 Okay. Thanks, Mike, for that introduction to the series of concepts that we're going to be now discussing. I'd like to say that I'm presenting this on behalf of not only myself, but Mike and Dan, and I want to acknowledge a significant advice and input that we received from Adam Felsenfeld and Josh Schloss. Okay, so I'd like to give now just a real brief outline for my presentation. I'm going to review the timeline for these initiatives, discuss the overall goals, really pull out what we think is new from what's been currently done under ENCODE, then briefly describe each of the concepts, identify some opportunities we think there are for co-funding, and then describe the overall budget, and then after that I'm going to go back and just counsel can discuss and vote on each individual concept. Okay, so this is the timeline for the initiatives. As Mike mentioned, the current phase of ENCODE was funded in 2016, I'm sorry, 2012, and funding will be ending in July of 2016. We had the planning workshop in that Mike just described in March of this year. We're presenting the concept clearances to this council in May of this year. If these concepts are approved, we will be releasing the funding opportunities at the end of the summer in August of this year with the receipt date November signed to review the next winter probably in February or early March, and then next May we'll be bringing these applications back to to council for review along with the funding plan and then issuing awards in July of 2016. Okay, so based on the workshop recommendations that Mike just reviewed, we developed a series of goals for future initiatives. These include expanding the catalog of functional elements in human and mouse genomes, but moving now also beyond cataloging to understanding the functional walls of genomic elements in specific biological contexts. We want to develop strategies to apply these studies to disease. We want to increase the number of scientists from the research community that's participating to contributing to this resource. We want to develop analytical tools to enhance state of utility and continue to make the data tools, analyses, and assemble the psychopedia really available to the research community. And so in order to accomplish these goals, we are proposing four initiatives. The first is functional element mapping centers. The second is functional element characterization centers. There are computational analysis research projects. And the fourth is the encode data coordination and analysis center or finally known as the EdCAP. I'd like to highlight a few features of these initiatives. What really is, you think, is different than what is currently being done under encode. The first is functional characterization at scale. This would be, of course, under the characterization initiative. The second is direct application of functional genomics assays to disease studies. This would be both in the mapping and the characterization centers and significantly increase community participation through the mapping centers, the characterization centers, and the data submission to the EdCAP. This is the proposed organization of these initiatives with the green components being the new activities. The data production activities will take place in the mapping centers and the characterization centers in part with using samples that are contributed by the community. The data will be submitted to the encode data coordination and analysis center where it will be processed, housed, and displayed and made available to the research community and also analyzed to create the encyclopedia of functional candidate functional elements. We'll also be receiving community data to the EdCAP that can contribute to the encyclopedia. As before, we want to support computational analysis to contribute to both the analyses and directly to the encyclopedia. Now I'm going to describe in more detail the first of the four initiatives. The first is functional element mapping centers. The purpose is to expand the catalog of functional elements in the human and mouse genome. And this will be done by applying high throughput assays to map biochemical activities that are highly associated with specific functional elements and then expand its cell space that will include disease studies. And the idea is to support both technologies that are currently being used in encode as well as new technologies. For funding, we want to use a cooperative agreement U54 mechanism that we are currently using in encode to fund between six and eight centers for a total level of $20 million per year and total costs for four years. And the idea is to fund these centers, groups will be working closely together to form a research consortium as is the current model, currently being done in encode. Okay, so there are a couple of new features for these functional element mapping centers that I want to highlight. As we said, we want to broaden the community participation by obtaining unique biological samples from experts. And these may be as Mike has referred to these unbiased data collection for samples that are just not currently in the in the catalog. These may be a biological focus such as on the differentiation pathway, or they may be of disease interests. We are proposing to devote approximately 25% of the mapping efforts to disease samples. These are to disease studies. These can actually be samples from unaffected as well as affected individuals. Both will be contributing to the catalog. And we hope that we can learn something by by examining the differences between the unaffected and affected tissues, learn something about disease, and more broadly by studying a number of diseases, learn to how to develop a strategy that we can study disease using these molecular genomic assays more broadly in the future. We want to develop a scientific basis for bounding the experimental space. If you think about what we say we want to make a comprehensive, complete catalog, well thinking about every different puzzle cell type under every different environmental condition is really just unboundable. And so we want to through these centers, run experiments to try to bound it to try to identify really what are the most useful samples that we can use to do for very deep interrogation. We want to use only use samples that are consented for open access data release as Mike mentioned a little earlier. We are currently doing that. We've piloted that in the current phase of encode successfully. We believe that this will really make the resource much more more useful to the research community. We plan to have a limited focus on mouse due to the limitation in budget that we have and we are proposing approximately 10% of that effort being devoted to mouse and focused on adult tissues. We are currently in this basement code focusing largely on developmental on time course and so this we believe will nicely compliment that we believe this data will be helpful in annotating and understanding human genome. And then finally we feel we need to have flexibility in the pipeline. We may have some technologies that are not well tested and we may want to focus those initially on a subset of samples that are already well studied in encode and then if their feasibility of use and high throughput has been demonstrated then we might scale that up to many more tissues. We may want to bring in new technologies over time and we want to also be able to take advantage of new opportunities that are brought in by collaborators. Okay, so the second initiative is functional characterization centers. This is a completely new activity and the purpose is to enhance the catalog of functional elements by characterizing and validating a set of elements both in mouse and human. We're hoping to obtain an understanding of the utility and the generalizability of these functional characterization approaches. And we we would like to by comparing the different out methods, figure out the general strategy that we can recommend to the community for further study and also think of really important is to begin to develop ways in which we can better predict function. Under scope and objectives, we plan to support multiple approaches to test candidate elements in specifically biological context to validate and characterize functional elements. You can think about functional characterization. It's very broad. They're very different scales. You can think about function on molecular level or organismal level. Of course, biological function is very context dependent. So you may need to study it on different conditions. And then of course, there are a number of different function elements. So we do expect that we will need to be supporting multiple as multiple approaches. For funding, we want to support these as you will once again, using the cooperative agreement mechanism with feel we need to support a critical mass of these centers who are proposing between seven and 10 centers. Again, these will groups will work closely together. They will also interact with groups from the mapping centers as part of the consortium. And we are proposing $5.9 million in total costs per year for four years. So some of the key features of these functional characterization centers, applicants can select the cell system or biological context for in depth studies. Not list on the slide is of course, they will can can choose which functional elements they can be studying. We're going to specifically encourage studies of specific diseases using relevant cell sources. And similar to what I said about mapping centers, these can be done in samples that are highly relevant to a particular disease, but it can be an unaffected as well as affected. And by comparing them, we may be able to see how different functional elements operate under normal and disease conditions and also hope to develop a strategy for applying these assays to disease in the long run. Any group can propose to do multiple assays. And you can imagine that that groups may propose to study many functional elements using high throughput methods such as massively parallel reporter assays. They may want to study a smaller number of elements using lower throughput methods that may provide more physiological context such as in transgenic animals. The assays can be conducted in well justified model organisms, not just in mouse. They could do other model organisms such as zebra fish or whatever is well justified. They need to focus on either human or mouse function elements. We're asking that each groups devote 25% of their own effort to elements that are being studied by all so that we have some opportunity to be able to compare the different strategies and approaches that people are using on the same set of function elements to the extent that that's practical. And then again, we're looking only for use of samples consented for open access data release again to enhance the utility of those resources. The third initiative is for computational analysis. And the purpose of this is to maximize the utility of encode and related functional genomics resources by bringing in additional computational expertise to analyze encode data. This is another way we're trying to expand the participation for the research community. And so we're seeking here investigator initiated projects to develop and apply analytical and statistical tools to use and improve the resources for funding. We're looking for the cooperative agreement mechanism to fund approximately six projects at $3 million in total cost per year for four years. And we feel that again, we need a critical mass of these and we have benefited by the cooperative agreement mechanism currently to have groups working together and interacting and really understanding the encode data in depth. Imagine a number of different activities. Some are suggested here, which would include developing new methods to improve on the analysis, the visualization and interpretation of encode data, also by combining encode data with related functional genomics data from other projects to derive new biological insights. And using encode data to improve on the analysis of disease mapping studies to identify causal variants. Okay, and then the final initiative is the encode data coordination analysis center, ACAC. The idea is to support a center that can provide community access to encode data and resources, not only what will be conducted under this phase, but also what has previously been produced for encode. We also want to support the analysis of encode data necessary to create and make available a high quality encyclopedia for the community. We want to also support the the center to organize and facilitate consortium activities. And so what we plan to do here is to support a data coordination center and a data analysis center separately because we believe that there's specific expertise that's different for each group. So we fund them separately under this initiative, but we expect them to work very closely together and to really come together and function as a single entity. And this is model of what the current funding situation is for encode. In this initiative we want to greatly expand the activities for the DCC I'll describe in a moment over what is currently funded and the DAC activities will be more tightly focused on creating and validating the encyclopedia and a little less focused on integrated analyses. For funding we again want the cooperative remit U54 research resource mechanism again to funding two centers one data coordination center one data analysis center at seven and a half million dollars total cost per year and this is unlike the others which for four years this is for five years so we're proposing one year beyond the data production to help final final finalize all the data and have closed out activities. And related to that we're seeking additional 2.6 million dollars in FY 16 for the existing data coordination center to close out current encode activities and this is approximately 75 percent of their their current level of funding. So we're expecting that these two groups will work very closely together but based on the needs and the expertise will each group will have the lead in particular activities and I'm now just going to run through these I'm going to go these in a bit of detail because it's not always obvious what these what these groups are doing. The DCC will lead activities such as they will develop how to maintain databases to track store and provide access to data metadata and computational tools they will develop maintain and update data processing pipelines will maintain and enhance the portal to ensure easy access to the data and resources they will provide the to the community access to data in state-of-the-art browser visualization formats they will track and report on data submissions one of their new activities highlighted here in yellow is to import data from outside investigators and projects developing the needed infrastructure and methodology we expect that this will actually be a significant amount of work having to work individually with different groups they'll have to develop standards you know what is the minimum data quality etc to maintain the high quality resource and then another new activity is to serve as a data coordinating center and this would be to facilitate communication and coordination organize and support annual meetings and working groups and to support outreach activities to promote broad use of data analysis and tools and except for the outreach activities encode has not had this support previously unlike a lot of several other large projects that an HGRI supports and we feel this would be very helpful to have okay in terms of the DAC-led activities the DAC will specify and update data processing pipelines they will provide leadership and computational expertise analyze data for several different activities one is to update and refine the encyclopedia a new activity would be to develop the scientific strategy to bound the cell space to be deeply interrogated that I refer to under initiative one another new activity would be to expand the lexicon of functional elements beyond basic categories of promoter enhancer and insulator and we think the group feels very constrained by having such little few categories when you're thinking about function you know that it's more complex than that and then also to update existing and develop new data quality metrics and standards for all data types then finally a new another new activities we would like to the DAC to reserve small funds to be able to bring in additional expertise to conduct short-term specialized analyses needed to maximize the quality and the utility of the resource okay those are the four initiatives just want to point out a couple places where we seek opportunity for co-funding we plan to work with our colleagues and other institutes to seek support for projects that are focused on specific diseases or biology of interest to these other institutes we can imagine either whole or partial funding of projects especially for under the functional characterization initiative we could see supplemental funding for mapping samples that are mapping of samples that are particular interest to an institute particularly in the mapping centers and opportunity for supplemental funding to support submission of existing or planned data there's being generated under other projects that would go directly to the EdCAC okay this is a summary of the budget request we are looking for flat funding over four years for each of these four initiatives with the exception I just went over for the EdCAC of a fifth year funding to close out activities as well as an extension one year extension of the current DCC this is for a total of thirty six point four million dollars a year and this level of support is actually equivalent to the level that encode received in FY 12 the first year that this initiative that the current phase and encode was funded due to budget constraints however much of that funding was actually just for one year and so we've had to take significant reductions in the out years and so for the latest FY 14 is that we have the latest budget information this request represents approximately 21 percent increase of a what encode currently really has okay are there any immediate questions before we go back to discuss each of the individual initiatives yes so okay and I'm going to heavily rely on my colleagues here to help answer these questions so Howard