 Good morning afternoon. I just want to start off by thanking the organizers for inviting me here today My name is Stephanie Morris and I'm a program director at the National Human Genome Research Institute Within the National Institutes of Health. I'm here representing the ENCO program team at NHGRI Where today I'll provide a brief overview of ENCO, the encyclopedia of DNA elements I'll tell you a bit about how it started the goals where it's been and where it is now So this program has been in place for over the last 17 years It was initiated after completion of the human genome project in 2003 There are two overarching goals The first of which is the cataloging of all of the functional elements and the human genome and the genome of model organisms So this includes mouse worm and fly When we say functional elements, what we mean are protein coding and non-coding regulatory elements That is genes and regulatory regions The second goal is to make this catalog and other resources generated by the program really available to the research community To enable enhanced understanding of gene expression and how it is regulated and also to enhance understanding about the genetic basis of disease So these goals came about because at the time of the completion of the human genome project It was known that non-coding DNA was important for genome function It was shown to be important for disease and gene regulation Many of these elements regulate gene expression and are only active in specific cells and tissues Also, the majority of common disease associations lie outside of protein coding regions This leads to a need to understand how these elements function to interpret the role of genetic variants So we have an understanding of the genetic code This project ENCODE aimed to learn and understand and regulatory code So what I have here is a slide that's really emphasizing the second ENCODE goal Of the program which is to serve as a community resource And the ways in which we're doing this is by putting an emphasis on rapid pre-publication Data release so all data producers available for unrestricted use by the research community immediately upon release External users can freely download analyze and publish results based on ENCODE data We have a dedicated portal where these data can be accessed And what we do is request that data be cited promotion of open access sharing of data Software tools and data analysis pipelines is also An important component of this being a community resource So to maximize this all data are shared in databases without controlled access Human biological samples are consented for unrestricted data sharing Um through the process of creating the catalog and the analysis of data generated consortium Investigators have developed common data reporting formats data standards And analytical tools that can be adopted and used by the broader research community An important important analysis that the consortium also continues to share the information through publications And this is resulting from the data produced and analyses And this is leading to independent publications So much of this is actually documented on the various websites from consortium members as well as ENCODE portal And this is information about these generated data analyses and tools So I want to get a little bit into the ENCODE timeline And wanted to mention that really there are three components to this project And that is data generation analysis and the development of this data repository As started with at the start of this talk ENCODE was started in 2003 and it started as a pilot with the focus on mapping 1% of the human genome And this was 2003 to 2007 This resulted in a second phase where this second phase transitioned into full scale data production It also was an introduction to the development of a data coordinating center responsible for tracking, storing and displaying these data And the data analysis center that's responsible for integrative analyses We also saw the introduction in phase two of mod ENCODE and mouse ENCODE So this is looking at the genomes of model organisms in this case flyworm and mouse We see as we move into phase three more of a focus on human and mouse projects And we see the funding of the first round of computational analysis projects Where these projects were being tasked with computational analysis methods To applying these to the data being generated by the consortium We also see during the first three phases of ENCODE that there have been four rounds of technology development Awards that were funded We see a lot of these activities continue in other NHGRI programs and efforts Such as the technology development program and do investigative initiative projects funded outside of ENCODE So examples of technology development Can be seen for chromatin accessibility Which went from DNA seek to fair seek and now we're seeing a lot of attack seek We've also seen changes in chromatin IP technologies So right now we're currently in the fourth phase of this program which started in 2017 Where activities and data production and computational analyses continue and we started a new component And functional characterization of ENCODE predicted candidate functional elements So just a little bit about how this fourth phase is organized There are 24 awards that are spread across five components And so we actually have eight centers focused on functional element mapping And these centers employ high throughput and some lower throughput genome wide experimental assays That are being used to map biochemical genomic features associated with functional elements You see that these funded centers are Where they can conducting experiments on common sets of biological samples And in this phase the focus is on mouse and human genomes with an expansion in the types of biological samples Including the potential to add those associated with human disease We also have eight functional element characterization centers Where they are developing and applying generalizable approaches to characterize the role of candidate functional elements in specific biological contexts So are the learning best approaches that will enable better understanding of the ENCODE catalog They are also reserving part of their experimental capacity to test a common set of elements And that allows for a comparison across Approaches so we'll see things like various reporter assays and genome editing within these centers We also have our computational analysis projects and in this round there are six of them Where they are developing and applying these new computational methods to ENCODE data to improve and interpret the catalogs of candidate functional elements And then we have the combined efforts of the data coordinating center And the data analysis center in the ENCODE data coordination and analysis center Where we have again the DCC is collecting housing and organizing and sharing ENCODE metadata and data through the ENCODE portal And then we have the DAC that provides computational expertise and performs integrative analysis of ENCODE data And is able to present enable and enable search of the registry of candidates to regulatory elements by a screen So an important to also point out is that the DCC and DAC are Actually taking in community data and they're able to handle that and enable sharing with the the public So for example, we have hosting of data from other programs such as genomics of gene regulation mod ENCODE and modern So this is a map of the current awardees just to give you a sense of where all of these Projects and centers are doing their research. They are located across the u.s. And some of them have Foreign institutions involved with their awards Also want to point out that we have projects that participate as affiliate members of the consortium Where they have opportunities to participate in the analysis working group as well as other working groups and in consortium activities So moving a little bit into the ENCODE assays with a focus on generation and analyses So ENCODE has produced and continues to produce data from a broad range of high and lower throughput Biochemical assays and methods I want to point out here with the red asterix. These are active ENCODE assays or methods But picture here are a variety of methods and approaches that have been used over the past 17 years The main approach being taken by ENCODE is that different biochemical features and combination of these features are associated with specific Genomic functions. So these can be mapped using a variety of genomic assays The mapping allows for the influence of the location of different elements like promoters enhancers and genes So we see here that we have approaches for looking at long-range interactions between chromatin regions So for example, high C and chia pet assays that are looking at chromatin accessibility As well as approaches for assaying his some modifications and transcription factor binding We have to use of computational predictions of genes and their relationship to regulatory elements And then we also have approaches like RNA seek and clip seek that are being used to look at transcription and the binding of proteins to RNA So for ENCODE all of this is being brought together and the encyclopedia which includes raw and processed data From all of the different assays and elements being called from the integrated data So these raw data are processed through uniform processing pipelines and called elements make up this registry of candidate regulatory elements So the ENCODE portal allows you to search the metadata for ENCODE experiments and provides access to over 16 000 data sets So this includes data from all three phases and the current phase of the program As well as data from other programs We also have this tool screen as mentioned and you'll hear more about the portal and screen and other talks throughout this meeting But for screen and it lets you search genomic regions and tells you what annotations are found from thousands of experiments Performed through the ENCODE program and also provides tools for visualization So there are a couple of really important points about ENCODE's approach to these assays that are important to point out There's a strong emphasis on rigor and reproducibility as well as transparency So under rigor and reproducibility, I want to point out There's a strong focus on the use of standardized protocols for assay experiments and data analyses The use of validated reagents and the validation of reagents As well as having quality metrics in place for the various data types to enhance rigor and enable reproducibility And then as mentioned, there are uniform data processing Pipelines and this is really especially important when the same data types are coming from different groups And then last but not least Some importance to structuring of data and metadata that enable the use of these data and downstream computational analyses So by structuring these data and metadata enable search and retrieval You can find out more about this on the portal under materials and methods So we have this last section here about ENCODE use cases and really this is just about how ENCODE is being used by the community And one thing to point out is really One way that the community can use this information is not only to report the ENCODE portal, but also through publications So what I want to point out here is that most recently the ENCODE phase three Um consortium members published a collection of papers and this was actually in the july 3th issue of nature This features 14 publications in nature and other major journals This is a way to share what the program has been generating and also provide information for others to use in their research studies These papers actually contribute to over 500 ENCODE consortium publications produced to date This particular package features a main paper that highlights the expansion of ENCODE's experimental catalog so this is used to identify cis regulatory elements and The creation of a comprehensive registry of these elements as mentioned during phase three recent introduction of screen And this is again a user friendly way to navigate the extensive catalog So you can see a paper about that as well The consortium also published a perspective of ENCODE Where authors took a closer look at the history of the project and its growth during The third phase of the program and really that opportunity to reflect on its impact in future directions We also find within this package additional publications that span various topics of human and mouse gene expression regulation Every genetics disease and software tools So this is really to point out that there's a lot of ENCODE data being shared by the portal And with the broader community through publications and that ENCODE data are widely used So we know this through the number of community papers that are using ENCODE data The table here on the left hand side is a papers published over time We have a southern point of august 2018 But as you just saw we have several papers coming out And I'm sure we'll have updates soon about papers being generated by the community So so far NSGI has identified more than 2200 community publications And this is shown by this red orange curve And these are from groups without ENCODE funding but who use ENCODE data for their published work ENCODE consortium members have produced more than 500 publications And that's going actually close to a thousand that's shown by this white curve And this is since the program started Further to this ENCODE has been used across a number of human disease categories Attesting to the translational value of the resource So I'll briefly mention here how the community is using ENCODE and this really falls into four different categories This includes technical products that may have various applications to your projects And this is these are products that have been Generated by ENCODE and are being used by other programs like gene code That's a resource that is focused on annotating genes in the mouse and the human genome We also have various approaches so protocols that are being used for carrying out assays and analyses In various methods used for analyses We also have Use cases that fall in the category of methods development and validation So these are experimental and computational New experimental methods being developed by members of the consortium and the broader community for generating data Similar to ENCODE and new computational methods for analyzing data types used by ENCODE and others And then we have this last category here Related to disease association and gene regulation studies So ENCODE is providing information on genes and regulatory elements that can be overly or used in conjunction with other studies To identify causal variants or enable you to learn more about the mechanism of your target gene adventures So basically what we're seeing is that this scientific community continues to utilize ENCODE data in new and innovative ways To better understand the human genome in its role in health and disease So i'll stop there And sort of end by thinking the ENCODE consortium and the NHGRI ENCODE team Really the consortium and NHGRI engage in a variety of outreach To the community at scientific meetings workshops and user meetings like this I do want to point out if you want to learn more and you can go to the portal Here's the link here ENCODE project.org Or you can go to ENCODE site on genome.gov And then there are opportunities to follow and learn more about ENCODE resources and happenings to facebook and twitter And with that i'll thank you for your time and ask if there are any questions