 Thank you, Rudy. Again, let me welcome all of you to this open session. Not only those of you in the room, but those of you joining us remotely, either live or will be joining us later by watching the video cast of this open session. My director's report presentation, as you know, will be videotaped and that recording will be made part of a permanent archive on NHGRI's website, genome.gov. And for those of you who are new to council and that includes some of our council members, I want to make you aware of the electronic resource that is established routinely from my director's report, something analogous to a supplemental materials of a published paper. And this resource can be accessed at the URL shown on the slide. The slides that I show during my director's report are also available electronically, already posted, available, both in a PDF format or a PowerPoint format. Meanwhile, while there'll be documents or relevant websites associated with a particular slide, you'll find a document number indicated on the bottom right of the slide indicated, which points to material that can be accessed or downloaded from the website shown here. This dedicated website and all the associated documents will be archived on genome.gov as a historic record of this meeting. Now, there'll be a number of presentations during the open session of this council meeting. My director's report is going to be sort of tailored around these presentations. I'm really not going to discuss in detail the topics that others are going to cover. But this will start immediately after my director's report by a presentation given by council member Jeff Botkin, who's going to give an annual report of council's Genomics and Society Working Group. Jeff is not going to sit down after that presentation, but rather he will then immediately present a report of the National Academy of Science, Engineering and Medicine entitled Returning Individual Research Results to Participants' Guidance for New Research Paradigm. Then we'll get a lunch break. And after lunch, Adam Falzenfeld will present a set of concepts for the Human Genome Reference Program for which we are seeking council's approval. And then finally, Terry Minolia will present the annual report of another one of council's working groups, the Genomic Medicine Working Group. So for the rest of my director's report, I'm going to break things down into these seven categories, which we have found nicely provide a framework for covering the topics that we think are important to cover. And I'm going to start with some general NHGRI updates and we'll start with a retirement. So NHGRI Extramural Program Director, Lita Proctor, will retire at the end of this month. Lita came to NHGRI in 2010 to lead the institute's effort in managing the first phase of the Human Microbiome Project. Lita has been instrumental and integral to the success of that project, including its transition to a second phase and its ultimate completion. I would point out that the Human Microbiome Project is often cited as an exemplar NIH Common Fund program. It has also helped to establish an advanced microbiome research at the NIH more broadly. Lita will actually stay on as a volunteer to guide the completion of some additional Human Microbiome Project publications. And so we thank Lita and we certainly wish her the best of luck in navigating the world of retirement. Another extramural program director, Vivian Oda Wang, is also departing NHGRI, not retiring. Rather, Vivian is moving to the National Cancer Institute to fill a newly created position, the Deputy Director of the Office of Data Sharing, where she will work to promote broad and robust sharing of human and non-human data from a wide range of genomic studies. While at NHGRI, Vivian served as a genomic data sharing program administrator and also chair of the Institute's Data Access Committee. She has also been involved with trans-NIH and NHGRI data sharing policy development and the submission management and oversight of data access and sharing for the Institute. Previously, she served as a program director in NHGRI's LC research program. Well, needless to say, we wish Vivian all the best with her new pursuits at the National Cancer Institute. Now, for now, with that as a void, Barbara Thomas is stepping in. She'll be taking over Vivian's responsibilities of chairing the NHGRI Data Access Committee and serving as the program administrator that assists applicants and grantees with the development of appropriate data sharing plans associated with their grants. This interim responsibility will be on top of Barbara's day job of managing all aspects of the applications submitted to the Center for Inherited Disease Research. And we thank Barbara for taking on these extra responsibilities on an interim basis. As you just heard in the introductory comments from Rudy, we have some new arrivals. One of them I want to emphasize is Lisa Chadwick, who recently joined our extramural research program as a program director in the Division of Genome Sciences. In addition to managing an investigator-initiated grant portfolio, she'll be working on the Centers for Mendelian Genomics Program. Prior to coming to NHGRI, Lisa worked in the Division of Extramural Research and Training at the National Institute of Environmental Health Sciences, or NIEHS, where she was among the leaders of the Roadmap Epigenomics Program and the 4D Nucleum, both NIH Common Fund efforts. Her scientific background is in complex trait genetics, epigenetics, and chromatin biology. She received a PhD in genetics from Case Western Reserve University and did postdoctoral research in the Division of Intramural Research at NIEHS. So we're pleased to have Lisa join NHGRI's extramural program. Around other parts of the Institute there are also some new faces, or will be some new faces. NHGRI's Division of Policy Communications and Education partners with the American Society of Human Genetics, or ASHG, in sponsoring two fellowships each year. The Genetics and Public Policy Fellowship program provides fellows with an opportunity to work in NHGRI's Policy and Program Analysis Branch, also at ASHG and also in the U.S. Congress. This year's fellow is Eve Granitowski. Eve recently earned her PhD in Biochemistry from the University of Notre Dame. Meanwhile, the Genetics and Education Fellowship program provides fellows with an opportunity to work in NHGRI's Education and Community Involvement Branch and also at ASHG in developing educational programs for a wide range of audiences. The fellow may also rotate in a public or private organization involved in genetics and genomics education. This year's fellow is Diana Christopher. Diana recently earned her MPH in genetics from the University of Pittsburgh. Another fellowship program is one that NIH and the American College of Medical Genetics and Genomics, or ACMG, sponsor. This is a fellowship in genomic medicine program management. This fellowship involves a collaboration among five NIH entities, NHGRI, also the National Heart, Lung and Blood Institute, the National Institute of Mental Health, and National Institute of Minority Health and Health Disparities, as well as the All of Us research program. Now, the goal of this NIH ACMG fellowship is to increase the pool of physicians trained in managing research and implementation programs in genomic medicine. Up to two qualified physicians can be selected annually for a 24-month training opportunity to acquire credentials and experience in leading genomic medicine research and implementation programs at NIH, at major medical centers, and at other organizations. And we encourage applications for this two-year fellowship, which are due annually on December 1st. Now, by way of reminder, in February at the February Council meeting, NHGRI kicked off a new round of strategic planning, which has been dubbed Genomics 2020, because we aimed to publish a new strategic plan in the fall of 2020. This process is now in full swing. To date, NHGRI has held two traveling town halls, one in June in Seattle, Washington, and one in July in the California Bay area. You'll remember, remember, that we also held a virtual town hall in May that was conducted entirely online and on the phone. With the process, we're now starting to shift gears a bit in our strategic planning. Our first three town halls that I just mentioned and some other initial events were more open-ended discussions about the future of genomics. And from this point forward, we plan to include additional opportunities for participants to provide feedback about some of the ideas that have emerged from the earlier discussion. This will allow NHGRI to begin focusing the conversation so to help advance nascent ideas to become more mature plans. This shift will be evident at our next town hall, which actually takes place in Atlanta, Georgia this coming Wednesday. In addition to that town hall, we will host an ancillary session at the American Society of Human Genetics, or ASHG, meeting on the evening of October 16. More information about the various upcoming strategic planning events can be found on the Genomics 2020 website, which you would find at document number three. NHGRI, along with three other NIH institutes, the National Heart, Lung and Blood Institute, National Institute of Minority Health and Health Disparities, and the National Institute of Diabetes and Digestive and Kidney Disorders, as well as the FDA Office of Minority Health continued the genomics and health disparities lecture series with two speakers this fall. John Carpton, formerly actually an investigator in NHGRI's Intramural Research Program, but who is currently chair of the Department of Translational Genomics at the University of Southern California, spoke about the role of population diversity in cancer genomics. And that seminar took place in August. And then Esteban Bouchard, professor of bioengineering and therapeutic sciences and medicine at the University of California in San Francisco, gave a lecture earlier this month that discussed how to make precision medicine more socially precise. Now this series is part of an ongoing dialogue about how innovations and genomics and technology can affect health disparities. All lectures in the series are video recorded and made available on NHGRI's Genome TV channel of YouTube. This past July, the Southwest, I'm sorry, the South Central Foundation and the Alaska Native Health Board co-sponsored a multi-day workshop in Anchorage, Alaska that focused on Alaska Native priorities and interest in participating in genomics and other clinical research activities. Sponsored by NIH, this gathering included participation by Alaska Native leadership and community members from across the state of Alaska. It included NIH grantees and researchers working with Alaska Native communities, as well as representatives from eight different NIH institutes and centers. The forum was also an opportunity to build relationships and provide information about recent scientific and medical advances, as well as those on the horizon. And the idea was for ideas for future research to be explored, recognizing the importance of meaningful partnerships, sustained engagement, community-directed priorities, and most importantly, perhaps respect for tribal sovereignty. The workshop ended with a commitment to continue to explore opportunities for genomics research relevant to the concerns and direction of Alaska Native people. With that, I'll move on to some general NIH updates, and once again, we are facing some retirements. So, for example, last month, Pat Grady retired as the director of the National Institute of Nursing Research, or NINR, after holding that position for more than 23 years. Pat came to the NIH in 1988 when she joined the National Institute of Neurological Disorders and Stroke, or NINDS, as a program administrator in the areas of stroke and brain imaging, ultimately serving as NINDS's deputy director and also as acting director. In 1995, Dr. Harold Varmas, then the NIH director, appointed Pat as the director of NINR. Among her notable accomplishments are strong advocacy for interdisciplinary science, developing research programs to understand the symptoms of fatigue and pain, and improving care to those at the end of life. And Kashan will serve as the NINR acting director while NIH conducts a search for a new director. In addition to goings are also some comings, and we have a new identified institute director, on this case, a center director. In November, Helene Langevin will become the new director of the National Center for Complementary and Integrative Health, or N-C-C-I-H. Dr. Langevin comes to the NIH from the Osher Center for Integrative Medicine, jointly based at the Brigham and Williams Hospital and Harvard Medical School. Her research interests have centered around the role of connective tissue and lower back pain, and the mechanisms of acupuncture, and in manual and movement-based therapies. The NIH strategic plan for data science, which was actually requested by the US Congress, was published in June. This important document aims to provide a roadmap for modernizing the NIH-funded biomedical data science ecosystem. The plan includes five overarching goals that focus on establishing modern and effective research data infrastructure, modernizing the data resources ecosystem, supporting the development and dissemination of advanced data management, analytics, and visualization tools, enhancing data science workforce development, and enacting appropriate policies to promote stewardship and sustainability of data resources. Now, working groups across the NIH have begun discussing implementation tactics for each of these goals and objectives laid out in the strategic plan, and further updates about the plans implementation will be provided at future council meetings. In a related development, in July, NIH launched a new initiative called the Science and Technology Research Infrastructure for Discovery Experimentation and Sustainability, or STRIDES. The initiative will start with developing a cost-efficient framework for NIH-funded researchers to use the Google Cloud platform. Specifically, researchers at more than 2,500 academic institutions across the country who are receiving NIH support will be able to make use of the Google Cloud storage computing and machine learning technologies. The STRIDES partnership involves a collaboration with the NIH Data Commons pilot and will involve training researchers at NIH-funded institutions to use the Google Cloud platform. Now, STRIDES is starting with Google Cloud as its first industry partner, but it's expected that additional industry partnerships will be formed in the future. On to budget. Well, at September 18th, the Senate overwhelmingly approved a fiscal year 2019 appropriations bill that will fund the Department of Defense as well as labor education and health and human services, which NIH falls under. This bill was then sent to the House, which was out of session last week, but is expected to approve the bill this week. Once this occurs, it is off to the President to sign. The remaining discretionary government funding that has not been approved prior to the start of the new fiscal year on October 1 will fall under a continuing resolution that ends on December 7th. Now, the notable feature of these developments is that it seems almost certain that NIH will have its budget in place at the start of fiscal year 2019, that is on October 1st. Such a logical and same circumstance for the start of a fiscal year has been exceedingly rare in recent years, and so we are overwhelmingly excited about fiscal year 2019. This is compounded by the actual numbers associated with the NIH fiscal year 2019 budget. So shown here are the relevant numbers for the Labor Health and Human Services Appropriations Bill from fiscal year 2018 in the second column, and those passed by the Senate last week in the third column. Note that NIH will likely receive a $2 billion increase in fiscal year 2019, shown in the fourth column, reflecting a 5.1 percent increase shown in the fifth column. The new bill has set aside almost $800 million of the $2 billion increase for specific areas of emphasis, including Alzheimer's disease research, cancer research, the brain initiative, and the All of Us Research Program. Now, assuming the House passes the bill and the President signs it into law, NHGRI's budget would increase to $575 million in fiscal year 2019, which would reflect a $19 million or 3.3 percent increase. We are obviously extremely appreciative of Congress's increasing support of NIH and NHGRI. So, that wraps up the NIH updates and the NHGRI updates. Let me move on now to some general genomics updates. Population geneticists known to many of us, Luca Cavalli-Sforza, died, unfortunately, on August 31st at the age of 96. Luca was best known for his extensive statistical and genetic work on human evolution. He worked with evolutionary biologist Mark Esteldman on the gene culture evolutionary theory, which states that human behavior results from an interplay of genetic and cultural evolution. Several genomicists are among the 19 scientists selected as new investigators of the Howard Hughes Medical Institute. These include Drs. Howard Chang, Beth Shapiro, and Fang Zhang. Congratulations to all of them. And then, in terms of genomes in the news, we always like to tell you about the recently generated genome sequences that have been reported since last we met at a council meeting. These include the koala, the English oak, and the water fern. And in addition, the vertebrate genomes project, which some of you may be familiar with, has gained quite a bit of traction, and they reported the generation of 15 new high-quality reference genomes from the following, the flyer cichlid, the Eastern happy, the climbing perch, the tire-track eel, the blunt snouted clingfish, a male and female zebrafinch, Anna's hummingbird, the greater horseshoe bat, the pale spear-nosed bat, the two-line Sicilian, good store-and-scrub tortoise, Canada lynx, one of my favorites, the duckbill platypus, and the cacopo. So, continued progress in comparative genomics. Moving on then to our institute's extramural research program, and starting with the genome sequencing program. So NHGRI's genome sequencing program, or GSP, is composed of a coordinating center, four centers for common disease genomics, four centers for Mendelian genomics, and three analysis centers. The entire program is supported by multiple organizations in addition to NHGRI, including the National Heart, Lung, and Blood Institute, the National Institute of Aging, National Eye Institute, as well as the Simons Foundation. Now the centers for common disease genomics have generated over 63,000 whole genome sequences and over 57,000 whole exome sequences. A second data freeze will occur in the next month or two in conjunction with NHLBI's trans-omics for precision medicine freeze-5, comprising approximately 100,000 whole genome sequences. Highlighted here is an August publication, which stems in part from the program's cardiovascular disease working group. In this publication, Kerro and colleagues developed polygenic risk scores from about 6.6 million polymorphisms and were able to identify strata of individuals with fourfold increased risk for coronary artery disease. The authors observed similar patterns in breast cancer and severe obesity. Now this paper nicely illustrates the opportunities and challenges of using polygenic risk scores in routine clinical care. Meanwhile, our other major centers program, the centers for Mendelian genomics, continue to have high levels of disease gene discovery in a strong publication record. Highlighted here is a June publication from the Baylor Center describing a novel approach for predicting which genes are susceptible to ALU-ALU-mediated re-imagements. ALU-ALU copy number variants are estimated to be responsible for about 0.3% of human genetic diseases and the approach described in this paper has been incorporated into a computational tool that is available to the research community. Now the genome sequencing program analysis centers aim to undertake novel investigator-initiated analyses of the data produced by the other centers. The analysis centers harmonize functional annotations and design novel computational tools and methods. In collaboration with council member Dan Roten and other emerge investigators, the Vanderbilt Analysis Center, developed phenotypic risk scores. Such risk scores reflect the degree to which individual symptoms overlap with patterns indicative of a Mendelian disease. The study also involved incoming council member Nancy Cox's work. In a study using the clinical features of 1,204 Mendelian diseases, investigators were able to distinguish cases versus controls for given Mendelian diseases and uncovered 18 associations between rare genomic variants and severe phenotypic outcomes. Phenotypic risk scores can augment the interpretation of rare genomic variants and may identify subsets of patients with genetic causes for common diseases. Other activities within the genome sequencing program include investigator-initiated work to generate high-quality human and non-human primate reference genome sequences. The two groups that NHRI funds in this area recently published this paper, which was a high-resolution comparative analysis of chimpanzee, orangutan, gorilla, and human genome sequences. They estimate that 83 percent of eight genomes can now be compared in a multi-sequence alignment, which facilitates identifying structural variation and human specific variation. This paper also describes 1700 fixed human-specific structural genomic variants identified using a contiguous reference free genome sequence assembly method. NHRI's technology development program continues to pave the way to develop new and improved technologies to enable genomic discoveries and facilitate the adoption of genomics in medicine. An advanced genomic technology development meeting was held at Northeastern University in May. Novel nucleic acid sequencing and genomic technology grantees met over several days to facilitate communication, collaboration, and interaction. Meanwhile, an adjacent public meeting provided broader community participation and allowed NHRI to gather feedback about genomic technology development as part of our broader strategic planning process. The next meeting of this group is planned for May 29th to 31st of next year. Now, there are two upcoming funding opportunities that deserve mention related to our technology development efforts. Program announcements for novel genomic technology development are resulting in a wide breadth of submitted applications and funded grants with areas of study ranging from advanced tools and critical reagents to the development of epigenomic and genomic profiling assays. The next application due date for this area is in early October of this year. Now, building on the success of the previous funding announcement, NHRI is again soliciting applications for novel nucleic acid sequencing technology development that involve both DNA and direct RNA sequencing. And the next application due date for this area will be June 27th of next year. Moving on to ENCODE, the goal of the Encyclopedia of DNA Elements or ENCODE project is to create catalogs of all functional elements in the human and mouse genomes and to make those catalogs available as a resource to the biomedical research community. ENCODE data continued to be used widely as of August of 2018. NHGRI has identified more than 2,200 community publications shown by the red curve from groups without ENCODE funding but who used ENCODE data for their published work. ENCODE consortium members have produced more than 1,000 publications shown by the blue curve. The use of these ENCODE data attests to the broad value of the resources being produced by this program. Nicely illustrating the value of ENCODE data is a recent study that investigated the genetic contribution of adult onset Alzheimer's disease. The paper reported the presence of a common haplotype that appears to confer protection from the disease. The authors found that some of the genomic variants on that haplotype may influence genome function in myeloid cells regulating the transcription factor PU1 as well as downstream targets of that transcription factor. Now part of the generated evidence for this finding came from the use of data from the ENCODE and roadmap epigenomics projects as well as the tool haploreg which mines ENCODE, epigenomics, and 1000 genomes project data. NHGRI's new variation function and disease program supports the development of novel and generalizable approaches to study how genomic variants lead to differences in genome function, how such functional differences affect human health and disease processes and how that knowledge can be used clinically. NHGRI recently released two program announcements to support investigator-initiated research on novel approaches for relating genomic variation to function and disease. The first receipt date is October 5th for R01s and October 16th for R21s. Our Centers for Excellence in Genomic Science or SEGs program supports interdisciplinary research teams to develop highly innovative approaches in genomics research. Two new SEGs awards remain this year bringing the total current total of Centers to nine. The Center for Subcellular Genomics is led by Jun Young Kim of the University of Pennsylvania. Using neurons as a model system this group will study complex genomic interactions in single cells by developing new optical and nanotechnology approaches to examine subcellular components. Of note the National Institute of Mental Health is co-funding this award. The Center for Synthetic Regulatory Genomics is led by Jeff Buca of New York University. This group will develop and apply methods for making large DNA fragments and integrating them into cells which will enable study of regulatory sequences distant from the genes that they affect. The next annual receipt date for SEGs applications is May 20th of next year. The Electronic Medical Records and Genomics or Emerge Network conducts genomic discovery and clinical implementation research by leveraging data from large biorepositories linked to electronic medical records. Recently Emerge Investigators published three major articles on the Informatics Science and LC components of the network. The first article entitled Empowering Genomic Medicine by establishing critical sequencing result data flows the Emerge example describes Emerge's experience with the delivery of consistent machine readable genetic and genomic sequencing test results from multiple laboratories to multiple healthcare provider organizations by establishing a common transfer format and implementing transfer mechanisms. The second article entitled Transcription Factors operate across disease loci with EBN-A2 implicated in autoimmunity demonstrates a molecular mechanism for how the Epstein-Barr virus nuclear antigen 2 or EBN-A2 super enhancers interact with transcription factors thereby contributing to the development of several autoimmune conditions. The third article entitled Physicians Perspectives on Receiving Unsolicited Genomics Results reports physicians concerns about the actionability of unsolicited genomic results as well as the impact on patient well-being, impact on healthcare workflow and the medical and ethical responsibilities of returning unsolicited genomic results as illustrated by the table shown on the right. The Clinical Genome Research resource or ClinGen evaluates and disseminates the clinical relevance of genes and genomic variants for use in precision medicine and research. This includes determining the extent to which various genes are associated with hereditary disorders. ClinGen's Cardiovascular Disease Working Group formed a gene curation panel focused on Brugada syndrome, a serious genetic condition that causes disruption of the heart's normal rhythm and predispose a patient to sudden arrhythmic death. This panel, chaired by Michael Gallop at Toronto General Hospital, published the results of their extensive curation of the 21 genes implicated in this syndrome in the journal circulation. The group found that only one of the 21 genes typically tested for Brugada syndrome, that is SCN5A, has a definitive disease association, while the remaining 20 genes, several of which are highlighted here, are classified as disputed. These surprising findings were highlighted in several press releases, including from the Sudden Cardiac Arrest Foundation. The detailed curation reports are available on the ClinGen website. With over 30 groups performing gene and genomic variant curation, ClinGen continues to standardize the processes of evaluating genes implicated in disease, ultimately leading to improved clinical test development, more accurate result interpretation, and higher quality patient care. The clinical sequencing evidence generating research or CSER program now in phase two aims to generate evidence related to clinical utility of genome sequencing, with a major emphasis on recruiting ancestrally diverse and medically underserved populations. In this table, racial and ethnic diversity refers to participants of non-European ancestry, whereas total diversity also includes populations with a lack of access to primary care services. For example, to contribute to CSER's overall aim of studying genome sequencing in racially diverse populations, the ClinSeq component recruited a cohort of 500 volunteers who self-identified as African-American or Afro-Caribbean. This month's American Journal of Human Genetics features a marker paper describing CSER's phase two, reporting the patient populations to be studied and scientific goals of the consortium. The paper was a collective effort of investigators from the CSER sites listed on this table. Now, during the initial months of CSER's phase two, investigators focused on proposing harmonized measures that will be disseminated to participants recruited by the CSER clinical sites. These measures are now available on the CSER website. Baseline adult and parental patient survey measures include demographics, access to care, literacy and numeracy, insurance status, income and quality of life ascertainment. These materials will be translated into Spanish to accommodate participants whose first language is Spanish. The groups are also finalizing return of results and follow-up measures for participants and providers. CSER has also harmonized measures for capturing the reasons for declining participation as well as writing this to change within healthcare systems. CSER has also been actively engaging stakeholders such as community members and patients and providers at each site and across the consortium. In conjunction with its in-person scientific meeting earlier this month, CSER held a half-day stakeholder engagement meeting which convened pairs of investigators and stakeholder buddies from each site. To prepare for the meeting, these pairs of investigators and stakeholders defined and discussed key issues of importance to the stakeholders. The meeting explored participant and researcher perspectives on research topics of interest to CSER such as family communication, identification of unmet needs from the healthcare system and personal utility. The meeting also identified better ways to engage stakeholders across CSER and the generated suggestions are now being considered by the various CSER working groups. The newborn sequencing and genomic medicine in public health or NSITE program explores in a limited but deliberative manner the implications, challenges and opportunities associated with the possible use of genomic sequence information for care of newborns. In August, NSITE studies were highlighted in a Hastings Center special report entitled The Ethics of Sequencing Newborn's Reflections and Recommendations. Now in the lead article entitled Sequencing Newborns a Call for Nuanced Use of Genomic Technologies, the UCSF NSITE Ethics and Policy Advisory Board recommends the diagnostic use of targeted or whole genome sequencing to inform medical management of symptomatic newborns while arguing that genome sequencing is not yet ready for use in universal screening programs such as newborn screening. 12 additional articles which are listed on the slide expanded upon the recommendations in the lead article and include NSITE investigator papers on what genome sequencing can offer to universal newborn screening programs, single gene sequencing for newborn screening, commercial interest in sequencing the genomes of newborns and using newborn genome sequencing to advance our understanding of the natural history of genetic diseases. Now a few weeks ago we held the 11th in a series of genomic medicine meetings as organized by the Genomic Medicine Working Group of this Council. The Genomic Medicine 11 Meeting was held in conjunction with the 2018 AGBT Precision Health Meeting which annually brings together genomic researchers, healthcare professionals and the healthcare industry stakeholders to discuss the movement of genomics into clinical practice. Now Genomic Medicine 11 or as we refer to it as GM 11 builds on the success of the 10th Genomic Medicine Meeting which focused on research directions in pharmacogenomics implementation and led to this recent review in clinical pharmacology and therapeutics. Now the objectives of GM 11 were to summarize the current state of genomic medicine implementation research to identify obstacles in genomic medicine implementation and how best to overcome those obstacles and to define where implementation of genomic medicine should be in five to 10 years from now and also how to get us there. The meeting also aimed to inform genomic medicine aspects of NHGRI's ongoing strategic planning process. Key recommendations coming out of the meeting included establishing a systematic guideline development process similar to the Clinical Pharmacogenetics Implementation Consortium or CPIC for non-pharmacologic genomic medicine relevant genes also curating a registry of patients with genomic data to follow for outcomes developing a limited training program for a majority of common complex disorders for non-genetics clinicians and certifying them as genomic consultants and engaging employers who pay for the vast majority of non-government sponsored healthcare as key stakeholders. And Terri Minolio will discuss these recommendations further in her update on the Genomic Medicine Working Group which will take place later today. Now in April, NHGRI and the Eunice Kennedy Shriver National Institute of Child Health and Human Development or NICHD hosted a joint workshop actually in an adjacent building from where we are sitting entitled Genomic Medicine for Reproductive Prenatal and Neonatal Health. Attendees included leaders from diverse fields of study including researchers, medical providers, bioinformatician, ethicists, industry representatives, insurance providers, representatives from professional organizations, government stakeholders, and others. The following questions were considered at this workshop what current technologies are ready for implementation in reproductive, prenatal, and neonatal health, what are the ethical, legal, and social implications of genomic medicine implementation, and what are the challenges in implementing genomic medicine in reproductive, prenatal, and neonatal health. Attendees were enthusiastic about the joint workshop and several recommendations came out of the meeting. These included the desire to determine if reproductive, prenatal, and neonatal omics are good predictors of later health and disease, to address barriers in linking medical records to reproductive, prenatal, and neonatal health, and to increase collaborations to improve the implementation of new technologies and healthcare systems. The full set of recommendations and the meeting summary can be found on genome.gov and also linked to document 23. The NHGRI Computational Genomics and Data Science program supports research and development of data science methods, resources, and tools that maximize the integration of genomics data into biomedical research. In July, the program released two program announcements to increase the pool of investigator-initiated applications for a broad range of innovative research efforts in computational genomics, data science, statistics, and bioinformatics for basic and clinical genomic science. In particular, these funding opportunities are intended to support the research interests of the informatics and data science communities. The first due date for applications is November 16th of this year. Additionally, companion Small Business Innovation Research or SBIR and Small Business Technology Transfer or STTR funding opportunity announcements or FOAs are in development. And the NHGRI's Computational Genomics and Data Science program recently funded the formation of the analysis, visualization, and informatics lab space, otherwise known as ANVIL. Now, Anthony Philippakis of the Broad Institute and James Taylor of Johns Hopkins University will collaborate with 11 other partner institutions to establish ANVIL as a cloud-based infrastructure and software platform. This platform will support genomic data sets, phenotypes, and metadata from both NHGRI-funded programs as well as user-uploaded data. A shared analysis and computing environment based on the Broad Institute's FireCloud platform will also include popular informatics tools such as Bioconductor, Galaxy, and Jupter notebooks. ANVIL will also provide training and outreach to both biomedical data science experts and new users. Moving on, a notice of interest for applications to support the biennial ethical, legal, and social applications or LC Congress was released in July. The NHGRI periodically supports the LC Congress to bring hundreds of multidisciplinary LC researchers together to present their work and learn about other research in the field. The deadline for applications is November 12th. Now, a new request for applications or RFA for the Center for LC Resources and Analysis or CIRA has been published. The purpose of this Center is to provide LC researchers with an established platform to share the research tools and products related to genomics, serve as a resource that curates and this emphasizes LC research on key topics in the field and highlights new findings and provides access to these works as well as convening LC researchers for both small and large-scale transdisciplinary projects and meetings. The public webinar about this RFA was held earlier this month and updated FAQs have been posted on the LC website and the application deadline for this Center is November 8th of this year. In August, the President signed the John S. McCain National Defense Authorization Act that through this reauthorization addressed key aspects of the small business program. NIH will be working to implement these changes in fiscal year 2019. Provisions of notable interest to NHGRI grantees are as follows. The successful Direct to Phase II grants option was reauthorized which means Phase II applications without a prior Phase I grant will continue to be allowed. The technical assistance options and support for small businesses that many grantees have found useful will be expanded. And finally, congressionally mandated set-asides remain at their current levels 3.2% of the extramural research budget for SBIR grants and 0.45% for the STTR grants. Note that in fiscal year 2018 NHGRI invested $15 million in small business genomics commercialization efforts which was part of a significantly larger $1 billion of NIH's small business investment. The Genomic Innovator Award is a new NHGRI program that's designed to support early careers researchers to do highly innovative work on important problems in genomics. This award will take a people-based approach. By that I mean historically most NIH-funded awards such as the traditional R01 have been project-based. But recently NIH has been experimenting with R35 funding opportunities that flip that model and focus on individual researchers rather than specific projects. With this new program NHGRI is focusing on the unique population of genomicists who start their careers in consortia or other team science efforts. So to be eligible for this award applicants must have be early in their careers and have demonstrated the potential to make important contributions to the field of genomics. They must further have a history of being major participants in consortium or other group efforts and must propose work that falls within NHGRI priority areas. The annual receipt date for application will be October 30th starting this year. Now as we introduced in May my director's report is now including a section on NHGRI's extramural research highlights. This section includes papers nominated by NHGRI program directors that exemplify other exciting genomic research funded through NHGRI's investigator initiated awards. Matt Weirich and Lee Katyan and colleagues published a functional genomic study in nature genetics that examined transcription factor binding sites for multiple phenotypes. The viral transcription factor EVNA2 appears to bind low side that harbor risk variants associated with numerous autoimmune diseases indicating potential gene environment interactions of these genes and the Epstein-Barr virus infection. This work in part based on data from NHGRI funded resources including Cistron, ENCODE and the GWAS catalog as well as the NIH Common Fund resources GTECS and Roadmap Epigenomics. Ruth Johnson and colleagues published a paper in Bioinformatics entitled a Unifying Framework for Joint Trade Analysis under a non-infantesimal model. This paper describes how a large proportion of genomic risk regions identified by genome-wide association studies or GWAS are shared across multiple diseases and traits. The authors formulate a Bayesian generative model that relates the overlap between pairs of traits to GWAS summary statistical data and provide a flexible unifying framework to quantify the overlap called UNITY for unifying non-infantesimal trait analysis. And then in this nature oops in this nature communications perspective Nana by Garrison and colleagues discuss how indigenous communities remain a starkly underrepresented group in genomic and precision medicine research to foster research collaborations with these indigenous communities six principles and practical examples are proposed that aim to build trust increase inclusion and promote tribal oversight. And finally Ryan Lauer Aaron Quinlin and colleagues published this paper in Nature Methods entitled and I don't kid you Giggle a search engine for large-scale integrated genome analysis. Giggle functions as a Google search engine for genomic regions in a fashion that allows users to rapidly query rank and compare genome-wide assays from in lab experiments or large-scale data resources. Giggle extends the accessibility and utility of resources like in code and GTACs and roadmap epigenomics with exceedingly fast comparisons that facilitate data integration and hypothesis generation. Okay. Moving beyond NHGRI we'll go to NIH Common Fund and other trans-NIH efforts and we'll start with the NIH Common Fund's knockout mouse phenotyping project or COMP-2. This project will create and phenotype 3,000 strains of knockout mice using CRISPR technology between 2016 and 2021. COMP is on track to meet its goals for the fall of 2018. The program is part of a larger international mouse phenotyping consortium or IMPC. This year's annual COMP-2 meeting will be held in Rockville, Maryland on September 30th to October 2nd. The last day of the meeting will focus on COMP's two collaborations with various human disease gene discovery programs such as the trans-OMICS for precision medicine top med, Gabriella Miller-Kid's first and ClinGen. The discussion will focus on optimizing the utility of COMP in human and medical genetics. It's also notable that COMP-2 sites received a total of seven supplements for fiscal year 2018 from NHRI, from the NIH Common Fund and four other NIH institutes. The NIH Common Fund's Library of Integrative or Integrated Network-Based Cellular Signatures or LINX program is intended to create a network-based understanding of biology by cataloging changes in gene expression and other cellular processes. LINX uses computational tools to integrate the diverse information for the development of new biomarkers and therapeutics. Now, LINX data usage continues to grow yielding many publications and citations. The figure shown here represents the number of publications that have used LINX data. This excludes publications by members of the LINX consortium itself and currently totals over 2,400 citations. Outreach efforts continue to be a high priority for LINX In a recent community challenge, participants significantly improved query speed from the linear benchmark. In fact, one contestant from the community-designed program that exponentially sped up the compute time processing 500 queries nearly 100 times faster than the benchmark. The software has been tested for robustness and deployed on the LINX query portal. And finally, LINX investigators will hold an important outreach event in Boston on December 4th through 6th. Participants will learn execution of web and API-based queries and provide feedback to help improve user interfaces. Information about registering for this event will be available on the LINX website in the near future. The central goal of the NIH Common Funds Human Heredity and Health in Africa or H3Africa is to develop a sustainable and collaborative African genomics research enterprise. Entering its seventh year, the consortium now supports 48 projects across 34 African countries involving over 5,400 research participants to date. Samples for more than half of these participants are now deposited in an H3Africa biorepository. And the genomic data are with H3Bionet for eventual sharing across the European genome phenome archive. As of August, the H3Africa consortium had approximately 200 scientific publications. And as shown on the bottom right was also featured along with NHGRI intramural senior investigator Charles Rotimi in a recent issue of Newsweek magazine. Now last week, I personally attended the 12th H3Africa Consortium Meeting in Kigali, Rwanda which was held jointly with the 11th annual African Society of Human Genetics Meeting. The meeting featured a number of notable presentations including welcome remarks by Rwanda's Ministry of Health the photo on the left. Key topics covered during the meeting included the sustainability of genomics and human genetics in Africa especially beyond H3Africa support, translational genomics and training. The meeting was complemented with workshops on environmental health, on community engagement and on next generation DNA sequencing analysis. In addition to giving a keynote talk, I participated in a panel discussion about sustainability that's the photo on the right. And then Jen Troyer and I hosted a session where we collected input from the attendees about NHGRI's ongoing strategic planning process. And finally, there are three new H3Africa ELSI awards that have been made to investigators in the indicated countries expanding ELSI initiatives in biobanking, community engagement and ethical guidelines for genetics research. 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 those diseases and promote an integrated and collaborative community to investigate these difficult to diagnose conditions. The UDN is now starting its second phase of Common Fund support. Phase two will significantly expand the footprint of the UDN with five new clinical sites, a new metabolomics core and increased model organism capabilities. To apply to the UDN, simply access the UDN gateway by clicking on the apply button which appears on all of the UDN webpages. One can also find real-time research updates by following UDN on social media using the hashtag UDN Connect. HubMap is a new NIH Common Fund program. Its vision is to catalyze the development of an open global framework for comprehensively mapping the human body at a cellular resolution and its premise is that better insights and the principles governing organization function relationships will lead to better understanding the significance of inter-individual variability changes across the lifespan tissue engineering and the emergence of disease at the biomolecular level. Awards will soon be announced for tissue mapping centers which will generate high-resolution multi-scale maps of non-diseased human organs and systems also transformative technology development groups which will establish proof of principle and validation of the next generation of single-cell tools and also the HubMap integration visualization and engagement or HIVE which will manage the data generated by HubMap coordinate activities develop novel tools for visualizing, searching and modeling data and also build an atlas of tissue maps. A HubMap consortium kickoff meeting will be held in late November of this year. The NIH Common Fund is also launching yet another new program called Sematic Cell Genome Editing which will aim to develop quality tools to perform effective and safe genome editing in human patients. The program elements will include improved delivery systems and genome editors as well as in vitro and in vivo assay platforms to test safety and efficacy. The information and materials will constitute a genome editing toolkit that will be disseminated through a data coordination center. The first round application reviews are complete and awards are being made and meanwhile a kickoff meeting of the new grantees will be held on December 10th and 11th of this year. Moving beyond the Common Fund but staying within trans NIH initiatives the All of Us research program tends to build a national research cohort of one million or more participants reflecting the diversity of the United States. Program is creating partnerships with participants in order to advance precision medicine and to change healthcare for the benefit of all. As many of you are aware all of us officially launched this past May. As part of the launch the program started the All of Us journey a bus tour designed as an exhibition to travel throughout remote areas of the United States to increase community awareness about precision medicine and about the All of Us program. To date over 100,000 people have signed up to participate and over 50,000 have completed all the available protocol elements. In August All of Us launched its research hub website where visitors can get an overview of the plans for data access including tools to query the data. All of us aims to build a diverse community of researchers. Interested researchers should go to the research hub website and register to get updates including notifications about when the first versions of the data will become available. An important development is that Dr. Kelly Gabo has joined All of Us as the new chief medical and scientific officer. In this role Dr. Gabo will work with healthcare professionals researchers participants and national community-based organizations to lead the program's scientific agenda with a special focus on populations that have been historically underrepresented in research. She will also work with key stakeholders including participants NIH leadership and partners to guide protocol revisions and data collection processes. Dr. Gabo comes to All of Us from Johns Hopkins University where she is a professor of medicine and an expert in HIV health services research and clinical outcomes of persons with HIV. Moving then to NHGRI's Division of Policy Communications and Education I want to bring to your attention a new online resource on genome.gov that highlights synthetic biology. While this field is not specific to NHGRI there are important advances in synthetic biology garnering scientific and media attention. The purpose of this new website is to offer high-level overview of synthetic biology along with examples of its genomic applications and a synopsis of its ethical, social and legal considerations. Kara Palmer and Janine Mayosevich from NHGRI's Communications and Public Liaison Branch participated in NIH's first ever This Is NIH Social Media Takeover in August. During this event NHGRI assumed temporary editorial control of NIH's social media accounts during which we highlighted NHGRI's programs, staff, and genomics research breakthroughs. Social media continues to be an important vehicle to help increase awareness about our research programs and to reach broader and more diverse audiences. NHGRI's Education and Community Involvement Branch had a busy summer engaging in outreach activities with high school students, congressional staff, and the general public. For the first time, NHGRI's Policy and Program Analysis Branch and Education and Community Involvement Branch went to Capitol Hill together to participate in the Capitol Hill Maker Fair. At the fair, the two branches showcased hands-on activities such as strawberry DNA extraction and technologies such as nanopore DNA sequencing. They also highlighted bioinformatics tools to illustrate how genomic information is becoming more accessible and how genomics is becoming more important in the education, economic workforce development, and medical innovation sectors. In addition, the Education and Community Involvement Branch interacted and engaged with 380 students, parents, and community members through various public programs from mid-May through the month of August. This included our third year of introducing high school students from the Prince George's County Youth Career Connect Program to NHGRI and also to Genomics as a possible career path. In late July, NHGRI held its annual short course in Genomics. This year's course organized by the Education and Community Involvement Branch welcomed more than 20 faculty members teaching at middle schools, high schools, community colleges, and tribal colleges from places as far away as rural Arizona to as close as Montgomery County, Maryland. These educators spent four days at NIH hearing lectures and receiving teaching resources from leading NHGRI and NIH researchers, clinicians, and staff. They also discussed ways to incorporate genomics content into their courses and participated in tours of NIH facilities. Topics included bioinformatics, CRISPR-Cas9, bioethics, genomics and human disease, cancer genomics, and DNA sequencing technologies, among others. This year, a number of alumni returned to the course to build upon their positive experiences, to share knowledge, and to help form educator networks. For the past two years, staff from NHGRI's Education and Community Involvement Branch has been working in partnership with two tribal college faculty who attended our 2016, who attended our 2016 short course in genomics for educators to establish the tribally-driven and initiated Tribal Colleges Consortium on Genomics Training, or TCCGT. Now, TCCGT was established to increase the coordination between tribal colleges as well as with federal agencies and other institutions to expand training and research opportunities in genomics and to discuss how to incorporate genomics in the context of traditional tribal views. TCCGT has been well-received by tribal colleges and continues to grow and receive support. To build on this momentum, any share I hosted a two-day workshop in June at NIH with faculty and staff from Dine College, Northwest Indian College, Sitting Bull College, Dahona-Udham Community College, Turtle Mountain Community College, and United Tribes Technical College. The first day of the workshop offered a series of talks and discussions about the landscape of genomics. During the second day, participants worked in teams to develop potential pathway models for genomics education districts that could be implemented within the consortium. Plans are underway to begin piloting some of these initiatives that were developed during the workshop. And lastly, the Genome Unlocking Lives Code exhibition will make several more stops across North America as it continues its road show through 2018 and 2019. The exhibition just completed its day at the Rochester Art Center in Minnesota last week. I actually saw it there a couple of weeks ago. It is now traveling to Florida for a run at the Orange County History Museum in Orlando. Following its stay in Florida, the exhibition will travel to the McWayne Science Center in Birmingham, Alabama. Please continue to check the exhibition's website and follow it on social media for the most up-to-date program information. And lastly, just a few things I want to say about the Institute's intramural research program starting with this one. Max Munker and colleagues in the Medical Genetics Branch of our intramural research program are right now hosting the third International Summit in Human Genetics and Genomics. This summit is part of a five-year initiative that involves annual month-long workshops held at NIH. The summit is designed to help developing nations build expertise, infrastructure systems and technologies in genetics and genomics. The summit is sponsored by NHGRI by a collection of other institutes and centers, by the Foundation for the NIH, and by additional profit and non-profit partners. Each summit involves a month-long curriculum that involves courses and tailored training for the participants. The program is intended to train healthcare professionals and trainees from developing countries that are in their early-to-mid career stage. The 2018 summit has 26 participants from countries across the globe. Applications for the 2019 summit will be accepted in October and November of this year. An NHGRI's Intramural Research Program has been its usual productive self since the last time Council meeting was held. I'll just give you a few notable highlights. Pam Schwartzberg and colleagues developed a new mouse model of human immunodeficiency disease caused by mutations in the gene encoding PI3 kinase delta. The findings published in Nature Immunology have brought implications for people with immunodeficiencies and autoimmune conditions. Bill Paven and colleagues discovered a connection between genes that contribute to hair color and genes that control the body's immune system. This new mouse study published in PLOS Biology offers insights into why some people's hair goes gray in response to serious illness or chronic stress such as being an institute director, for example. Ben Berkman and colleagues discussed the ethics of using genealogy data to study crimes in an annual annals of internal medicine commentary published soon after the arrest of the suspected Golden State killer. And that brings me to the end. But before ending my direction report, I want to, as I always do, put in a plug and say anyone wishing to receive my monthly email update called the Genomics Landscape can simply go to NHGRI's website genome.gov and subscribe under email updates. And of course, finally, a personal thanks to the 50 to 60 NHGRI staff members who helped put together this 71 slide deck that I just reviewed as part of my director's report. As always, I don't do this alone. Far from doing it alone, it is absolutely a group effort. And we do it to try to convey as much information to you as possible through my director's report. An additional thanks to the communications group and the web team for making my director's report an electronic resource. And it's always a special thanks to the usual ringleader in preparing my director's report, Chris Wetterstrand, here. She's taking a selfie in my office suite with some of our local DNA decor. And just one last thing before I turn the microphone back over to Rudy, I do want to, and since I have the mic, I can keep it. I do want to put out a second special thanks to a number of people associated with preparing for this council meeting in this new conference room at this new building. These new digs, there's a lot of high tech stuff in this room but I just want to emphasize how dedicated the institute and our colleagues from other parts of NIH such as events management, how seriously we take these council meetings. There was an inordinate amount of logistical details to start to get everything set up for today. And it's because we take these meetings very seriously and we wanted everything to be perfect. And so I just want to give my own special thanks to members of our information technology team, our communications team, Rudy and others that work with them running around. There's like been multiple rehearsals in this meeting. Many of the extramural staff have come down and thought about little details to work out. So and people in our administrative staff as well, there was a lot of worry that went into the meeting. So far, everything's going well but I just wanted to give an extra thank you to all the people that worried about today because it really is a reflection how seriously we take these council meetings. Everybody wanted everything to be perfect and so far so good. But thanks to all of them and thanks to NIH events management for working with us since this is technically their room but it's also an important meeting and they realize how important this is to NHGRI. So thanks to all of them and with that I will conclude by director's report. Happy to take any questions otherwise if there's not any immediate questions I'll turn this over to Rudy. Anything immediately? Yeah, yeah. So for the genomic innovator you mentioned that you must have a history of being a major participant in consortia or other group efforts. So maybe you can tell a little bit more about what that means. At least I would be happy to. And while she's walking to a microphone I am quite sure one of the things she will tell you is we didn't want to be overly specific. We want the grant review process to help inform what we mean by that. So it's left to some interpretation but we just came out of this council recognize that there was a population of folks that really have embraced team science are valuable parts of the community that occasionally have sort of had difficulty because they were team oriented being able to be viewed as independent and so when they went out and tried to be independent might have been handicapped in some way and we wanted we were hoping to help facilitate some of those individuals. Precise definition was to be interpreted as part of the review process. Add to that Lisa. Okay well I don't think I have much to add to that. We're being very open about this. We don't have any cut and dried boxes except there was like somebody who was a center director and of the two centers and we thought that didn't really sound like somebody who's embedded in the middle of it. So we're really being very open consortia. There's some people who work for like core facilities and they work with a lot of groups. Some people have worked with several consortia groups others have been single ones. Some have been in SEGs part of large groups. So there's a lot of possibilities. And Lisa's a fair to say you are sort of implied it. I mean if when in doubt contact Lisa to you know to have a conversation. They all have. Yeah they have. That's great. No that's what we want. You know and I'm sure after a round or two of these we'll have a much better idea of what seems right and what doesn't. So we want the dialogue so if in doubt ask. Other questions. I think we're in good shape.