 Well, good morning everyone. Let me remind you that the open session of this council meeting is being webcast live As we now webcast all of our council meetings the open session and in addition we are creating a permanent video archive of these open sessions and Making them available on the web sort of as permanent historic Material and that includes both the video presentations as well as the various Documents that are associated with it including the presentations themselves and in particular for new council members and I point this out Especially to Amy and Jim who are seeing this for the first time And but also for any web viewers who are watching our council proceedings for the first time I want you to make you aware of this electronic resource that we now have associated with my director's report Sort of analogous to a supplemental materials made available with a published paper And it could be accessed at this convenient URL listed at the bottom of the slide And so the slides that I'm showing during my director's report are also made available at this site either as a PDF file Or as the actual native PowerPoint file and for slides that are associated with specific documents or relevant websites There's a document number shown on the bottom right of the slide And that indicates where where the reference materials for that slide can be accessed from this table as shown on the slide here and In addition to the video archive, I just mentioned All the web link all these link documents We will all this would be available for you to use or to point people to Forever as far as we're concerned because we're going to be archiving us. Okay, so that's the that's the logistics associated with my director report Let me remind you what we are doing during the open session They're going to be multiple other presentations during the open session and my director's report is tailored around these presentations So that I'll actually won't discuss the much detail areas that are going to be discussed in greater detail by others Jeff Schloss is going to give an update on DNA sequencing technologies circa 2012 Karen Rothenberg who is a Special advisor to me on sabbatical this year from University of Maryland law school will give a talk on Genomics Society the LC research program and beyond and then as I mentioned earlier Mark I was slated to give a portfolio review that will now be deferred until the May council meeting We also have a series of concept clearances in addition to the talks You'll be hearing concept clearances on the page renewal on clinical exploratory sequencing coordinating center And genomic medicine pilot projects in addition a concept clearance on clean action on Centers of excellence and LC research and also high throughput genomic analyses and children with newborn screening disorders This will likely not be the order. It's what this is the list that's on the agenda We will likely change the order for for various reasons, but we will come obvious when we get to those Finally, there's actually been multiple NHGRI sponsored meetings held since the last council meeting For example a meeting on genomic literacy will be summarized in a presentation by Vince Bonham And I'll actually be referring to some other meetings later in my director's report and then yours yet additional meetings That I won't say anything about because or very little about because they'll be discussed within the context of the concept clearances So for the rest of my director's report I will be covering these seven areas which the seven areas I talk about each time and I think there's a great framework For getting through all the things we want to update you about since our last council meeting starting with general NHGRI updates I Would start off by telling you that the most substantive overarching thing to report about NHGRI is that we've moved forward in Proposing changes to our organizational structure and shown here is a website describing the details about both our proposed changes As well as the process we're following in proposing this reorganization The ladder involves holding public meetings to provide a forum for feedback about our proposed changes And the second of two such public meetings will be held at 1 p.m Today as part of the open session of this council meeting and so for that reason I'm not going to discuss our proposed reorganization at this time I'll defer it until my presentation at 1 o'clock at this past falls International Congress of Human Genetics American Society of Human Genetics Joint Meeting NHGRI organized two very successful sessions One was an invited session on emerging ethical issues in large-scale international genomics research Collaborations that was moderated by NHGRI staff member Gene McEwen and former council member Polaro Zario Speakers came from various parts of the world to discuss both general issues and their unique perspectives These issues are arising more and more frequently especially for community resource projects that involve plans for broad data release and in situations Where different cultural values and norms as well as different legal and regulatory requirements have to be reconciled the second session And that NHGRI was involved in organizing was a tutorial And using 1,000 genomes project data this gathering was attended by over 300 people and importantly We there we were there videotaping that session and that has now that videotape has now been downloaded over 350 times from our website in the URL that you can access a document to Among the many publications emanating from NHGRI since the last council meeting was an invited commentary published in Cell In which Terry Minolio and myself co-authored a piece that describes some of the clinical implications of genomic advances I bring this to your attention because Cell specifically asked us to write Something about the near-term clinical applications of genomics that provided a bit more detail than what we had described in our strategic plan published last February in in nature and this is the piece that came about from that invitation and On the lighter side but important and those who think that NHGRI staff members are only good at genomics I will point out to you that long time NHGRI or Betty Graham also has a long and distinguished career as a competitive Fencer in fact Betty traveled to Croatia in October as a member of the USA veteran fencing team to compete in the 2011 World Veterans Fencing Championship and lo and behold Betty came home with the bronze medal in her class and if my There is more if my sources are correct Betty is the current US veteran national champion in both foil and epi and The 2011 veteran rule championships was the ninth world championships at which she has represented the United States So it is so my first thing is congratulations Zorro I mean congratulations Betty and And all appeals for grants now will go directly to Betty with a sword in her hand Okay, that's why I want to tell you about NHGRI Now moving on to general NIH updates Species speaking of swashbuckling The most significant organizational news at NIH in recent months was the creation of a new NIH center the National Center for Advancing Translational Sciences or NCATS now as part of the fiscal year 2012 Omnibus appropriations bill the National Center for Research Resources or NCRR was dissolved and NCATS was established and NCATS now has a budget this fiscal year of $575 million Additional details the acting director of NCATS is Tom Insel the director of NIMH mental health Institute and the acting deputy Director of NCATS is Kathy Hudson who is the NIH deputy director for science outreach and policy Note that the search for a permanent NCATS director is very active I can tell you it's very active because I Along with Tom Insel are the co-chairs of that search committee and we are at a very advanced stage at identifying candidates and and helping Francis Collins identify the founding Director for this new center now There are many components that are now housed within NCATS particularly notable ones include the clinical and translational science awards the CTSA program The Cures acceleration network the newly created division of preclinical innovation. That's headed by Chris Austin now I point out that the ladder has mostly been formed from the National Center for translational Therapeutics or NCTT and entity that grew up and operated with NHGRI for almost a decade And so with the creation of NCATS about a hundred or actually more than a hundred NHGRI employees all under Chris Austin's leadership Departed our Institute in block as part of the creation of NCATS And so this has had an important impact on our Institute as well But it's very exciting to see this new center finally formed and now getting operational Now in addition to the NCR our programs that went to NCATS other components were assigned to other NIH Either to the NIH office of the director or to one of five different institutes and I list them there And there's a fairly lengthy list of such NCR elements and where they got relocated And if you're interested in seeing that that's available on a website that is linked to document number five As I have mentioned previously and in very much the Continued area related to reorganization the NIH scientific management or review board SMRB Has recommended the merger of two NIH institutes involved in research related to addiction and substance use specifically the National Institute on drug abuse or NIDA and The National Institute on alcohol abuse and alcoholism known as NIAAA as we've come to learn Abolishing or emerging or creating or even reorganizing NIH institutes or centers is a long and complex process And so indeed last week NIH issued a request for information known as an RFI Seeking input into the scientific strategic plan for the proposed new merged Institute Which has preliminarily been named the National Institute of Substance Use and Addiction Disorders So if you have anything you want to provide about that that input is due at the site and document 6 by May 11th Which is why I wanted to bring it to your attention now Also at the NIH level there was a joint NIH industry workshop on the subject of target validation this past November Now this gathering included high-level representatives for virtually all of the major pharmaceutical companies with the goal of exploring how to use Use various scientific opportunities I will tell you with a particular emphasis on genomic advances to improve the process of identifying suitable targets for drug development The executive summary of that workshop is available as document 7 Well, not surprisingly NHGRI has been asked to help with many of these areas Especially in the future. So for example, I am now serving on an overarching steering committee with Pharmaceutical representatives and other NIH representatives for all of the efforts that are being packaged under the under the general area of target validation Terry Monoglio of NHGRI will be co-leading an NIH industry academia working group to explore possible genomics oriented projects That would move from genotype to phenotype or from phenotype to genotype in pursuit of identifying validating such targets And I'll also tell you that NHGRI has been asked to organize two workshops that will be relevant to these efforts One on the notion of aggregating genome sequence data in a fashion to accelerate genomic discoveries And one on exploring the merits of using different types of cohorts in genome sequencing projects Obviously both of these workshops are very relevant to things we're interested in But they'll also feed into the kinds of deliberations going on around some of the strategic planning in target validation And so it will serve both purposes Well moving on another critical area of NIH news relates to the budget situation So for this we try to find humor where we can although there isn't very much funny about the current situation But let me tell you where we are Recall that when we last met Congress was still debating the funding levels for federal agencies for fiscal year 2012 and that NHGRI's budget for the current fiscal year was Unclear as you no doubt now know Congress was able to complete this Budgeting process just before the holidays with the passage of a megabus bill containing funding for most of the federal government This means that we now know NHGRI's budget until the end of September of this year Specifically recall that the president had requested an increase of NHGRI's budget to 200 to 525 million In fiscal 2012 up from 511 million in fiscal year 2011 This was the figure in a bill introduced in the house While a Senate bill passed by the Appropriations Committee had NHGRI getting a five million dollar decrease in our budget Well when all the dust settled we ended up somewhere in between a very slight increase over fiscal year 2011 a total of 513 million dollars or an increase of just under 0.3 percent So we essentially end up being flat with respect to last year a sadly Flat becomes the new feel-good budget Recalibrating your expectations such that you're happy to have dodged the bullet of a serious budget cut But the next uncertainty Is the fiscal year 2013 budget which will be proposed and debated with the backdrop of an election year This is further complicated by the recent failure to reach a deal for deficit reduction So recall the creation of the super committee As part of the budget control act a law that was passed last year to limit government spending over the next decade And the charge to the super committee was by November 23rd the past November 23rd To identify ways to reduce the deficit by at least 1.2 trillion dollars over the next decade Well the super committee was not successful Now failure of the super committee triggers an automatic across the board 1.2 trillion dollar cut to federal agencies in 2013 and in theory this would amount to an eight to nine percent Reduction to NHGRI's budget starting next January 2nd, but actually retroactive to October 1 of this year both both actually you all federal all All non-military actually maybe this across the board, but it's absolutely NIH Well while seemingly unthinkable We could not ignore Developing what if scenarios to deal with such a circumstance But the overall fiscal year third 2013 budgeting process must still march forward So today is actually a significant day in that the president will actually deliver His fiscal year 2013 budget to Congress which will include the proposed funding level for NIH and NHGRI In fact stories have already come out over the weekend In anticipation of what the president is going to announce today in releasing his budget So that's actually all I can say about the president's fiscal year 13 budget for now But later today I can say more and I will once the president has formally made his announcement I'll be able to tell you what this that the president's budget is for 2013, but recognize This is all taking place in the context of an election year under concerns about The automatic sequestration eight to nine percent It is a very complicated circumstance that we are going to be living in over the next year or so or at least 11 months Other news at the NIH level in January of 2011 President Obama signed the National Alzheimer's Project Act Which calls for an aggressive and coordinated national Alzheimer's disease plan as Part of that plan DHHS Secretary Sebelius announced last week That NIH would make available 50 million dollars for Alzheimer's research in fiscal year 2012 and then 80 million dollars in fiscal year 2013 This is additional money beyond what's already being spent on Alzheimer's Now these efforts will include genomic studies aiming to identify genes that increase risk for the disease And it is very likely that NHGRI will be involved in this research The details about how NHGRI will become involved are actively being worked out And we will undoubtedly have more to report about this at the May council meeting Moving on to honors a huge honor was bestowed upon NIH's past fall when the NIH clinical center was awarded the 2011 Lasker Bloomberg Public Service Award Largely regarded as the crown jewel of the NIH intramural research program The NIH clinical center was given this highly prestigious award for serving as a model institution as transform scientific advances Into innovative therapies and has provided high quality care to numerous patients In November a secretary of state Hillary Rodden Clinton Visited NIH to deliver a major policy speech in which he called for a renewed push for an AIDS-free generation The speech marked the 30th year in the fight against HIV AIDS and kicked off preparation for world AIDS day Activities and the international conference AIDS 2012 which will be held in Washington DC next June also at the NIH level Recognizing the pervasive bottleneck and challenges related to big data and informatics an area obvious of particular interest to NHGRI of interest to this council and certainly of interest to the genomics community Francis Collins established a new working group of his advisory committee to the director This working group aims to investigate the management integration analysis of large biomedical data sets And it's called the NIH data and informatics working group And then the group is co-chaired by David Dometz of the University of Wisconsin and Larry Tadeback NIH deputy director and includes members such as Russ Altman, David Botstein, Don Masis, and actually includes council member Jill Miseroff Now recommendations from this working group are due this summer And meanwhile NHGRI and NIGMS have been asked to co-lead a trans NIH working group an internal working group To take the recommendations forward in the area of molecular data specifically genomics data predominantly And other NIH working groups will deal with other areas such as phenotype data and imaging data. They're also being considered So this advisory this working group of the advisory committee the director will wind down by the summer And then there'll be an internal group that will pick up and move forward from those recommendations beyond that And our institute and GMS will be Co-leading that internal group now as part of their deliberations the NIH data and informatics working group has issued a request for information Another one of these RFIs to solicit input from the community on a broad series of topics relevant to this complex area A subset of those topics is listed here And while and there's additional detailed subtopics that can be found in the RFI itself A link of which is available on document 12 And I bring this to your attention because the RFI will accept public comments through March 12th of 2012 March 12th is an easy day for me to remember It's when my son is going to turn 16 and my life will never be the same But that's besides the point But please share this link with your colleagues and any organizations that you feel are appropriate Because resulting information is obviously of great interest to us At NHGRI and I really do think that having this working group get as much information as they can All that information will be passed off to this new working group that we will be involved in I think it'll be very important for us to have as much data and information in front of us as possible Okay, so Let me move on from the NIH and now talk about genomics In particular and updates that have happened since last council meeting Let's start with a sad news That the legendary geneticist James Crow died January 4th 2012 He was 95 years old and was still actively working at the University of Wisconsin at the beginning of this academic year A James Crow was a leader in the field of population genetics who helped shape public policy about Atomic radiation damage as well as the use of DNA in the courtroom He was also a highly regarded genetics teacher His crow's notes as they were called was a textbook widely used at the college level for introduction to genetics courses I know crow's notes extremely well because I took jim james crow's Genetics 101 course in 1979 I will tell you maybe I shouldn't admit this. It was by far the most substantive genetics course work I've taken in my entire life. It was it was incredible. It was awesome It was one of these things where especially University of Wisconsin, you know Six five six hundred students would be in attendance I would usually sit up in the balcony because you couldn't even get a seat on the main and the main area And um and everybody would come to watch and he just sat there with chalk And which is sit there and and just have the group completely enamored. He was a fabulous teacher So truly tragic loss, but boy does he leave a legacy of many people? He has trained and many people. He has talked and a major impact on the field Last week we learned that genetics pioneer Norton zender died on february 3rd. He was 83 years old Dr. Zender was involved in some of the earliest planning for the human genome project And in fact served as a member of this advisory council When we were then known as the national center for human genome research Among as many scientific accomplishments was the discovery of transduction in bacteria He was the john d. Rockefeller junior professor emeritus at the Rockefeller university where he spent his entire research career Moving on to awards David all shuler of the brode institute and harvard university and certainly well known to everyone In this room was given the 2011 curt stern award by the american site of human genetics David was honored for his outstanding contributions as a leader in the study of human genetic variation And its application to common complex diseases using tools and knowledge gained from the human genome project And the curt stern award is given annually by the american site of human genetics and recognition of major scientific achievement In human genetics that has occurred in the last 10 years Andy feinberg of john hopkins, johns hopkins university and nhri grantee was given an nyh director's pioneer award This award was based on a proposal. He submitted entitled a general stochastic epigenetic model for evolution development and disease Congratulations to andy Fioru fox was a participant in the nhri diversity action plan program He also spent a couple of years in the nhri intramural research program And he is now in f 30 is now on an f 31 fellowship at the university of washington And he was a recently awarded the best graduate student presenter for genetics at the society for the advancement of chicanos and native americans in science national conference So congratulations to him Manolis kellis an associate professor in the department of electrical engineering computer science at mit Was awarded the 2011 niki award by the athens information technology center of excellence for research and education The award which is presented annually honors prominent greeks or individuals of greek descent Who are internationally recognized for their contributions to science and technology and who inspire a generation of scientists Another individual well known to nhri herald chipiro will receive the public welfare medal the national academy of sciences most prestigious award The medal was presented annually to honor someone demonstrating extraordinary use of science for the public good Throughout his career herald has helped shape of science and public policy And the public welfare medal will be presented to herald on april 30th during the academy's 149th annual meeting and to put in perspective previous recipients of the medal include neil lane maxine singer c everd coop and carl sagan Shown here are the newly elected leaders of the american society of human genetics All are good friends colleagues and grantees or advisors of nhri includes jeff murray as president elect jeff duic as treasurer And then vivian chung evan eichler and richard gibbs on the board of directors And then Similarly a number of individuals with ties to nhri were recently elected to the institute of medicine marty blazer vivian chung again claire frazier ligott richard gibbs and david roman congratulations to all of them And at the same hole the same holds true for recently elected fellows of triple as andy feinberg ed marquardt and dick macombie and rick meyers right sitting right here on council so congratulations to all of you Moving on to sort of the policy arena last fall congress passed the lehi smith america invents act reforming us patent law To align it with the systems used by other countries of interest Buried within this act as a requirement for the us patent and trademark office to conduct a study on genetic testing Specifically the law requires that the pto prepare a report for congress On quote effective ways to provide independent confirming genetic diagnostic test activity Where gene patents and exclusive licensing for primary genetic diagnostic tests exists and a quote The study is designed to examine the concern that gene patents and exclusive licenses can prevent patient access to genetic testing The report is due to congress by june 16th this year and the pto is holding public meetings in february and in march The public has further invited to submit written comments to the agency by march 26th And i will plan to report back on their findings at a future council meeting On february 2nd of this year the presidential commission for the study of bioethical issues met in san francisco to discuss Bioethical issues associated with whole genome sequencing The commission heard from a number of experts including former nhri council members richard gibbs and palaro sario The commission's focus was mainly on issues of privacy Although the discussions frequently returned to the issue of consent and how to make it meaningfully informed In light of very low genomic literacy among clinicians and the general public The commission will be publishing a report on the subject later this year and nhri staffer in close contact with the commission staff Both to serve as a resource for any information they might need but also to provide input on possible directions The commission might pursue This past july the institute of medicine roundtable on translating genomic-based research for health Hosted a workshop to highlight and identify the challenges and opportunities in integrating large-scale genomic information into clinical practice The main objective of the workshop was to start a discussion on what needs to be done to prepare The necessary infrastructure and to address the various challenges for realizing genomic medicine The workshop summary is shown here and is available as document 22 We have heard that this report has generated the most interest of any of the meetings and reports generated to date by the roundtable There'll be a follow-up meeting in july of this year exploring aspects of the economics of clinical and research applications Of whole genome sequencing that nhri's greg fero will be cheering motivated by the explosion of molecular data on humans particularly data associated with individual patients And the sense that there are large as yet untapped opportunities to use these data to improve health outcomes The national academy's issued this report on towards precision medicine building a knowledge network for biomedical research and a new taxonomy of disease And the report Explores the feasibility of developing such a taxonomy and developing a potential framework for creating one So this report notes that moving towards individualized medicine requires all researchers and health care providers Have access to very large cells Sets of health related and disease related data linked to individual patients These data are also critical for developing the information commons the knowledge network of disease and ultimately the new taxonomy Another report as you may recall in may of last year the betel technology partnership practice published an economic analysis That was supported by life technologies But related to the economic and functional impacts of the federal investment in genomics rnd Through the human genome project and beyond well recently The betel group released a related report on behalf of the american clinical laboratory association that examines the economic and functional impacts of genetic and genomic clinical laboratory testing And the study found that even though it's in an early stage the genetics and genomics clinical Testing sector has been responsible for directly and indirectly employing 116,000 workers Generating nearly six billion dollars in personal income and providing 1.2 billion dollars annually in federal tax revenue Our good friends at the american college of medical genetics recently decided to change their name of their organization To the american college of medical genetics and genomics This will take place in march at their annual meeting. However, they will still maintain their same acronym acmg And according to acmg the name change recognizes the increasingly central role of medical genomics And it's important along importance alongside genetics and fulfilling the mission of the american college of medical genetics nhdri Continues to feature on our website a monthly feature highlighting a genomic advance of the month Recent topics have included a genomics approach to the study of trauma The sequence of the full genome of a back of the bacteria responsible for the black death Next generation sequencing targeted at known tumor suppressor genes And the use of previously collected GWAS data to uncover new genetic pathways that regulate how our bodies make platelets I will now move to my regular genomics in the news features Starting with the recently sequenced genomes that captured news attention For example, the genome of an Aboriginal man who lived in the 1920s was sequenced An analysis of the resulting sequence data suggests that his ancestors started their migratory journey More than 60,000 years ago branching off from humans who left Africa Scientists recently sequenced the genome of a dutch woman who lived to age 115 She was born in 1890 and passed away in 2004 This woman overcame breast cancer at the age of 100 and never showed signs of dementia or Alzheimer's disease In january, the scientist ran a feature story about Elaine Martis entitled high tech choir master. Congratulations Elaine Also in january the new york times ran a feature article about eric lander entitled power in numbers That article was accompanied by various pictures of eric including this one of him winning first place in the 1974 science talent search In the same year he made the american team in the mathematics olympiad And here is another picture from that same story that more accurately captures his modern look and energy filled gestures And you just you just don't want your neck to be Another new york times article highlighted the genomic data explosion And had an interesting picture of dick macombi and a sequencing flow cell. It's actually a good photo Rather interesting Encode was identified by nature magazine as a potential quote key finding an event that may emerge in 2012 An accompanying article foreshadows a major update from the project that is expected to be reported in a major publication in 2012 I do find it funny that nature news reports the future by knowing about a paper that might be under review in the same journal They really went on a limb on that one didn't they looking at my encode colleagues here So but still they gave good call out about what's going to happen in 2012 well deserved The nhgi sequencing technology development program was featured in the flurry of stories reported in the wall street journal Reuters national public radio nature and other news outlets These reports feature the announcement early last month that two major sequencing technology companies were released news systems in 2012 That are predicted to enable sequencing a whole human genome by a thousand dollars I'm sure this will play nicely into jeff schloss's talk later today But then we also have strange stories we always do Some of you may have followed this story that occurred last year Where there was an episa protest that was broken up with pepper spray by the uc davis police That caused all sorts of problems and in the aftermath of it It was a new story where the uc president talked about how free speech is part of the dna of this university Which I thought was interesting The thing I thought was pretty interesting that dna that universities have dna and that I'm not telling the truth here That very week I went like the day after the story came out I went and got new tires put on my car and I was I was sitting there in the waiting room There was a a sign up this was a sign took a picture of my blackberry What's in your car's dna our exclusive dna you know diagnostic needs assessment needs and a double helix coming out So what we now know is that universities have dna and cars have dna and with such developments It's clear that our institute's portfolio of dna research will only increase in the future Okay Those are my news stories. Let me move on to the extramural program Well following the extensive discussion with council about the renewal of our genome sequencing program at the september meeting We made final decisions and announced the new awards in december recall that there are four major components Of the renewed nhri genome sequencing program The first component is the large-scale genome sequencing centers Which was renewed for four years at a year one funding level of 86 million dollars And as you all know the funded centers are at baler college of medicine the brode institute in washington university With the pi's in year one funding levels shown on this slide The large-scale genome sequencing centers will conduct Research into how the human genome works as well as studies of the genetic contributions to complex illnesses and ongoing special projects such as the cancer genome atlas The centers will also be involved in new medical initiatives and will continue to implement technological advances in dna sequencing Develop new technologies and software to analyze and understand the massive amounts of dna sequence data now being produced and continue to train genomic researchers The second component of our renewed genome sequencing program involved the creation of new mendelian centers Mendelian disorders genome centers For this nhri partnered with the national heartland and blood institute to invest 48 million dollars over the next four years To fund three centers with nhri and nhlbi contributing 40 million and eight million dollars respectively The funded centers are located at the university of washington Which will also serve as the coordination center for the group at yale university And then a partnership between baler college of medicine and the johns hopkins university the pi's and funding levels are shown here The these three centers will collaborate with a worldwide network of rare disease experts to sequence the genomes of thousands of patients and their family members To identify the genetic variants responsible for rare genetic disorders As the coordination center of the university of washington group will coordinate the center activities that are essential for the program success And will host the sole web portal for sample solicitation The third component of our renewed genome sequencing program involves the creation of new clinical sequencing exploratory research projects Now for this six awards of the indicated amounts have been made to the indicated pi's Who will be investigating technical and ethical and psychosocial questions related to the application of genome sequencing in the clinic Note that the two awards with particular emphasis on cancer are being co-funded by the national cancer institute The fourth and final component of our renewed genome sequencing program involves grants for developing informatics tools for high throughput Sequence data analysis for this six awards have been made for a total of 16 million dollars over four years The goal of this program is to democratize access to next generation dna sequence analysis software so that independent researchers can analyze their own sequence data This program builds on previous investments that have been led to the development of nascent software tools But the grantees will work to harden the software tools to make them Reliable robust easy to install and user friendly for independent investigators and also for non-genomicists The pi's and funding amounts are shown here and also note that there'll be one or two svir awards eventually made as part of this program One highlight worth featuring from the genome sequencing program since the last council meeting is the recent publication Nature reporting the sequencing and comparative analysis of 29 euthyrian genomes The authors generated a high resolution map of more than 3.5 million Evolutionarily constrained elements that encompass about 4 percent of the human genome This study further used evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for about 60 percent of the constrained bases Overlap with disease associated variants indicates that these findings will be relevant for future studies of human biology health and disease The data sets for the study are publicly available at the Broad Institute and at the UC Santa Cruz genome browser The cancer genome atlas TCGA program held its first public scientific symposium in november All presentations uh described uh research using TCGA data The meeting was very well attended actually actually sold out Total capacity all the talks are available on NHGRI's genome tv channel of youtube and the link to those talks is provided in document 29 Based on the success of this meeting. There'll be a second TCGA scientific symposium in november of this year And aacr has agreed to co-sponsor and advertise the meeting along with nci and NHGRI In terms of its science TCGA continues to make great strides towards its ambitious goals The program had a goal of analyzing 5 000 tumor samples by the end of 2011 and they reached that goal Another goal is to comprehensively analyze specimens from at least 20 tumor types And the list on the right shows the active 22 projects in TCGA as of today accrual has actually closed for glioblastoma ovarian colorectal and renal cell renal clear cell carcinoma meaning the goal of qualifying 500 cases for these projects has already been achieved There are active tumor working groups preparing papers for publication for many of the tumor types including some of the most prevalent cancers A manuscript describing the full characterization of the colorectal carcinoma genome is under review and papers for breast lung and kidney cancer As well as acute myeloid leukemia are in preparation and are expected to be published by the end of 2012 Moving on to the thousand genomes project the phase one paper is being written on 1094 samples for 14 populations with 40 million SNP indel and deletion variants on integrated haplotypes The phase two data contained low coverage and exome sequence data on 1600 unrelated samples from 19 populations And the phase three sample collection from seven more populations should be completed by april All the sequencing should be completed by fall of this year on a total 2500 unrelated individuals plus 161 trios and or kids up within trios And complete genomics will deeply stepped in and will deeply sequence 500 samples including 161 trios So in total there are now 261 samples being studied by the thousand genomes project The eighth annual meeting of the advanced dna sequencing technologies program grantees will be held in april and san diego As in past years the last portion of the meeting will be open to other interested members of the research community And as i mentioned earlier, jeff schloss will be given an update about this program later today Moving on to encode and mod encode Applications were received in response to three technology development rfa's and these will be discussed during the closed session of this council meeting Three encode rfa's with uo one u 41 and u 54 mechanisms were released this past october And applications were received in december These rfa's aim to solicit applications for research projects to apply high throughput cost efficient approaches To extend encode resources towards as complete a catalog as possible Applications will be reviewed in march and then discussed by council in may And nhri is currently in the planning stages for a mod encode symposium to be held on the nih campus on june 20th and 21st Our goal is to broaden community understanding of model organisms and showcase the contributions of the mod encode consortium The meeting is planned to tie into the upcoming model organisms to human disease meeting Or that's being organized by the genetic society of america and scheduled at an adjacent time to our symposium here in the washington dc area Moving on to some of the analyses being performed by encode Um at the december janeva steering committee meeting there was a joint session including encode and janeva investigators Encode investigators analyzed eight janeva garnet g was data sets and they were paired up with janeva garnet investigators for hands-on Demonstrations of how to use encode data to follow up g was studies Our collaborate i'm sorry new collaborations between the consortium were established already resulting in plans for publications and grant applications Meanwhile several integrated analysis papers are in the works The encode consortium has a major integrative integrative paper under revision At a journal i mentioned earlier Along with many companion papers all of which are going to be aimed to be published in 2012 The mod encode consortium is working on a paper that integrates worm fly and human mod encode and encode data And the mouse encode consortium is currently planning a comparison of human and mouse encode data In our lc program the new return of results consortium is now active This is a consortium investigators conducting either behavioral social or normative research on ethical legal and social issues related to returning genomic results Including incidental findings to study participants or to patients in the context of clinical care The consortium includes investigators from seven r01 and r21 grants funded through the recent return of results rfa's Also includes lc investigators funded in the six uo one clinical sequence and exploratory research project grants As well as investigators on two other lc grants who are studying related issues The consortium aims to identify areas of possible consensus that can that can form the basis for policy development in this complex area Already plans are underway Among the investigators for sharing outcome measures and instruments Which should facilitate standardization and ultimately make it easier to compare data generated across studies The centers of excellence in genomic science sags and diversity action plan DAP programs held back-to-back meetings this past october at the dana farber cancer institute in boston This was our largest sags meeting to date with 10 active groups as usual. The science was outstanding We're actually hoping to bring the two sags groups whose grants are now ending to a future council meeting So they can share their experiences and results with council members The summary of the diversity action plan meeting has been provided under document 32 We will be discussing the most recent round of sags applications and the reviews during the closed sessions of this council meeting And the next receipt dates for applications to the sags program is may 17th And to the diversity action plan program is may 25th In december nhgi hosted a workshop on characterizing and displaying genetic variants for clinical action Dub the clin action workshop The workshop was a collaboration Between nhgi and the welcome trust and drew about 80 participants from a wide range of disciplines and organizations Including several nih institutes And centers also the centers for medicare and medicaid services cms and the food and drug administration The goal of the workshop was to consider processes databases and other resources needed to identify clinically relevant variants Decide whether they are actionable and what the action should be and provide this information for clinical use Videos presentations and recommendations from the working group are now posted on our website genome.gov and emmanus script describing the topics covered in the workshop is under preparation And a concept clearance for this area will be presented later today by terry menolia Also in december nhgi hosted a genomic medicine two meeting which built on the june genomic medicine one meeting That was presented at the last council meeting by jeff ginsberg and terry menolia This was the second of at least four planned genomic medicine meetings under the auspices of the new working group of this council The genomic medicine working group The meeting was attended by about 70 people The goals of the meeting were to develop ideas for multicenter collaborative pilot projects in translational genomic medicine To learn of new projects ongoing at potential partner sites and to identify infrastructure needs and solutions to speed the adoption of genomic medicine Six subgroups on topical areas were created and are now actively working and meeting in route to reporting Their findings and their recommendations at the next meeting Of videos presentations and recommendations from the workshop are now posted on genome.gov And a concept clearance about this area will be presented later today by terry menolia Now genomic medicine three meeting will be held in chicago in may and will focus on barriers to implementing genomic medicine programs And discussions with payers professional organizations and government regulatory agencies So that's what i want to say about the extramural program Let me move on and talk about updates for relevant nih common fund programs Starting with the molecular libraries program Now the molecular libraries program holds back 25 of each center's annual award for release based on demonstrated progress at the Mid-year point towards a set of year-end milestones And the four nhgi manage centers demonstrated good to excellent progress towards all milestones this year The mlp steering committee meeting occurs twice a year and the november meeting had individual presentations on center-driven research projects Funded as part of each center's u 54 grant These center-driven projects were added actually at the request of previous nih director alias sarhoony in 2008 Another key topic at this meeting was the development of a next generation database to advance chemical biology data and analysis Beyond the currently though that currently provided by pub Development of this molecular library's biological database will be supported through grant supplements to several of the mlp centers The cop program Came to an end in september, but there are some no cost extensions to cover wind up or wind down activities The comp finale and comp to kickoff meeting was combined with an international mouse phenotyping consortium meeting in september For comp two awards were made in fiscal year 2011 With overall funding for the program being 111 million dollars over five years The goal is to produce and phenotype 2500 mouse strains Three centers that had submitted paired Mouse production and mouse phenotyping applications were funded as shown here on the slide One application was funded for the data coordination center and database at the ebi um The g-tex project genotype tissue expression project their investigators had their third in person meeting in december At the point when the pilot phase of the project was roughly half complete I will tell you that there's been excellent progress in meeting the milestones for the pilot phase Especially with respect to donor enrollment as shown in the bar graph Specifically the program is averaging 10 donors per month with the current total number approaching 100 And note that the pilot phase target is 160 Also the resulting quality of the purified d rna from the rapid autopsy tissues has been quite good actually very good Essentially at the proposed target levels The external scientific panel who I actually met with during this meeting was actually quite impressed and very supportive Of this pilot phase of this common fund project And so a proposal for scaling up the project to include an additional six to 800 donors Is being developed and would be submitted to the common fund group shortly for possible fiscal year 13 funding The library of integrated network based cellular signals our signatures program held a consortium meeting in october with members of the production centers As well as newly awarded collaborative supplement technology development and computational tool awardees The external advisory panel members for the project were also in attendance and provided several recommendations Including developing a transcenter project between the u54 and uo one groups Creating a public data release policy and also defining metrics for the program The links centers have created a public website to inform the community about the links program as well as to describe the data available Through their respective centers websites But also to discuss current experimental components of the program and to update users on new developments in the links program NIH staff is in the process of developing a plan for bridge funding for links in fiscal year 2013 And the proposals being coordinated with the common fund and should be finalized shortly As recommended by the external advisory panel NIH staff is currently developing language for a data release policy for the program Which will include input from the links The links production centers Next common fund project protein capture reagents program And for this program the newly funded grantees of the antibody production and technology development center Which comprises the protein capture consortia met for a kickoff meeting in december Accomplishments of the meeting included formation of working groups to complete certain tasks and the development of a public portal to access The affinity reagents in addition NIH staff put together an external scientific panel comprised of five members with appropriate expertise for the program This panel has a chance to make initial suggestions during the december meeting and NIH staff is planning a follow-up conversation in the coming months Human heredity and health in africa or h3 africa common fund program What I can tell you is that applications for all four rfa's Rfa's on developing centers research projects bio repositories and bioinformatics network We're all received in december and we were extremely pleased with the response. In fact, we would rate it as excellent In terms of the number and depth and breadth of applications The initial review of these applications will be in march while the second level review will be at this council meeting in may The biorepository rfa was reissued for some technical reasons and the due date is in february Now remember that h3 africa is a joint venture between the nih common fund and the welcome trust And the welcome trust application process is proceeding well and is on a similar timeline And finally an important meeting was held in november in nigeria called ethics and genomics research in africa or eager africa At this meeting a group of bioethicists researchers policymakers and representatives From various african countries and the united states and the uk gathered to discuss the ethical conduct of genomics research in africa These deliberations will form some of the broader plans for h3 africa For the common fund's new single cell analysis initiatives new rfa's were published since our last council meeting They were in the following areas studies to evaluate cellular heterogeneity using transcriptional profile in a single cells exceptionally innovative tools and technologies for single cell analysis And accelerating the integration and translation of technologies to characterize biological processes at the single cell level Applications were due in late january And finally among the new areas chosen for a potential future common fund initiatives is disruptive proteomics technologies This potential initiative was proposed during the solicitation for potential new common fund programs last summer for funding in fiscal year 2013 the institute and center directors endorsed this idea. So the common fund is moving forward in developing this program nigms and nyhi have been asked to co-lead this effort A trans nyhi working group has been established including tina gatlin and adam felsenfeld from nyhi And a strategic planning process is underway, which includes a portfolio analysis and gathering community input A proposal for the program by the working group is due in late april And if approved for further consideration then a concept clearance will be brought to the common fund's council of councils at their June meeting Meanwhile early planning for new common fund programs that will begin in fiscal 2014 have just started And now we'll have more to say about these efforts at a later council meeting So that covers the common fund and let me move on now to talk about updates from the nyhi office of the director The first is that the nyhi g was catalog Continues to to curate g was data from the published literature by personnel within our office of population genomics That curation effort now accounts for 1615 Associations for roughly 250 traits at p values less than 5 times 10 to the minus 8 As of january of this year the catalog had reached over 5600 associated snips snips with p values less than 10 to the minus 5th Recently two new columns of information were added to the g was catalog mapped gene and snip context If you click on one of the links under the map gene column, for example, you are taken to a relevant entree gene page These fields are a result of continued collaborations with ncbi to improve the quality of data that are made available to the scientific community And a collaboration with ebi has also been recently initiated to add curation expertise to the catalog team And to make informatics improvements such as automating the catalog diagram and standardizing trait names to the ontology 13 articles have now been published as part of the new england journal of medicine genomic medicine series edited by greg fero and ellen guttmacher There are a total of 14 articles planned for this series total And shown here the latest four articles published since the last council meeting The second annual or the second usa science and engineering festival will take place on april 28th and 29th of this year at the washington convention center As with the last festival held in october of 2010 nhgeri will be heavily represented as nih representatives with booths for hands-on Activities and as a result you can expect that many many many strawberries will be sacrificed in pursuit of their dna This year we will be partnering with the american society of human genetics to have joint activities as part of this festival Greg fero chairs a trans nih working group charge with exploring trans nih collaborations on family history research And my family health portrait related activities Meanwhile, jeff ginsburg and lori orlando co-chair in nhgi organized Working group on family history as part of our broader extramural genomic medicine planning efforts nhgi is collaborating with suburban hospital here in Bethesda and the johns hopkins university school of medicine to hold A monthly grand round style seminar covering topics in genomics medicine genomic medicine Greg fero is leading the planning committee for this series, which will run from last december to this coming june All the talks are being videotaped and we've made available on nhgi's genome tv channel of youtube A meeting to explore the genomic opportunities for studying sickle cell disease was held last december in california While nhgi was the lead organizer We partnered with several other nih institutes including nhlbi, nychd, nyddk nymhd, nynds I'm sure everybody knows exactly which institutes those were heart, london blood, child health Diabetes digestive kidney diseases minority health and neurological diseases. How's that for the meeting? um This meeting was co-chaired by michael debon richard gibbs and julie mcconnie from tanzania Attendees included council members rick wilson There was general enthusiasm from the participants for accelerating research into sickle cell disease Using genomic approaches The discussion also emphasized the fact that attention needs to be paid to the appropriate selection of samples and to phenotyping And the participating nih institutes are continuing discussions to explore flute future contributions in this area Late last year the genomic health care branch in collaboration with grace quo Held a meeting on pharmacist education in the era of genomic medicine that included representatives of major us pharmacy organizations and howard i think you were at this meeting council member howard there's a picture somewhere Oh, yeah the back back row there is the meeting discussed pharmacist education in genomics and identified a number of priorities to pursue And the meeting summary will be forthcoming in the near future And finally in truly am winding down here last the nih nhgi's intramural program Let me just remind you I mentioned at the last council meeting that nhgi intramural research program is undergoing a blue ribbon panel review The last one was held in 2001 and in fact, they're supposed to happen once a decade So we're right on target having one now and shown here is the panel's membership Note that rick meyers is the representative from council on this blue ribbon panel on the first meeting of the blue ribbon panel occurred last month And was extremely helpful and informative. I think was a good kickoff to this process The future steps for this review all of which is going to be taking place within about a nine month interval Will be a conference call coming up later this spring and then a final in person meeting that we're trying to schedule in july So where we're heading for this relevant to this council's I've delayed an update about our intramural program Which normally would take place about this time But decided to delay it and in fact we'll even delay it past may we'll wait until september And then at the september council meeting we will have a presentation about nhgi's intramural research program by the new Scientific director by then he won't be so new anymore. In fact, he's not that new even now dan castner Who's our scientific director, but I haven't had to present to council yet I think we should just wait until the fall I'll have him present and then rick meyers will be presenting the the report from the blue ribbon panel As a member of that panel to council so we'll do both of those things in september in terms of recent research highlights From nhgi's intramural program Would include the following these just a few of many highlights Adan castor our scientific director and colleagues published a study in the newland journal Identifying it's the genetic mutation that causes cold temperatures to trigger trigger allergic reactions a condition known as cold eutycaria In addition to pointing the way towards a potential cure this finding provided new insights about immune system function your data samuels and an nyh led team studying the genetics of Melanoma reported a very nice of finding a nature of genetics about a new gene that's been implicated in the pathogenesis of melanoma And less besicker and colleagues at the and colleagues including at the nyh intramural sequencing center at the children's national medical center at Johns Hopkins university published a nice paper in the american journal of human genetics that reported the use of next generation genome sequencing To identify a gene mutated a pediatric condition known as paroxysmal nocturnal hemoglobinuria And at last may's council meeting i mentioned that bill gall who's nhgi's clinical director and founding director of the nyh Undiagnosed diseases program was one of nine finalists across the entire federal workforce To receive the samuel j hyman service to america metal from the partnership for public service And i'm very proud to tell you that not only is he a finalist He actually won the award in the category of science and environment These awards are known as sammie awards and they pay tribute to members of the federal workforce Highlighting those who have made significant contributions to our country Honorees are chosen based on their commitment and innovation as well as the impact of their work and addressing the needs of the nation And so we're very proud of bill gall and his accomplishments and congratulations to him And finally i should tell you that's the end of what i want to update you about but everything i've just covered in 90 slides Was trivial as far as i'm concerned because the highlight Since the last council meeting Occurred not here at nyh, but occurred on the baseball field So I know rick wilson agrees with me either maybe some other car that hired a cardinal fan These this was the most historic thing that happened in the last four months. Um, no any case No, no nothing this has to Number one historic event in the last four months and in closing I 91 slides. I don't put these all together all by myself Whole hosts of people everybody sit in the back on the sides and so forth. Thank all of you Thanks, particularly to chris wetterstrand who is the person coordinating all this and making it all happen And also to larry thompson judy white and the web team for getting all this posted and all the videotaping and everything that goes on So I will stop there and happily take any questions I must be getting good I just wanted to get to the cardinal highlight. I was just really motivated question Do I the one thing I didn't stop in the middle do any of um Any of the workshops or things that council members participated in I don't know if rick wilson wants to any about the sickle cell Meeting of jill you want to say anything about the working group? Howard you want to say anything about the pharmacy meeting? Um rick you want to say anything about the blue ribbon panel? I didn't you know, we don't have to because we're going to come to these things with time But I just if there was something that was particularly you wanted to share microphone I would just want to encourage people to Respond to the call for information for working group. I can't really say any more than that But I would also say that the tcga meeting was phenomenal. It was it was really a great great meeting We hear this from lots of people. Thank you for sharing that. It was terrific. Yeah, and I really I Be said it you echoed it. Let me let me echo it again Please people respond to the call for information because we are in need of input Yeah, we'll send it to you. Well, it's a link but we can we can send you an email And I would also say that it's important to say What you think are important things To be done and also important Not to be done You know what what is possible and should be done What is likely impossible And effort might be better Spent somewhere else there's this is a challenging area and both The internal discussions and I think the external discussions have had a lot of challenges of just defining the scope of what's realistic And so I think that's part of what's being requested And it's so and yet it's so vital for our field for this institute. It's really vital for NIH, of course So yes, I really do we really would hope people would get engaged in this process to help and I'm sure there's going to be Things coming back to this council about it. So it's no question. So it's worth getting involved early Howard So the privilege of being at three and inch URI meetings in in five days in early december Which I I can't feel bad because you had to be at all those and more so but Whether it was the pharmacy group or the genome medicine centers group or whatever the terry called the one in between Clean action the clean action group. Um, all of them What really struck me is that not only is there a lot of enthusiasm about moving to the right side of the NHGRI In this GRI gram, but there's a lot of people who didn't know what NHGRI stood for and We're outside of that space who are now starting to realize that there's something to work on. So I think What I took away was not only do we have to be more visible But really there's a lot of need now the disease specific groups not so much at NIH but out in the community Really need a lot of help And so it was great to see how much you guys are cranking up for that including reaching out to people like pharmacists and Nurses and their fresh practitioners, etc But there's going to be a lot more of that needed. So I think we need to keep our eye on it Okay Echoing the same thing for this Geneva in code meeting In code we've known that lots of people who might be able to use the data don't even know about in code So this it was just the initial one and I don't remember the number of groups, but there were a lot of people Sorry, I think I think they all felt well, I certainly thought it was good to try to get these two together and I've had Responses from some of the GWAS, you know for the people who didn't know about in code Getting back to me after that meeting because they're saying that we really need to be able to do this So I think that needs to be expanded dramatically. It was it was really valuable I thought well, we would also look to you know, your advice when there are opportunities to connect Different groups together. I mean that was an example where was that came up that connect two of our consortium together When there are other situations like that and we can facilitate it. We will I don't know if the council member everybody knows how this was done, but they they would NHGRI paired Analysis folks with some of the from in code with some of the folks who had the GWAS problems and They worked ahead of time before they came to the workshop and there were a number of things that certainly that came out of that That was a really clever way to do it Other comments or questions? Yeah, okay, so we're scheduled for a break. I think everyone I hope everyone received mark's email about food You know if you go one floor up you can get coffee something to snack on there Please be back no later than 11 and we're going to be serious about this I'm sorry. I can't there's a glare on the floor So 10 o'clock so we have adequate time for the presentations