a little bit more about what's currently being envisioned for this national research cohort it is envisioned at least right now as having sort of something over a million U.S. volunteers these are not going to be all new individuals it really expects to take significant advantage of existing cohorts many of which have been funded by NIH but also recognize that that won't cover it adequately and so almost for certain we will need new volunteers to fill in gaps and make sure all the appropriate demographics are appropriately examined and considered and included the idea of course is to have participants share genomic data and lifestyle information biological samples importantly have all of this linked to their electronic health records which is again one of the reasons why now is so different than say 10 years ago the idea is and it has come out of discussions at this council the proceedings but also at workshops we have had that if you had such a cohort it would provide remarkable platform for all sorts of new studies to propel our understanding of health and disease but we don't want to just do it the way we've always done it and this is where I really do think that we want to develop new model or models for doing science that emphasizes engaged participants open responsible data sharing and of course ensuring strong privacy protections and from the earliest planning and discussions for developing such a research cohort it was recognized that new thinking and new ideas were going to be needed with respect to the participants and the data and the research sort of the three major columns on this slide I can tell you that for the participants the initiative will aim to develop new models for consent and recruitment of participants certainly with respect to data the data science opportunities created by the establishment of such a centralized database with the cohort you know especially in the areas of data integration I think you're going to be spectacular albeit with lots of challenges and finally for the research itself one can certainly envision building a new multidisciplinary scientific community centered on the cohort both to do very basic oriented disease discovery research but also to pursue more medically oriented studies related to clinical management and I would also point out that in each of these areas we've become aware of significant private sector interest in the initiative and so hopefully this will become a fertile area for new public-private partnerships and collaborations as well now we don't really pretend to have a detailed plan yet but we knew we were going to need to get to work very quickly following the announcement and so actually a couple of months ago we decided we would go ahead and schedule a workshop hoping that all the announcement would happen in time it all did but actually NHRI and NHLBI organized this workshop and invited people to it and now it's becoming basically an NIH workshop on behalf of the Precision Medicine Initiative and so this is a workshop that we've been working on behind the scenes for quite a number of weeks but specifically the two days after this council meeting later this week we're going to hold this workshop focused on building a large U.S. cohort the workshop will involve representatives from a wide variety of fields and domains including genomics, data science, electronic health records, mobile technologies, policy ethics law, epidemiology, patient groups, industry, government, and healthcare we had a great group of people coming since the announcement we've been overwhelmed with requests to come and unfortunately that's just not possible because of space constraints but nonetheless the discussions we fully expect to be quite important in shaping the early vision for this cohort we're going to include cohort identification and participant recruitment participant engagement data privacy and novel ways of returning information to patients and participants data collection including mobile health technologies and informatics and electronic health records now recognizing the interest in this and the incredible outcry of interest and additional people coming we are video casting this live and also video archiving the entire workshop for future viewing and I can certainly tell you that in addition to that we are going to make sure that we regularly update this council because we know that you're going to be very interested in as things play out if you want to read more there's now a dedicated website for the precision medicine initiative at the White House it has lots of things videos and various documents but in addition you might not be surprised to hear that we also launch one of the NIH which is really easy to remember in terms of its URL and it has lots of information already up there but notice there's a link right there to this workshop that's taking place later this week and if you click on that you will get to here and here you will see information on how to not only get to the video cast and eventually the video archives but already posted and they just went up over the weekend are four white papers that have been developed that will be the fodder for active discussion at the workshop and you could all get to those white papers and see them any time you want including now or certainly after my director's report okay so that's what I wanted to share with you about the precision medicine initiative and at the end of director's report happy to take questions that you might have so but again there's been a lot of other things going on since the last council meeting we finally have confirmed and now serving a new surgeon general Vivek Murthy who's now the 19th surgeon general in the United States he was co-founder of Doctors for America which focuses on advocating for affordable health care for all Americans and it's great to have a surgeon general of now in place last week there was a yet another development of relevance in terms of leadership within the Department of Health and Human Services the FDA announced that Dr. Margaret Hamburg the U.S. FDA commissioner is stepping down at the end of March after six years of heading the FDA and overseeing public health initiatives ranging from tobacco control and food safety to personalized medicine and drug approvals Dr. Hamburg's public health focus has been a hallmark of her career a constant champion for patients health during her time as FDA commissioner Dr. Hamburg was committed to fostering the growth of science and innovation across the agency and changing how the FDA and industry collaborate Dr. Hamburg leads a strong legacy of accomplishment at the FDA Dr. Steven Ostrov the FDA's chief scientist will serve as acting FDA commissioner and NHRI will continue watch you with keen interest FDA's involvement in genomics and its movement into the clinical sphere at the NIH level there's some leadership changes going on as well late last year Don Lindberg announced that he will be retiring from federal service at the end of March Don has served as director of the National Library of Medicine for more than 30 years during his tenure he led the library's transition into the electronic informatics age and oversaw numerous landmark projects including the launching of the Medline database via PubMedClinicalTrials.gov the unified medical language system and a particular relevance to the field of genomics and NHGRI the National Center for Biotechnology Information NCBI well when Don departs deputy director Betsy Humphries will step up and serve as acting director of the NLM now while Don Lindberg leaves behind an icon of an organization at the NIH nonetheless the National Library of Medicine has been a center of information innovation since its founding in 1836 but at the same time lots of things have changed with respect to how health information and biomedical information are collected, shared and analyzed and we've also shifted from largely print to largely digital media and we really are seeing ourselves transitioning into a data intensive era and so NLM's role really probably needs to evolve to continue meeting the many challenges in information and data science and so rather than immediately launching a search for a new director of NLM NIH director Francis Collins has decided to first pause and strategically consider the role that NLM should play in the current and future biomedical research enterprise and so to carry out a renewed visioning process he's established a working group of his advisory committee to the director or ACD now I was actually asked to co-chair this working group along with ACD member Harlan Krumholz of Yale University the working group is charged with reviewing the mission organization and programmatic priorities of the NLM and articulating a strategic vision for the NLM in order to ensure its continued leadership in the field of biomedical and health information specifically the working group will address how the NLM should continue to meet the rapidly evolving scientific technological needs of the biomedical community by developing and adopting information technologies providing growth of the open access movement maximizing usefulness and cost efficiency of NLM's archives and interfacing with NIH's broader efforts to address major data science challenges facing biomedical research the working group is on a short timeline though and we have to present our final report for consideration at the June meeting of the ACD I would also point out that a website has now been established that contains all the relevant information about the efforts and products of this working group and I would certainly be interested if council has any ideas or input to the process we would greatly value that as the working group is now getting quite active another working group of the advisory committee to the NIH director recently finished its evaluation of the national children's study a large attitudinal observational study examining the effects of a broad range of environmental and biological factors on children's health and development the study was envisioned to follow 100,000 children from womb to age 21 the working group concluded that quote the overall goals of examining how environmental factors influence child health and development are meritorious and should continue to be a priority for future scientific support but the national children's study is currently designed is not feasible end of quote the NIH director has agreed with this assessment and has moved forward with the cessation of the national children's study data and resources produced from early pilot efforts will be made available to the research community one of the 27 NIH institutes and centers recently underwent a name change per language included in the fiscal year 2015 budget the national center for complementary and alternative medicine or NCAM was recently changed to now be the national center for complementary and integrative health or NCCIH the new name more accurate reflects the center's mission and research agenda other leadership updates Dr. Kerry Wolinitz has been named and appointed the new NIH associate director for science policy and is also the director then of the NIH office of science policy she comes to NIH from the association of American universities where she served as deputy vice president for federal relations primarily working to coordinate advocacy on funding and policy issues relating to NIH and biomedical research she also serves as the current president of united for medical research and is an adjunct assistant professor at Georgetown University now Kerry takes over for Dr. David Sherlock who took on the role of acting associate director for data science after Dr. Amy Patterson became the associate director for biosecurity and biosafety policy a good friend of NHGRI's Judy Greenberg was recently appointed the deputy director of the national institute of general medical sciences NIGMS she has a long record of dedicated service to NIGMS and NIH including two extended stints as acting director of NIGMS so congratulations Judy now in terms of activities within the U.S. Congress in my September directors report I described how the energy and commerce committee of the House of Representatives led by chairman Fred Upton and representative Diana DeGette had launched the 21st century cures initiative in June of 2014 I also noted that the committee held multiple roundtables and hearings around the country of one of which I participated in in Colorado to solicit suggestions about the role that Congress could play in accelerating the pace of scientific discoveries and their translation to treatments and cures now the committee had previously indicated it would introduce legislation based on the feedback it received and accordingly on June 27th it released a discussion draft of legislation entitled the 21st century cures act now the draft bill at nearly 400 pages contains numerous provisions affecting NIH specific to genomics there are placeholder sections called precision medicine not surprisingly and modernizing regulation of diagnostics but no proposed bill language is there yet and while the draft bill was released by chairman Upton it does not yet appear to have bipartisan support based on a number of news stories but nonetheless committee democrats continue to express their hope for a bipartisan consensus on the bill on the senate side of things the senate health education labor and pension or help committee chairman Lamar Alexander and senator Richard Burr recently released a report detailing their plans to assess the impact and efficiency of the FDA and NIH entitled innovation for healthy Americans the report details their perceptions of the inefficiencies of the integration of new medical discoveries in the patient care the senators will be soliciting feedback on the report including through a series of hearings as they begin to examine the time and cost currently involved with the drug and medical device discovery and development processes as well as how public policies could be better aligned to support medical innovation now the jurisdiction of the senate help committee is similar to that of the house energy and commerce committee and there are many similarities between this report and the issues of the 21st century cures initiative is seeking to address but of course to become law the 21st century cures act will have to be approved by both chambers of congress and the report from the help committee shown here is a way for the senator contribute its own proposals to the discussion now representative Upton has set the goal of congress sending a bill to the president by the end of 2015 whoever Lamar Alex senator alexander is not indicated whether he shares this goal or not so we are obviously watching all of this closely because of its obviously a potential impact on the precision medicine initiative specifically but also on the NIH more generally of course all of this is then relevant to budget matters and with the passage of an appropriation package dubbed the cromibus bill in December at least we now have a budget for this year so we now know NIH is an NHGRI fiscal year 2015 budget which is indicated in the middle column so out of NIH is 30.3 billion dollars NHGRI is a little over 499 million it increased about 0.3 percent over fiscal year 2014 which is shown in the far left so of course that's this year's budget all this discussion in both chambers of congress relate to next year's budget so the focus now shifts to establishing funding levels for next fiscal year so accordingly last week if I talked about it already a little bit the president has sent his fiscal year 26 budget proposal to congress and that's indicated in the far right column the president's budget requests 31.1 billion dollars for NIH including that 200 million dollars I told you earlier for the precision medicine initiative NHGRI would receive 515 million dollars which would reflect a 3.2 percent increase over the current year of note NHGRI's congressional justification or CJ as we once refer to it is available now on genome.gov with a direct link provided under document 17 now within the CJ if you want to review it you can find both a narrative explanation for the major NHGRI programs as well as a breakdown of how the institute anticipates allocating dollars requested by the president if received well congressional groups will now examine this proposal through hearings but at the same time before we know we're going to have a long wait before we really know when NIH or NHGRI's final fiscal year 26 budget is actually going to look like however looking at all the recent attention in interest at the highest levels of the administration also seemingly both chambers of congress particular about the opportunities with genomics it's clear that our field of interest is going to be a significant part of the conversation in the weeks to months to come which is actually a good thing so let me move on then away from NHGRI NIH updates now start focusing on genomics updates starting with a recognition that a genetics legend Mary Lyon passed away in December Mary developed the idea of X chromosome inactivation a process that came to be known as lionization in honor of her theory late last year President Obama awarded the National Medal of Science to Bruce Alberts and the National Medal of Technology an innovation to NCI's own Doug Loewe and John Schiller these awards are our nation's highest honors for achievement and leadership and advancing the fields of science and technologies and these honorees are all good friends of NHGRI another good friend of NHGRI Mary Claire King was recently awarded the Lasser-Kochland Special Achievement Award in Medical Science for her bold, imaginative and diverse contributions to medical science and human rights Mary Claire played an instrumental role in the discovery of the BRCA1 gene associated with hereditary breast and ovarian cancer and also deployed DNA strategies to reunite missing persons or the remains within their families The American Society of Human Genetics gave awards to three members of our community at their 2014 annual meeting in San Diego First, Dave Alley was a 2014 recipient of the Victor Amy Kuzik Leadership Award for professional achievements that have fostered and enriched the development of human genetics as well as its assimilation into the broader context of science, medicine, and health and Gonzala Abacasis and Mark Daley were the 2014 recipients of the Kurt Stern Award for significant genetics and genomics scientific contributions during the past decade Congratulations to all of them Other prizes The Breakthrough Prize in Life Sciences recognizes excellence in research aimed at curing intractable diseases and extending human life of relevance to genetics and genomics The 2015 Breakthrough Prize Life Sciences was awarded to Jennifer Douda and Emmanuel Charpenter for their work on CRISPR-Cas9 In addition, Gary Ruffkin and Victor Ambrose were honored for their exploration of microRNA-based gene regulation Other honors included the Institute of Medicine who recently announced their newly elected members and of relevance to our community A new member is included, Gonzala again Todd Gallop, Julie Johnson, Harry Orr, and Joe Takahashi Congratulations to all of them And similarly, an impressive field of individuals from our community were recently elected as fellows of the American Association for the Advancement of Science or AAAS The names are listed here Congratulations to all of them as well We could continue tracking the movement of genomics notables One of which was Hunt Willard was recently appointed the new director of the University of Chicago Woods Hole Marine Biological Laboratory Congratulations, Hunt And many of you probably have heard that David Alschuler has joined Vertex Pharmaceuticals as executive vice president of global research and chief scientific officer So congratulations to David as well Moving from people to institutions and certainly of interest to Carol Bolt, a member of this council Last October, I was invited by Ed Lu and Charles Lee to participate in the ceremonial opening and ribbon cutting for the Jackson Laboratory of Genomic Medicine I also spoke at their opening scientific symposium The Jackson Laboratory for Genomic Medicine is a non-profit research center that identifies the precise genetic causes of diseases and spurs the development of individualized plans of treatment and prevention With 150 employees higher to date the 184,000 roughly square foot facility expects to house about 300 biomedical researchers, technicians, and support staff over the next 10 years It is an impressive facility and it was fun to participate in their opening events When the scientist came out with its top 10 innovations of 2014, genomic technologies dominated the list In fact, each of the top five innovations on their list involved some aspect of the process of genome sequencing These include the Dragon Bio IT processor by Itaco Genome Illuminous MySeq DX Illuminous HighSeq X10 system The IrisChip V2 by Bionanogenomics and the Raindrop Digital PCR system by Raindance Technologies All pretty impressive Featured as an NHGRI genome advanced the month since the last council meeting have been publications describing the genomic origins of the 2014 Ebola outbreak Artificial sweeteners and the gut microbiome Genetic adaptation of the human circadian clock Super centenarian genomics and most recently DNA testing to detect cancer precursors in blood Recent prominent genomics in the news stories include a Forbes article about cancer genome testing An article in the New York Times about the funding climate for young scientists A Wild Street Journal piece on newborn genome sequencing A reported genome web regarding Google's plans to cover cancer genome testing for its employees And lastly an article in the scientist about council member David Page shown here and his remarkable research career studying the Y chromosome Congratulations David And in terms of genomes in the news as always is a number of newly generated genome sequences reported since the last council meeting including the oxytrichid germline genome The Glanville Fritillary butterfly Gibbon 16 Anopheles species The House Fly A modern human man who lived in Siberia 45,000 years ago A snub-nosed monkey Koala Barrett Orchid Centipede Four species of mudskippers The bowhead whale Multiple cat genomes and literally a flock of different birds So as always comparative genomics active as could be So moving on then let's go through some major summaries of our extramural research program Now following the discussion at the September council meeting about renewal of our genome sequencing program and approval of two initial concepts NHGRI released two RFAs in mid-December One RFA is for the new Centers for Common Disease Genomics Program while the other is for the continuation of the Centers for Mendelian Genomics Program Now these are the first two RFAs associated with what will be the new NHGRI genome sequencing program For these two published RFAs NHGRI will host an applicant information webinar on February 18th and then the submission deadline for both RFAs is April 7th Now later in this open session you'll be hearing additional concepts presented that reflect several additional proposed components of the new NHGRI genome sequencing program In terms of recent developments with our current program the large-scale sequencing analysis centers of course that's the largest component of the current program seek to address major biomedical questions by conducting very large genome sequencing projects For example, the Center's publisher submitted 54 new papers in the most recent quarter reflecting projects across a range of areas including the microbiome comparative genomics inherited disease cancer and technology development One of their larger recent projects is the Alzheimer's disease sequencing project that Council Member Eric Borewink will be making a presentation about later in the open session Of course, another major focus of these large centers has been finishing up the cancer genome atlas or TCGA Exome sequence data production was completed in January 2015 However, analysis continues in the project to schedule to officially end in spring of 2016 This graph on the left shows the number of tumor normal pairs with exome sequencing data broken down by cancer type The sequencing data was generated with over 10,000 tumor normal pairs and is publicly available in the cancer genomics hub or CG hub The other genomic characterization data is available through the TCGA data coordinating center Now, tumor-specific analyses remain a major focus for the TCGA Now, for each of over 30 cancer types the TCGA network plans to publish a comprehensive integrative analysis of genome sequence and mutation data also copy number variation gene and microRNA expression and promoter methylation The table shown on the right shows the status of TCGA publications and they're currently an additional 15 analysis working groups actively involved in preparing publications The TCGA paper on papillary thyroid carcinoma was published in cell in October and then the head and neck squamous cell carcinoma manuscript was published and feature on the cover of nature in January as shown here Second major component of our genome sequencing program the Centers for Mendelian Genomics was established three years ago now with the aim of finding the genomic cause of as many Mendelian conditions as possible To date, these centers have been responsible to discover over 600 causal genes from Mendelian conditions and some of those discoveries have been reported in over 125 publications Now, these centers also undertake a number of activities to facilitate project coordination and collaboration and to avoid unnecessary duplication of effort So, for example, they publicly post their joint project list at the program's website an example of which is shown on the right and they update that list regularly and this list is downloadable and includes Mendelian conditions that have been investigated and the conditions that are being investigated by the centers and their collaborators It is also annotated with OMIM numbers the center site at which the project is being performed and whether or not the center is interested in getting additional cases or not and the list currently includes close to 1,000 Mendelian conditions Another service offered by the Centers for Mendelian Genomics program aims to enable connections between clinicians and researchers from around the world who share an interest in the same gene or genes particularly when a gene phenotype relationship is not yet completely established So, towards that end the Baylor Hopkins Center has developed the software tool Gene Matcher which has been freely available since December of 2013 and at this site, investigators can post information about genes of interest and in turn be connected with other investigators who post information about the same gene Now, Gene Matcher has been used by a rapidly growing community of researchers since its launch For example, this bar graph shows the number of submitted genes submitted investigators submitting countries and successful matches made by last August 2014 in the darker color and also in January of this year in the lighter color So, for example, by January 108 matches have been made out of the 1493 genes that were submitted by 251 investigators from 29 countries and it's expected that many of these matches will lead to a productive collaboration on finding the causal gene for particular Mendelian condition of mutual interest The third component of our genome sequencing program is, of course, our genome sequencing our clinical sequencing exploratory research or CSER program This focuses on the integration of genome sequencing into the clinical workflow including the generation, interpretation and reporting of genomic information CSER has now enrolled over 3,000 adult and over 700 children as participants Over 2,600 of whom have had germline genome sequencing data generated and over 500 of whom have had tumor genome sequencing data generated Two recent papers highlight the diversity of data being generated by CSER investigators In a genome research paper that is just out online CSER's Actionability Returnal Results Working Group reviewed the interpretations of 663 genomic variants from 6,500 individuals and concluded that the rate of secondary findings in individuals is about one to two percent depending on ancestry This work highlights future opportunities to improve genomic variant interpretation In a second paper investigators at the University of Washington developed a decision modeling framework and shown here graphically for assessing the clinical and economic impact of returning secondary findings Incremental cost-effectiveness ratios range from 45,000 to 115,000 per quality-adjusted life years gained depending on the clinical context The CSER outcomes and measures working group is expanding work on the cost-effectiveness of clinical sequencing and organizing cross-site analyses As one measure of overall impact CSER has generated over 130 publications including nine working group publications To date CSER work has been featuring over 200 presentations and posters including at several recent national meetings and roundtables For example, CSER was prominently featured at both the American Society for Human Genetics and the American Society of Bioethics and Humanities in October of both meetings in San Diego In total, there were 30 CSER posters and 19 CSER talks at these two meetings In addition, the Institute of Medicine held their 20th roundtable meeting on translating genomic-based research for health in January and Washington, D.C. At that meeting, CSER investigators reported on the incidental findings and evidence assessments for return of results from genome sequencing The final component of our current genome sequencing program the Genome Sequencing Informatics Tools or GSIT program is known publicly by the name ISEEK Tools The program is comprised of six projects that develop approaches to provide researcher-friendly sequence analysis tools The program has developed a method to combine and evaluate multiple variant calls produced by different prediction tools making this challenging task easy and reliable for users Specifically, ISEEK Tools provides GKNO pronounced no pipelines that integrate results from multiple variants or mutation callers specifically by performing graph realignment of the various calls to resolve the different predictions This allows users to take advantage of the strengths and multiple variant prediction methods and converge on the most reliable results In this example, a unified prediction is made from Washington University, Broad University of Utah and University of Michigan variant callers Variant calls from Pindell, GATK and Freebase are combined and then realign to a graph reference and that allows them to be recalled more robustly and the same approach can be applied to mutation calls Now, easy to use genome analysis tools are also being provided as visualization apps on the web similar to apps on a smartphone A growing collection of these apps called iobio apps are available for easy real-time visual analysis of genomic data Well, moving on beyond our genome sequencing program following a one-year break from its annual gathering the advanced DNA sequencing technology development program will hold a grantee meeting in San Diego in May After the one-day grantee meeting there will be a meeting open to the public Participants will share their latest progress on DNA sequencing, technology development and ongoing challenges to further reduce the time and cost of sequencing whole genomes while improving data quality The goal of the Encyclopedia of DNA Elements or ENCODE project is to create a catalog of all functional elements in the human and mouse genomes and to make those catalogs available as a resource to the biomedical community NHGRI will be holding a small planning workshop entitled from Genome Function of Biological Insight ENCODE and Beyond in March And the goal of this workshop is to obtain community input on possible future scientific directions in the area of genome function following the conclusion of the current phase of ENCODE in 2016 The outcomes of this workshop will be discussed at the May meeting of this council Meanwhile, the annual ENCODE consortium meeting will also be held in March At that gathering, ENCODE members will present updates on their project and discuss ENCODE publication plans emphasizing the importance of releasing high-quality data to the community in the form of encyclopedia of candidate functional elements And ENCODE is also planning a community meeting a users meeting which will take place in late June consortium members will lead hands-on workshops on how to use ENCODE data while community members will be invited to make presentations on how they are using ENCODE data The users meeting is open to any scientist interested in using ENCODE data although registration is not yet open In terms of ENCODE publications the ENCODE funded publication list includes over 370 papers by the ENCODE consortium participants and over 148 publications by MOD ENCODE consortium participates collectively depicted by the purple parts of these graphs that you see are the bars There are at least 686 community publications from groups using ENCODE data but without ENCODE funding and at least 165 community publications from groups using MOD ENCODE data but without MOD ENCODE funding and those are collectively depicted as the blue part of those bars Some of you might have seen the mouse ENCODE which is funded as a separate entity initially with AERA funds from about 2009 to 2012 but this group recently published an integrative paper featured on the cover of Nature in November that compared DNA elements in the mouse and human genomes In addition to that nature paper there were nine companion papers that were also published in a number of journals including Nature Genome Research PNAS and Science New to sort of our genome function world at the institute is this new program the Genomics and Gene Regulation Project and the goal of this GGR project as we refer to it is to learn how to derive predictive gene regulatory networks starting from genomic data and in January NHGRI issued five awards totaling more than 28 million dollars over three years With these new grants researchers will study gene networks and pathways in different biological systems including the immune system skin and nuclear hormone receptor response The resulting insights into the mechanisms controlling gene expression may ultimately lead to new avenues for developing treatments for diseases affected by faulty gene regulation Moving on to our Centers of Excellence in Genomic Science or SEGs program two new SEGs awards have been made The goal of the SEGs at Stanford University is to develop technologies to interrogate interactions of the genome with its regulatory proteins and non-coding RNAs integrating variations in DNA sequences in chromatin states over time and across individuals and using small samples to capture genome-wide information in a clinical workflow The new SEGs at Harvard Medical School will build from an existing neuropsychiatric biobank to develop and use bioinformatics and cellular neurobiology tools along with assessment of cognition and other phenotypes to understand the cross disorder mechanism of action of disease liability genes The SEGs is being largely funded by our SEGs partner the National Institute of Mental Health and IIMH The SEGs annual grantee meeting was hosted in October by Aviva Gev and colleagues of the Broad Institute and it was another productive gathering of these grantees And finally recent SEGs grant applications will be discussed later during the closed session of this council meeting New SEGs applications meanwhile are due in May and it's not too early for potential applicants to contact program staff After nearly eight years of service the Trans-NIH Genetic Association Information Network Data Access Committee called the Gain DAC has been retired and the 10 data sets have been moved to the relevant other NIH DACs Now the Gain DAC was one of the first NIH data access committees established and it played a significant role in helping to shape the implementation of the GWAS data sharing policy and the DB GAP access process During its eight years of service the Gain DAC received nearly 1,700 project requests from 878 U.S. and international investigators from academic institutions not-for-profit organizations and companies and the cumulative pace of such requests since 2007 is shown in the bar graph For all their hard work we're extremely grateful to members of the Gain DAC including the chair for the past eight years Ann Ramos and all current and former members of the group for serving and also for Katya serving as a program analyst and the entire DB GAP team The NHGRI GWAS catalog is a curated downloadable user friendly resource that catalogs the findings from published genome-wide association studies Produced in collaboration with the European Bioinformatics Institute this past quarter the GWAS catalog team cataloged its 15,000th variant and 21,000 a 2100th paper Beginning in March the GWAS catalog content and search interface will migrate to the European Bioinformatics Institute under the leadership of Helen Parkinson and Paul Fleisig recipients of a recent U41 grant to make further informatics and curation improvements to this widely used resource Catalog users are being alerted to this transition on the NHGRI GWAS catalog home page and can sign up to receive email updates about the transition Now the EBI GWAS catalog page is currently under development it will be linked to the NHGRI GWAS catalog home page as soon as it is available Investigators in the Emerge Network leverage data from large biorepositories linked to electronic medical records to conduct genomic discovery and clinical implementation research In the final year of its second phase the network is actively disseminating its products and best practices among the broader scientific community As part of the Emerge PGX project investigators are collecting sequence data for 82 pharmacogenomic genes from a target cohort of 9,000 subjects The network has been cataloging variants and the related information on its publicly available web-based resource Sphinx To date Sphinx includes information about nearly 5,000 unique samples and nearly 26,000 variants associated with 60 pathways and relevant information for 515 drugs At the American Medical Informatics Association Symposium in November Emerge investigators received a Distinguished Paper Award for Electronic Phenotyping and the Homer R. Warner Award for their exportable software that protects biobank participant privacy Emerge will also lead two panel discussions and three workshops of the upcoming meeting of this group Translational Bioinformatics and Clinical Research Informatics Summit sponsored by this association that's going to be held in March of this year The consensus measures of phenotypes and exposures of Phoenix project has produced an online research of standard measures related to common diseases phenotypic traits and environmental exposures Use of Phoenix measures facilitates combining data from a variety of studies that makes it easier for investigators to expand a study design behind the primary research focus As a result of NIMH-funded supplement to this U-41 cooperative agreement Phoenix developed a new collection of measures focused on suicide and post-traumatic stress disorder These measures were released in the toolkit in December of 2014 The interest in the Phoenix process and toolkit continues to grow and so NHLBI, for example, has provided funds to launch a new sickle cell disease working group and the working group is just getting off the ground and measures will be developed over the next year And then lastly, Phoenix has worked closely with Vanderbilt's RedCap database team to make the standard protocols from three Phoenix domains available in RedCap The group plans to make five monthly releases in 2015 for the remaining 18 domains The Phoenix library will have a total of 429 protocols and are expected to become the biggest library in RedCap The population architecture using genomics and epidemiology or PAGE program focuses on identifying and characterizing genomic variants associated with common disease in ancestrally diverse populations PAGE investigators in collaboration with Lumina and the consortium on asthma and African ancestry populations in the Americas Consortium recently designed a large-scale 1.7 million marker multi-ethnic genotyping or mega array that facilitates discovery of genomic variants in multi-ethnic populations Building upon existing resources such as the African diaspora power chip and previous human core and human exome arrays PAGE investigators added a more robust multi-ethnic GWAS scaffold based on the thousand genomes project data functional variants drawn from a databases such as ClinVar and OMIM and new exomic variants based on 36,000 multi-ethnic exome sequences as well as additional custom content around loci relevant to PAGE-related traits and the array is being made available to the scientific community for improved characterization of non-European ancestry samples at a cost of about $75 each The purpose of the clinical genome research or ClinGen is to create a centralized repository and interconnected resource of clinically relevant genomic variants for both the clinical and research communities ClinGen investigators are working closely with NCBI and clinical laboratories to standardize the clinical assessment of genomic variants and the process of submitting them into the ClinVar database and as shown here there has been a steady increase in submissions to ClinVar In fact, as of January of this year there are over 129,000 genomic variants represented in ClinVar Now ClinGen recently launched a patient portal called Genome Connect patients enter phenotypic information and genetic testing reports to Genome Connect through the Patient Crossroads registry platform and have the option to connect with researchers and other families and individuals with the same genomic variant or variants And then in May of this year ClinGen will host a large public meeting with the Sanger Institutes group that oversees decipher the database of chromosomal imbalance and phenotype in humans using ensemble resources decipher ClinGen is looking forward to forge an international collaboration focused on the curation of genomic variants with this group The newborn sequencing and genomic medicine and public health are end-site program will explore in a limited but deliberative manner the implications, challenges and opportunities associated with possible use of genomic sequence information for the care of newborns The four sites held the inaugural end-site steering committee meeting in September at which key personnel from each of the sites discussed progress and network-wide projects Additionally, in December investigators from the Children's Mercy Hospital site published a paper in Science Translational Medicine describing their experience in using exome and genome sequencing to diagnose neurodevelopmental disorders in children including newborns within their neonatal intensive care unit For nearly 50% of the cases a change in clinical care or impression of the pathophysiology was reported Moving on to genomics and society issues and programs the Genomics and Society Working Group of this Council is charged with providing advice on short and long-term planning and priority setting for the Genomics and Society activities of the Institute The Working Group will hold its next in-person meeting in April As the Working Group enters its third year the founding members are starting to reach the end of their terms So I'd like to thank outgoing members Tim Caulfield Jeff Long Andrea Pantanoad and David Williams I greatly appreciate their service to the Institute And at the same time I want to welcome Council members Shanita Hughes-Halbert Barbara Bernhardt of the University of Pennsylvania and David Benstra of the University of Washington all of whom will be joining the Working Group Finally, after successfully leading the Working Group since its inception in 2012 Pamela Sankar will be stepping down for her role as chair and current Working Group member Lisa Parker as agreed to serve as the next chair and my thanks to both of them for continued contributions to this important Working Group In December NHGRI issued a notice announcing an expansion of its participation in the Ruth L. Kirsten National Research Service Award and the RSA Institutional Training Grant Program So as to accept applications focused on training the next generation of LC researchers The goal of this initiative is to support training experiences that provide an opportunity for pre and postdoctoral training that provide an opportunity to develop multidisciplinary conceptual and methodological skills necessary to pursue independent careers as an LC researcher And the first applications for this are due in late May for possible funding in the spring of 2016 In terms of our Centers of Excellence in LC Research or SEAR program the first regional SEAR networking meeting for trainees and investigators is being held at the University of Washington in late February The purpose of this meeting is to provide a more sustained training and networking experience for trainees associated with SEARs in the western half of the country many of whom are unable to travel to the annual meetings that are typically held on the east coast The next annual gathering of SEAR investigators will be held in March in Baltimore And finally a concept clearance for the next request for applications or RFA for the SEAR program we discussed later in the open session of this council So that gets us through our extramural research program Let me just now touch on Common Fund and TransNIH efforts of interest Starting with the Human Microbiome Project which is now in its phase two and it's which is also known as integrative HMP or IHMP to reflect its goal of producing integrated multi-omic data from DNA RNA protein and metabolites from the host and microbiome with the resulting data set serving as a community resource Now the IHMP marker paper which describes the data being produced in three longitudinal cohort studies of preterm birth inflammatory bowel disease onset and type 2 diabetes onset was published as an open access paper in cell host and microbe in the early fall The NIH Common Fund provided an additional $5.75 million to support an IHMP data coordination center which will be hosted at the University of Maryland and the second annual IHMP consortium meeting will be held in June of this year in Bethesda while the fifth International Human Microbiome Consortium Congress will take place in March in Luxembourg and over 500 participants are expected this latter gathering including 60 invited speakers representing 13 countries from four continents The Knockout Mouse phenotyping project Comp 2 is funded jointly by the NIH Common Fund and 18 other NIH institutes and centers It was launched in 2015 I mean 2011, sorry with the goal of making and phenotyping 2500 mouse knockout strains over five years Comp 2 investigators met with their international mouse phenotyping consortium partners at their annual meeting in November The meeting was intense with the first day involving a data update involving 150 consortium members and the second day involving summary presentations and feedback sessions with a panel of scientific consultants The Comp 2 program team has developed an agenda for a focus group meeting in March to help develop a proposal for renewal of the Comp 2 program for a second five years of support by the NIH Common Fund And finally, in light of a new policy on including sex as a biological variable and research design the current phenotyping data from Knockout Mouse was analyzed for sexual dimorphism preliminary analyses reveal that approximately 10% of phenotypes show this effect and the Comp 2 data was presented to the NIH office of research on women's health in November and is the subject of ongoing analyses Moving on to another Common Fund project Lynx aims to create a network-based understanding of biology by cataloging changes in gene expression and other cellular processes that occur when cells are exposed to a variety of perturbing agents Now, Lynx uses computational tools to integrate this diverse information into a comprehensive view of normal and disease states that can be applied for the development of new biomarkers and therapeutics The Lynx pilot phase has concluded and phase two awards were made shortly after the September Council meeting This included the funding of six data and signature generation centers and one NIH-initiated joint BD2K Lynx data coordination integration center The first Trans Lynx meeting involving investigators in all of these centers was held in October after which the external scientific panel generated a report on the program's progress All of the centers have now developed milestones for release of data and tools And finally, an announcement has now been published about the data coordination integration center's plan to solicit and support several specific short-term data science research collaborations These aim to enhance interactions between outside investigators and Lynx as well as to bring the novel expertise and analytical capabilities to the Lynx program H3Africa's central goals to develop a sustainable and collaborative African genetics and genomics research enterprise The fifth H3Africa consortium meeting took place in November in Tanzania Highlights included the presence of trainees and study coordinators at the meeting with a well-attended grant writing workshop and study coordinator led discussion session The meeting was actually preceded by an NHLBI-sponsored sickle cell disease workshop that attracted about 145 participants from 18 countries H3Africa has been given supplemental funds to perform whole genome sequencing of more than 300 samples with resulting data used to design a pan-African custom genotyping chip that will be put into production in May of this year And a supplement was given to develop a genetics and genomics training module for research ethics committees in Africa Topics will include informed consent community engagement and data and sample sharing Meanwhile, recent H3Africa publications include proceedings from the May ethics meeting as well as a letter to the editor of The Scientist by Francis Collins and Jeremy Farre who's the head of the Welcome Trust responding to an article criticizing the lack of basic science research funding for African scientists And this letter discussed how H3Africa is a prototype example of an effort aiming to address this problem Finally, the next H3Africa consortium meeting will be held in May in Zambia and this will then be followed by a consortium meeting in October of this year in Washington DC which will be held immediately after the annual ASHG meeting in Baltimore The NIH Common Funds Undiagnosed Diseases Network or UDN aims to improve the level of diagnosis and care for patients with undiagnosed diseases facilitate research into the etiology of these diseases and create an integrated and collaborative research community to identify and share improved options for optimal patient care In September, Baylor College of Medicine and the Medical College of Wisconsin were awarded UDN sequencing core grants to provide centralized genome sequencing for the UDN These two cores will provide clear level exome and genome sequencing data and clinical reports generated from patients and family members The full set of different network sites is also shown here on this graphic The UDN investigators held a steering committee meeting in November and key personnel from each of the 10 network sites were in attendance to ratify new chapters and the network's manual of operations and to establish standardized procedures for genome sequencing prior to acceptance of the first UDN patient Meanwhile, six gene function research R21 awards for the UDN were made in August and September As you can see from this table these six studies will investigate the underlying genetics biochemistry and or pathophysiology of newly diagnosed diseases in association with gene variants identified through the UDN in many cases using model systems Additionally, JAMA published two papers in November by investigators from the Baylor College of Medicine Sequencing Corps and the UCLA clinical site describing their experience in using clinical exome sequencing as a diagnostic tool Moving away from common fund but still remaining within trans-NIH initiatives The trans-NIH big data to knowledge or BD2K initiative aims to enable scientists to use big data to advance biomedical research The first round of awards was made shortly after the last council meeting This included 12 Centers of Excellence and the Data Discovery Index Coordination Consortium with the associated principal investigators gathering at a kickoff meeting in Bethesda in November At this meeting it was emphasized that they were expected to function as a consortium Similarly, the first set of BD2K training awards went out at the end of last fiscal year and these were for short courses open educational resources and mentored career development The associated principal investigators for the open educational resources also attended that November meeting There are a number of recently reviewed BD2K elements that will be funded in the upcoming months One is for software development and for targeted areas of need data wrangling, compression, visualization, and provenance The BD2K multi-counsel working group has reviewed these applications and a new version of the RFA with different targeted areas will be released later this year In addition, the training program has completed the review of applications for institutional pre-doctoral training programs in biomedical big data science and this RFA has a second receipt date in March In terms of future BD2K efforts and priorities The Commons is one of the biggest The goal is to have a space where data software and completed analyses are co-located in a cloud environment Small pilot projects some of which will be driven by the needs of specific NIH institutes and centers will be started in the coming months The NIH standards information resource will be a resource where existing data standards and associated metadata are gathered together allowing researchers to choose the best existing standard for a data set Another BD2K group is focused on sustainability of large biological resources This group is actually going to be hosting a workshop later this year to gather experts both within and outside of biomedicine to come up with possible solutions to the growing problem of sustaining biomedical data resources The BD2K training group has released an RFA for a Biomedical Data Science Training Coordination Center which will aim to develop a network of educators, mentors, and trainees and to produce an index for publicly available training materials Applications for this are due in March And finally, BD2K is also focused on creating a diverse Biomedical Data Science Workforce An RFA was posted in January to support creative educational activities that increase diversity focusing on research experiences and curriculum development Another thing related to the Common Fund IDASH is actually a common fund center funded as part of the National Centers for Biomedical Computing Program and is dedicated to developing innovative solutions to sharing data for analysis in healthcare and genomics while maintaining privacy Well, NHGRI funded an IDASH collaborating grant to Indiana University to address issues around privacy with genomic data in particular And using this funding this IDASH collaboration will hold the second IDASH privacy challenge in March A workshop to examine security issues related to genome analysis The two challenge topics for this workshop will be homomorphic encryption and the secure multi-party computing for secure genomic data analysis across institutions So that wraps up Common Fund Trans NIH Moving on then to our division of policy communication and education Starting with the Inter-Society Coordinating Committee for Practitioner Education and Genomics called the ISCC which has continued its work on improving the genomic literacy of healthcare practitioners and enhancing the practice of genomic medicine Now in August, Terry Minoglio and Michael Murray published a paper in Genetics and Medicine about the growing role of professional societies in educating clinicians in genomics At present, the group's membership includes individuals from professional societies representing physicians, dentists, pharmacists, nurses, and genetic counselors This past November, the group held its third in-person meeting where members discussed the group's progress to date developed plans for engaging CME representatives from the 51 professional societies and new federal partners and created new working groups to address physician-patient communications related to genomics and innovative approaches to the development of educational programs modeled after the successful program for training pathology residents in genomics Now NHGRI's new Genomic Health Care Branch Chief, Bob Wilden, is going to take over for Terry Minoglio as the NHGRI co-chair of the ISCC and the group's leaders will continue to explore ways to sustain the ISCC as its scope grows beyond NHGRI's reach And finally, you'll hear more about the ISCC in a talk by Terry Minoglio later in the open session Now, the Genetics and Genomics Competencies Center or G2C2 website is a free clearing house for healthcare provider-oriented educational resources It's managed by an editorial board and contains competencies for clinical providers from nursing, genetic counseling, physician assistants, and pharmacists disciplines And I'm now pleased to announce that with the help of a working group of the ISCC, which I just told you about, the site is now has physician competencies and peer-reviewed resources This ISCC working group continues to add resources to this, including journal articles, videos, and teaching method information And the site has recently been redesigned so that the searchable educational resources for physicians are linked to discipline-specific competency guidelines developed and published by the ISCC Providers can now target their educational efforts for competencies that they are lacking Also of interest to members of this council, on December 18th, President Obama signed into the law the Newborn Screening Saves Lives Reauthorization Act of 2014 which extends programs supporting newborn screening activities through fiscal year 2019 and reauthorizes the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children This reauthorization also directs the Department of Health and Human Services to update the common rule within two years and importantly requires that until the common rule is updated parental consent is required for the use of newborn blood spot samples in research This new consent requirement applies to the research use of blood spots collected after March 18th of this year Also of relevance, over the past year, NIH has rolled out a series of policy changes to enhance stewardship of clinical trial investments First, in October of 2014, NIH issued a new definition of clinical trial which went into effect on January 25th Under the new definition of clinical trials is a human-subject study that is prospective, interventional, and measures health-related outcomes The definition is significant because it dictates which studies are subject to specific reporting and monitoring requirements Second, on November 19th, NIH proposed changes to reporting policies The proposed changes are intended to improve transparency and maximize the utility of research investments by expecting that summary data from NIH-funded clinical trials is reported in clinicaltrials.gov within 12 months of the study's completion Previously, some smaller trials and some trials that were not FDA-regulated did not have reporting requirements We anticipate that clear requirements will improve the utility of genomics research data However, implementation of the policy will require input from the community and NIH is accepting public comments through February 19th Finally, on December 3rd, NIH proposed a new policy promoting a single IRB of record for multi-site studies Having one IRB for a multi-site study is aimed at streamlining review processes and expediting study launch The public comment period for this proposal closed January 29th Well, the five months since our last council meeting has seen quite a bit of action with regard to FDA's decision to exercise oversight over laboratory-developed tests or LDTs Currently, if a molecular diagnostic test is developed and only performed in a single laboratory, it is classified as an LDT and receives no FDA oversight In contrast, a similar diagnostic test that is marketed as a kit and sold to multiple labs has been subject to FDA oversight for many years As reported to council at the September meeting, the FDA recently laid out in draft guidance those aims that basically hoped to level the playing field So during the 120-day public comment period on the draft guidance, FDA held a two-day workshop to hear public testimony and stimulate discussion Several NHGRI staff members acted as moderators for panel discussions and over the course of those two days the agency heard a wide range of views and opinions from stakeholders The debate over the appropriate level of FDA regulation for diagnostics is also being conducted in the literature including a pair of commentaries in JAMA at the beginning of January A one by Joshua Sharfstein argues in favor of FDA regulating LDTs while a second written by Council's own Jim Evans and ACMG's Mike Watson argues against such a move Although the public comment period for FDA's LDT guidance is now closed, the community has another opportunity to advise the agency on how best to regulate the use of next-generation DNA sequencing and diagnostic testing Last year, FDA published a white paper on the challenges of regulating next-generation DNA sequencing assays compared to more traditional in vitro diagnostics that have more clearly defined intended uses And FDA is now holding a public workshop at NIH on February 20th specifically to explore this topic NHGRI has for many years maintained an online resource for issues pertaining to informed consent processes for genomics research An update to this informed consent resource went live on genome.gov just last week The website is designed to help researchers and IRBs consider informed consent issues that are specific to the context of genomic science It includes discussion of topics essential to genomics research such as consideration of families, studies involving children and broad versus specific consent It also includes sample language and consent forms as well as a discussion of relevant regulations and policies Now some of the new and updated content relates to data repositories and biobanking whole genome and whole exome sequencing data sharing and return of results And thanks to many reviewers including some council members who provided feedback during the development of this updated resource We hope that this is a valuable resource to the community and we're actively interested in getting comments or suggestions In fact there's a dedicated area for information exchange and sharing of useful consent language and we give particularly here an email address that you can use Well as the Genome Unlocking Lives Code exhibition ended its tenure at the National Museum of Natural History and began its North American tour A closing symposium was held in September to explore the importance of genomic advances and what the next decade holds for genomics and genomic medicine More than 300 people filled the Barrett Auditorium at the museum to hear a series of panels One included me and Anne Wojcicki of 23andMe and Rick Lifton from Yao Another one featured Partis Sebedi from Broad and Harvard and Charles Rotimi from NHGRI and Seema Kumar from Johnson & Johnson Panelists discussed the future of human genomics where research is headed the role of a private citizen in genomic testing and research and genomics and global health Then in the evening we convened another panel for the public and they were treated to a conversation featuring Washington Post and Vice-Columbus Carolyn Hacks and Barbara Bisaker from NHGRI and also Dave Vali from Johns Hopkins and the panelists answered audience questions about health issues, genetics dealing with diseases and their personal life Well realizing that Genome Unlocking Lives Code traveling exhibition would make its first stop in San Diego at the Rubinage Fleet Center NHGRI was presented with a wonderful opportunity to highlight the exhibition and to work with some of the local organizations that provide on-the-ground support to military families in the San Diego area So in November NHGRI partnered with the San Diego Military Family Collaborative to host a Military Family Day at the Fleet Center More than 700 people from the military families ranging from infants in arms to retired military attended the event Military families were able to visit the Fleet Science Center at no charge participate in genomics-focused hands-on activities with scientists from local universities and organizations and also of course to see the actual exhibition and get a complimentary launch and receive information from more than 30 San Diego area resource providers But the exhibition had an uproot from San Diego to keep moving And so the Genome Unlocking Lives Code exhibition is now in the middle of its busy travel schedule around North America The first stop was San Diego But that concluded on January 2nd during which time more than 50,000 people visited the exhibition over those three months But it now travels and has traveled up to the Tech Museum of Innovation in San Jose where it will reside until the end of April After San Jose it's on to my hometown St. Louis until mid-September and then on to Portland, Oregon until the very beginning of next year And then the first destination for 2016 which Howard Jacobs is just waiting for will be Milwaukee where it will be from January until the end of April of next year And each of these destinations I can tell you NHGRA is working in partnership with science centers, universities, communities and also our grantees to develop programs for targeted populations as well as reaching out to the local health professionals And as always, just check the exhibition's website at unlockinglifescode.org for the most up-to-date information on where the exhibition is traveling and any programming associated with it Finally, getting to the home stretch here Intramural research program in NHGRI But before I talk about our specific intramural program I should actually tell you that in the middle of last year Francis Collins established yet another working group of his advisory committee to the director This one focused on long-term strategic planning for the broader NIH intramural research program The working group was charged with identifying new areas of opportunity for the intramural research program Approaches to capitalize on its uniqueness and ways to ensure its healthy and productive future I can tell you that council member Bob Nussbaum actually served on this working group In December, the working group delivered its report which contains recommendations for a number of structural and strategic changes including the creation of a trans-NIH intramural innovation fund and modifications to the existing routines for external review of the intramural investigators And the NIH leadership including institute directors and scientific directors are now working to decide which of the recommended elements will be implemented and how to implement them In terms of some accolades for some of our own intramural investigators Julie Segre, senior investigator and chief of the NHGRI Translational and Functional Genomics Branch was selected for the 2014 Chanel series research award She received this honor and recognition of her research on the microbiome of human skin Bill Gaul, our institute's clinical director and director of the NIH undiagnosed diseases program received the 2014 Rare Voice Award in the government agency category This award recognizes organizations and individuals who go above and beyond to become political to become policy leaders and political advocates in their state and nation Barr Beesicker, associate investigator in the NHGRI social behavioral research branch received the Natalie Weisberger Paul National Achievement Award This annual award is most is given to the most distinguished award given by the National Society of Genetic Counselors and honors an outstanding individual whose exemplary national achievements and volunteer activities have served the society and the profession And Charles Rattimi Chief of the NHGRI Metabolic Cardiovascular and Inflammatory Disease Genomics Branch and director of the NIH Center for Research on Genomics and Global Health received the 2014 South African Medical Research Counsel Scientific Merit Award for a seminal scientific contribution The award reflecting his long-standing record of an important role he has played in performing genetics and genomics research And finally, Sherjoe Sen formerly a post-doctoral research fellow who was until recently tri-mentored by Les Beesicker and Jim Mulligan and actually me received the 2014 CW Cotterman Award from the American Society for Human Genetics Sherjoe's paper entitled Integrative DNA, RNA and Protein Evidence connects Tremel IV to coronary artery calcification was published in the July 2014 issue of the American Journal of Human Genetics and this paper was selected as one of two publications within the previous year that represented outstanding contributions to the field of genetics earning Sherjoe a 2014 CW Cotterman Award Other highlights within the intramural program since the last council meeting Charles Rattimi and colleagues involved in the African Genome Variation Project published the first comprehensive characterization of genomic diversity across sub-Saharan Africa the paper was published in Nature Julie Segre and her NCI collaborators published their genomic study of the metagenome of 18 skin sites revealing the unique microbiota of each that research was also published in Nature and then Chuck Venditti and colleagues published results of their study of adeno-associated viral vectors for gene therapy and mouse models and methamelonic acid- methamelonic acidemia describing important factors in gene delivery that are critical in the subsequent development of hepatic cancer and this paper was published in the Journal of Clinical Investigation Before ending my director's report I just want to put in a plug and say anyone wishing to receive my monthly email update the genomics landscape simply go to this listserv and information provided and you can certainly enroll our numbers grow every month and finally a personal thanks to everyone who helped put this very busy director's report very busy time for the past four months put it all together and pull in all the slides and information to convey all this to council and others watching in particular thanks as always to Chris Wetterstrand who's the ringleader of all of this and makes the final PowerPoint slides come together but also our communications group who are helping make this widely available on the web That was a long director's report but before I end I just want to do two more brief things just to show you how crazy things have been I want to share one funny story and then tell you one serious thing the funny story is that you could tell it has been a crazy four months or something since and especially in the roll up or the all the events leading out to the announcement of the president's precision medicine initiative many of us were doing just heroic things with all the documents going back and forth and all the planning going back and forth so we had enough on our plate already and then the president's announcement was on the Friday and about Tuesday evening it started to be Laura Rodriguez and I in particular started to get emails from the White House in particular the reason we and this reflects sort of the day in the life of the NHR in fact I may add this as a new slide in my director's report because there always seems to be something happening every four months that's insane this would be the insane category as if there wasn't enough going on Laura and I were both exquisitely busy when we start getting emailed from the White House because people there especially the Office of Science, Technology and Policy were knew that immediately outside my office is this nice model of a double helix and this is the view from my desk so if we zoom in a little this is my immediately outside my office and they knew it was there and they wanted it for the announcement and they said get it to us and we need it like and the next morning we were told that like five in the morning we need it today because they probably want to clear it and they want to make sure they have everything ready two days in advance and so this is an icon of the if I can see very two pictures you saw on the right where the photographers love take pictures of staff with this thing so I've had it for 20 years and it's been used many many times and maybe that's part of the reason why the White House wanted this as sort of an icon next to the president and so this thing's a little fragile but we have somehow get it to the White House so we don't have enough to do here we are boxing the darn thing up you know in a very kluji way my assistant in net was tasked with this at 6th right oh no I'm getting there 6th this is 6 30 in the morning or maybe 7 30 in the morning here we are coming up with a kluji way to brace it so that a courier could take it down to the White House we had to like cap it off and get it all set and you know tape it up he's a lot of tape yeah a lot of tape it did take some extra effort to get it through the secret service but they were motivated and there it was that's the picture for me waiting for the president and waiting for the president to come out and eventually he did come out and he just loved it in fact he pointed out how the DNA genomics just rocks and so so the double helix is now famous because it's got to be next to Obama now I will tell you because some of you probably do am I going to get it back and am I going to get it back as a model or a box of G's, A's, T's and C's that's what I was worried about but they actually took great care of it and this is a picture I took of it Saturday afternoon it is back where it belongs and it's I don't have to worry about it anymore so that was my humorous story my more serious story which actually is really directed to the council so I had an odometer moment as I called it December 1 of just you know two months ago or something like that was my fifth year as some people are shocked by in some ways I'm sort of shocked by and a lot has happened obviously in five years actually I was reminiscing the fact that we've lost several council members from being here in person because of the snow my first council which was exactly five years ago now happened obviously I started December 1st first council meeting was in February and I got all ready for it and it was very fast and it was all very new for me and then we got hit with a snowmageddon and we ended up no council members came to it because there's no way you can get in town and we took it all by phone we converted it all by phone so I'm very sympathetic to these crazy things that happen we have February council meetings but such we have to do with it but it's been great I feel like things have gone extremely well I've made many thanks to members of the institute at that magic five-year odometer moment but I actually wanted to make sure to thank council because it was also I think very relevant to point out that I think we've done a lot to enhance how we use our council and enhance the relation of the council over the five years I've been director and I think it's working I rely on you as does all the staff constantly extensively and I will tell you that it really came into focus and thinking about this last week when last week happened to be the week I invite I make the phone calls to invite the new slate the new members which we'll eventually be hearing about we will nominate these individuals now for new members and I have phone conversations as I have with each of you and really just stressed what an incredibly good relationship it is between council members and the institute in particular me and so I just want to really personally thank all of you for your valued input over my and some of you have seen me over the four out of those five years especially those who are getting near the end at least three of the five years those getting near the end of your tenure on council but just my own personal thanks to all of you I think this is a terrific group to interact with we take your meetings very seriously we take your advice very seriously and I really regard it as one of the special parts of the job so I know that was a lengthy director's part I knew it was going to be but thank you for your attention happy to take any questions and Rudy's not going to let too many questions I'm sure we're going to be on a clock now so but Bob one quick comment congratulations on transfecting the White House yeah and I just wanted to ask you a question about the cohort issue I didn't hear any mention of the million veterans project and sort of what the relationship is there so without question all available cohorts including the million veterans is going to be part of the conversation and certainly they're going to be prominently they're definitely present at this the workshop and remind me if anybody like Terry remembers are they giving a presentation at the workshop or there you go absolutely part of the discussion and nothing again like a lot of things to all to be determined exactly how all this works but no question they've been part of the conversation from the beginning if you need partial liaison I'm on their advisory and we did I did know that and this has come up and that's good to know yeah Tony I just wanted to know whether there's been thought put into collaborating or learning from the UK Biobank which has a half a million I think they started in 2006 and I we absolutely know that and I know Rory is coming you know come here right here Rory's coming to the workshop yeah he's actually a critical part of our working group and I'm actually on their advisory board as well so we're using their lessons there's no question maximizing these cross-fertilization is going to be critical this never was the idea do this in isolation build it from scratch all this is to broker offers off of existing expertise and cohorts yes Dan this is sort of like a bureaucratic question but who's going to run this thing what Institute is going to where is it where's it going to live all to be determined at least I think it's being right now shaped in a trans NIH way by and all aspects of it are going to be to broker the expertise of what currently exists in many Institutes with time when it's taken more shape and we understand what's going to be needed of those sorts of governance issues I think will be fleshed out in greater detail yes Carlos Eric is the so first I want to mention what I mentioned on the other call that we were on about making sure that the cohort is diverse and representative and properly powered which is a big issue right you know that one of the big hurdles in multi and trans ethnic mapping is that you know when you look at the minority groups they often tend to have smaller sample sizes and so you can't do primary discovery in those groups and it's really important that that be part of the design and I know that's on the forefront of what you're thinking about the other is you know as you're building the cohort is there a plan to do say genotyping of all million people in year one because that could be a pretty amazing resource before you start doing the sequencing or is it all going to be you know sequence in year five after you've built the cohort or is that all sort of up in the air I would say this is all up in the air I mean it's exactly what starting Wednesday will be discussed there is there is nothing etched in anything other than very light pencil which was mostly related to get get a bunch of people together for an initial workshop as quick as possible because strategically right you may want to pick off all the relatively common variants first by genotyping and you know you're going to want that date date anyway for quality control so so thinking about a staggered model might make might be something those going to the meeting might want to continue okay Rudy I'll turn this over to you yeah so please be back from lunch at 12 45 then we'll start with Terry's presentation on the genomic medicine working group so 12 45 back here please