Elise Feingold: Okay.
Great.
Thank you.
I also want to extend my welcome to everyone.
We are really excited to have you here, have our NHGRI colleagues as well as NIH colleagues
here and people who are watching on webcast.
We are very excited about this workshop and looking forward to the discussions over the
next day and half.
Eric actually covered a lot of the points that I wanted to make and so I hope we can
go through this fairly quickly and catch up a little bit on time.
So I want to go over a little bit more about the purpose of the workshop and background
about ENCODE and a little bit more detail about the planning process for the future.
So as Eric mentioned, ENCODE is ending, this current phase in 2016, and so we really wanted
to bring together the community to get input on what NHGRI should support in the area of
functional genomics and just build on the success of ENCODE.
And so I think Eric made this point already, but I think it’s worthwhile repeating, is
that functional genomics really is central to realizing NHGRI’s goals.
We know that noncoding DNA is important for disease and gene regulation.
We know that about 90 percent of GWAS findings lie outside of protein-coding regions.
We know that non-coding DNA variants can cause human diseases and alter human traits and
about 80 percent of recent adaptation signatures lie outside of protein-coding regions.
So we feel that comprehensive functional information about the human genome is really critically
needed for the interpretation of genomes, understanding genetic variation and applying
genomics to the clinic.
A little bit more background about ENCODE.
That workshop was July of 2002 actually, which was about a year before we had the strategic
plan that came out with the completion of the human genome sequence.
So the goal is to compile a comprehensive encyclopedia of sequence features in the human
genome and in the genomes of model organisms and to make the resource freely available
to the community to enhance our understanding of the regulation of gene expression and the
genetic phases of disease.
This slide shows the timeline for ENCODE.
As Eric mentioned we started with a pilot project to focus on 1 percent of the human
genome in 2003 and at the same time, we initiated the first of a series of technology development
efforts.
We felt that technology development was really a critical part of what we needed in order
to meet the goals of ENCODE.
Then based on the success of the pilot project, back in 2007 we launched the first production
phase, and that was -- went from 1 percent to 100 percent of the genome focused in human
and then at the same time we started the modENCODE project which was focused on creating a resource
of functional elements in C. elegans and melanogaster genomes and those ran concurrent from 2007
to 2012.
And then in 2009 with some money from the economic stimulus, we were able to launch
a modest effort in mouse ENCODE that also went through 2012.
So as we were nearing the completion of these projects in 2012, we recognized that we still
had a long way to go in completing the catalogues and so we initiated the ENCODE Phase III which
we are in right now.
We started in 2012, ending in 2016.
That was focused specifically on human and on mouse and then we also funded a number
of computational analysis awards because we felt that we really needed to bring a lot
of expertise to the question of how we are going to be able to interpret all of this
data and understand it.
And also in 2012, we launched the fourth initiative and technology development.
Just very brief overview of the ENCODE data slides.
I think Mike Snyder is going to go into this maybe in a little bit more detail.
So this is a cartoon that shows ENCODE implies a series of hyper technologies that are primarily
sequenced based to measure a number of different biochemical signatures in the genome including
transcription, DNA methylation, histone modifications, DNA hypersensitivity and the data that is
coming from those assays are used to map genes and transcripts and identify candidate promotors
and long range regulatory elements such as enhancers.
This slide outlines the structure -- current structure of ENCODE, which is fairly heavily
managed consortium.
We have a number of data production groups and they deposit their data into the data
coordination center which does quality evaluation, uniform processing, it stores the data and
makes it available to the community.
The data is then taken up by the analysis-working group, which is supported by a data analysis
center, and they generate gene models, chromatin states and identify key elements that really
comprise this encyclopedia.
A computational analysis groups work together with the analysis working group and the technology
development groups are generating or exploring obtaining information about how to find new
functional elements, how to validate them and how to analyze the data.
So I just want to highlight a couple of the features of consortium, as Eric said, this
is how we run this program and some other program.
This is one model; there are a number of them.
The consortium is really highly collaborative and synergistic effort benefits by a lot of
exchange of information and ideas within the group.
There is a mix of investigator-initiated and top-down directed projects.
As I mentioned, there is focus management coordination, for example, the data production
groups have quantitative milestones and we bug people for quarterly reports on progress
towards those milestones.
This generation of high quality data, I think Mike is going to touch on this a little more.
They use cost-effective and high-throughput methods, and I think what’s key here is
really being able to take advantage of the economies of scale.
There is a focus on resource generation for the community and we work to actually balance
the needs of the individual researchers, allowing them to publish on their own data but also
getting the data out very rapidly to the community and we’ve been developing data standards
and common data formats and using common cell types in some cases to facilitate data integration
and analysis and this also provides transparency about data, experiments and data quality.
I just want to give a few highlights of ENCODE accomplishments, again Mike is going to go
into this in more detail, but I thought it was important to recognize a few of these
at a higher level.
There is rapid release of thousands of experiments.
These are, again as I mentioned, high quality and well documented.
They are uniformly processed and these processing pipelines are available on the cloud.
We developed and disseminated analysis tools and actually, the data coordination center
has been taking the lead in data interoperability and developing working with other projects
to create -- to work with common metadata standards so that the data from different
projects can be understood well from one to the other.
ENCODE has updated informed consent language for open access to genomic data and we are
working to obtain samples with this consent so that data is out and not put behind [inaudible]
gap or so in picking at the raw data.
We have been in a series of publications and we are most gratified to see that the data
has been used by the research community in over 700 publications, which is probably an
underestimate ‘cause it’s hard for us to track all this.
And these publications include disease studies that help identify causal variants.
So as Eric mentioned, ENCODE is not the only project that we support in functional genomics.
NHGRI also supports Genomics of Gene Regulation and FunVar.
The NIH Common Fund supports epigenomics as well as the GTEx and KOMP projects, the management
of GTEx and KOMP also are housed at NHGRI, and there are international projects such
as the International Human Epigenomics Consortium.
Mike Pazin and Mike Snyder and Dan Gilchrist are going to tell you more about these a little
bit later today.
So I think we have been through this; I will just briefly mention the objectives of the
workshop are to discuss the scientific questions and opportunities for better understanding
genomic function and applying that knowledge to basic biological questions and disease
through large-scale genomic efforts and considering what projects that NHGRI should support in
this area.
When we have these discussions, we want you to consider a couple of points.
The main areas of discussion are going to be on continued data generation, how NHGRI
can enable basic biology and disease studies for really the rest of the world to be conducting
and underlying all of this will be discussions about technology development.
We are looking for bold new ideas that NHGRI can catalyze.
Just a word of caution, we are looking for fairly general advice, at high level we don’t
want very detailed advice so we don’t want to put anybody in conflict for future funding
opportunities and again think about what is appropriate for NHGRI versus other funding
institutes and agencies.
As Eric mentioned, NHGRI has a long history of supporting resource generation and dissemination,
technology development, implementation of new genomics technologies and approaches.
We do support a lot of research consortia when a high level of coordination and staff
involvement is appropriate but as Eric mentioned we have various models for this, which have
varying degrees of coordination and management.
And we also do support investigator-initiated research as well as training and SBIRs.
I want to give a brief overview of the framework of the agenda to get everybody oriented.
We are going to start with some introductory talks to set the stage.
First talk from Ewan Birney about defining the scientific challenges, then we are going
to hear about the series of related projects.
Then we are going to hear two proposals for future directions.
One is the current ENCODE PI’s vision for functional genomics as well as recommendations
from the sequencing workshop that Eric mentioned, specifically integrating genomic variant discovery
with genome function.
These are really just ideas that the community has already put forward that really are just
starting points for discussion today and tomorrow.
Then we have organized really the rest of the agenda focus on these three topics.
The first is on identifying and characterizing functional elements.
The second is on using genomic assays of function to interpret the role of genetic variants
in disease and the third is on using genomic assays of function to study basic biological
questions.
We do recognize that there is going to be some overlap in these discussions and that’s
fine, we want to see where these intersections are and we also want to see what is unique
for each of these topics.
You should have gotten a handout for discussion questions for topics one through three.
If we don’t, there should be more at the registration desk.
I am not going to go into these but we have established questions that are going to be
used by the moderators to help frame this discussion.
And then tomorrow afternoon we are going to have overall discussion on looking at cross
cutting ideas, what are all the different ideas that people have for programs, what
their priorities are and what might the balance of activities be.
So the next steps, we are in the middle of the planning process right now.
We have in this planning workshop and then as Eric mentioned we are going to be taking
one or more concept clearances to be reviewed at the May advisory council and then depending
upon the outcome of that discussion we will have potential funding opportunities to be
released this coming summer, 2015, with review and funding in 2016.
And we do actually have four council members here.
Eric Boerwinkle, Carol Bult, Joe Ecker and Jason Drury [spelled phonetically] and so
they will be able to represent these discussions at the council meeting as well.
Okay, I think Eric already went through this so with the organizing committee, he has already
thanked them, I will also add my thanks as well as thanks to Saundra Bromberg from Capitol
Consulting Corporation, the ENCODE consortium of course.
This is a picture from last year’s consortium meeting, there was about 180 people and this
Saturday we are going to have this year’s meeting and I will tell you it won’t look
quite this nice.
It will be out on Long Island and we’re hoping there is not going to be too much snow
on the ground.
And Eric mentioned that the ENCODE external consultants panel, Eric Boerwinkle, David
Kingsley, Dana Pe’er, Paul Sternberg and Olga Troyanskaya and everyone except, I believe,
David is going to be here at the workshop.
And then final thanks to NHGRI staff, my colleagues working in ENCODE -- Mike Pazin and Dan Gilchrist,
Adam Felsenfeld from the large scale sequencing program and division director Jeff Schloss
have really been very helpful in organizing this workshop, as well as our program analysts
Hannah Naughton and a special shout out to Julie Coursen who has taken the lead in organizing
this workshop for us.
Finally, I hate hinting on such a mundane note but we do have a number of housekeeping
items to mention.
Reminder we are webcasting this, so please use the mics which Eric reminded us of.
You should have received an invitation to join Googledoc or have access to the Googledoc
for meeting notes.
This is meant primarily for the organizing committee and NHGRI but everyone
-- all the participants can have read and comment access to this document.
The Capitol Consulting Corporation staff is on site, if you have any questions.
We will be receiving boxed dinners delivered late this afternoon.
If you haven’t ordered one, during the coffee break, you can go upstairs and there is a
café open and you can pick up some snacks for later.
We will have a shuttle today at the end of the session going back to the hotel at 9:00
p.m. and then picking you up again starting as early tomorrow morning at 7 a.m. in order
to get you through security and get coffee and some breakfast.
You should order your transportation to the airport either through the hotel or see the
Capitol Consulting Corporation staff before lunchtime tomorrow to sign up.
And please don’t forget to send your reimbursement vouchers to the Capitol Consulting by the
end of March.
So on that note, I guess, Mike, do I have time for if there are any questions?
Anyone have any questions?
If not, I think I’m probably just going to turn it over to Ewan who is going to give
the next talk so we can get back on schedule.
So it is really a pleasure to invite Ewan back to the ENCODE discussion and we have
asked him to give a talk on defining the scientific questions really setting the stage for the
rest of the workshop.
Ewan Birney: Okay.
Elise Feingold: Thank you.
[end of transcript]