Teri Manolio: All right.
So I was tasked with kind of reviewing the things that we've been doing in these meetings
and at NHGRI in genomic medicine for the past year and a half, two years or so, just to
kind of give a context for where we are and where we're going, so we'll do that.
And just to mention that at our May meeting, one of the topics that came up was, "What
do we really mean by genomic medicine?"
And so we've come up with a definition that has embedded throughout the Institute, and
also with our council, and publicly.
And so what we've defined it as was an emerging medical discipline, involves genomic information
about an individual as part of their clinical care, such as for diagnostic or therapeutic
decision-making, and the other implications of that clinical use.
We recognize that this is a narrow definition, and we made it narrow purposefully so that
we could work with it within the Institute.
We recognize that there are departments and divisions and institutes of genomic medicine
that are much broader than this, but we are really sort of focusing on the use in individual
patients' care.
We also sort of wanted to emphasize what we meant by genomic in our Institute by recognizing
that there are much broader definitions.
So direction information about DNA and RNA, but as we get to sort of more downstream products,
they're a little bit outside of our Institute's immediate purview.
Recognizing that we're a small group, and so we'll kind of stay with sequence, and the
further we get from that, the less involved we're likely to be.
We also recognize that the dominant proportion of our portfolio will continue to support
the basic research on the structure of the genome and how it functions, but we recognize
we need to then stretch into these other areas.
And particularly if -- Eric described our strategic plan to you previously, and a little
bit touched on it yesterday.
We have five main areas; the last two are the science of medicine and increasing the
access to genomically-informed healthcare.
And those were -- would be the two that fit the most under this umbrella, recognizing
that the area just before that, which is the biology of disease, is probably our -- it
is our biggest area of investment within the Institute, and as well as critical in performing
the underpinnings of this area.
And we sort of view the genomic medicine implementation or application in clinical care as a key destination
for the basic research that the Institute will continue to support in our mission of
improving health for genomics research.
So that was sort of one output that came out of our -- directly from our May meeting that
we wanted to share with you.
We also just kind of wanted to remind you that we do have a working group of our advisory
council that focuses on this, and that has been a planning group for these meetings.
And so that's been one of their main functions.
But, more importantly, we use the meetings as a tool for helping them and others to provide
guidance to us in areas of genomic medicine implementation, such as, you know, what are
the needs for infrastructure to make this happen; what are related efforts that might
be related to future collaborations such as we're doing today; and, in general, kind of
reviewing progress in implementation and identifying next steps.
This is the group, and almost all of them are here today.
Jim Evans couldn't be with us.
Dan Roden, actually, we sent to a meeting in Brussels to represent the group at a European
Science Foundation meeting that was about implementing genomic medicine, and Geoff may
touch on that a little bit in what he'll be talking about.
We also established a social networking site kind of as an experiment following our May
meeting.
There seem to be some interest in doing this, although we didn't have it up and running
by May because it came out of that meeting, and so I'm not sure if it is as well-known.
And we thought it might be a nice place for if people have questions to each other among
the various institutes or centers that are doing this kind of work, you know, how do
you deal with an incidental finding of a BRCA1 variant of unknown significance, or, you know,
something along those lines to be able, to share those and kind of bat them back and
forth.
This was an experiment for us; there's not a lot on it now, but we would encourage you
to go to it and see it, and give us advice on how we can make it more useful.
This is something -- Scitable is actually a service provided by a Nature, and it's free
and very easy to use, so we thought we would try it.
We also held a workshop in September about implicating sequence variants that several
of you were involved in.
And the goal was to develop guidelines for assessing or at least guidance for assessing
the evidence implicating sequence variants or genes as being causal in a specific disease.
This is a big issue; very often you'll see publications saying, "Oh, this is it.
This is the, you know, the variant of the gene that causes X disease."
And then, you know, months or years later you'll see subsequent publications disproving
that, and so this is kind of the area of confusion that we were trying to address.
And there is a manuscript in preparation from that we hope to have out very soon.
Another thing that we've been doing is collecting recent advances, publications and other announcements
that seem to us to be sort of hallmarks of what this field can do for medicine and the
public in general.
Obviously, we find this very useful for explaining to the public, and Congress, and to others,
you know, why we're doing what we're doing.
And we suspect it's probably -- would be a useful thing for others of you when people
say, well, you know, what in this has made a difference in patient care.
And so some that we have identified, I include this whole genome sequencing in a fetus, which
is done through maternal serum rather than through amniocentesis, and now is largely
replacing amniocentesis in most cases than followed up by a confirmatory amnio when necessary.
This was an episode at -- or several episodes, actually, at the NIH clinical center, trying
to determine how this Klebsiella that came to us from a patient from New York actually
continued to spread even though every possible effort was made to eradicate the organism
and to sterilize the staff.
And ended up, I think it was growing in the drain pipe of one of the sinks or something.
And using sequencing, enabled folks to be able to trace this and how it was transmitted
from patient to patient.
This was another advance using whole genome sequencing in neonatal intensive care units
for newborns with severe disorders.
And this very recent one in the New England Journal looking at the PIK3CA Mutation in
relation to aspirin use and colon cancer survival.
So these are just examples of things we're trying to collect, and if you have an example
of something that's really pretty close to ready for implementation -- this one may be
a little bit further, maybe not -- or that demonstrates an example of implementation,
it would be very helpful if you would send those to use.
Ian Marpuri is the person that's collecting them, or you can send them to me, and we'll
try to get them up on our website, and that's down here in these numbers.
But at least the genomic medicine website of NHGRI.
Mention was made of the first meeting that we held in June 2011; we finally have a paper
out on that, it took longer than I would have liked, and my apologies for that.
But at any rate.
And the purpose there was to kind of collect what the ongoing projects were and the challenges
that they had encountered, identify some common infrastructure and research needs, and then
outlined the implementation to work for other groups that might want to apply this kind
of work.
So that's now available through -- in Genomics in Medicine.
And this just briefly summarizes what we've done, defining the landscape and identifying
commonalities, and then developing the road map.
In the first meeting, we didn't call it GM I, just as they didn't called the first world
war World War I because there hadn't been a World War II.
But, at any rate -- and then, so that was the Colloquium.
And then we followed it with GM II in December where we were looking at potential collaborative
projects and developing some working groups around those.
And then we also spent some time with institutional leaders actually asking them, what does it
take at your institution to make this a reality?
And got some very interesting insights from them that I won't review here because we've
reviewed them at previous meetings.
But that meetings is on our web, we've videotaped, or videocast and taped and archived these
meetings since the first one, so.
And then the third one in Chicago looked at the pilot project working groups and spent
a fair amount of time with payers and other stakeholders looking at what some of the barriers
were.
And that, then, led to the payer's meeting last time, which Derek -- or in October, which
Derek has described to you.
And then, of course, our meeting here really focusing on professional societies.
So that's kind of the landscape here, you know, with the way Rex has summarized it is,
you know, the first meeting, we said there's significant action in genomic medicine; in
the second, we recognize the health care providers care about genomic medicine; in the third,
that those who pay for healthcare care about it, and the professional organisms and physicians
care about it, so we're moving along, which we're very excited about.
We were a little concerned when we started these meetings that we'd get into Meeting
Hell.
I'm a big Gary Larson fan, and here you see this guy getting coffee, "Oh man, the coffee's
cold, they thought of everything."
[laughter]
And hopefully we have at least avoided that small problem, if not others.
But we feel it is worth it to get this group together, not only because of what goes on
in the main session, but what also goes on in the breaks and side meetings.
Another important thing we feel that has come out of this are a variety of funding opportunities
that we've developed based on the input that we've gotten from this community and the needs
for research.
And so I'll talk about each of these.
There's the Pilot Demonstration Projects RFA, the clinically-relevant variants resource
that Erin described yesterday.
A newborn sequencing effort that we're doing with NICHD.
And just to focus on the pilot demonstration projects, we have two RFAs out for this for
our coordinating center and clinical sites; the purpose is to demonstrate the feasibility
of and to develop methods for incorporating patients' genomic findings into their clinical
care, particularly expanding efforts and developing new projects and methods in diverse clinical
settings as well as diverse populations.
So not just in tertiary care centers, but, you know, in a variety of places.
Contributing to the evidence base to the degree that's possible, and defining and dissenting
the processes of this implementation in diverse settings.
Applications were received in July; their review has already occurred.
My colleagues Ebony and Heather are here, and, unfortunately, they can't answer much
in the way of questions on this.
Another Gary Larson: "Yes, I believe there's a question here in the back."
So they can tell you sort of what's publicly obvious.
But beyond that, they really can't comment much in this.
You know, our apologies, but stay tuned, we hope to be able to announce those awards fairly
soon.
The clinically-relevant variants resource that Erin described, I won't, you know, belabor
this, but these were the purposes of it, developing a resource that could provide information
for professional societies like yours to base their guideline development process on, and
also try to build on some of the existing programs in this area.
And those applications were received in October; the review is coming up.
Erin you've heard from, and, again, she can't say much more than, "Yes, it's a cow."
So stay tuned to that.
All right.
The clinical sequencing exploratory research was two RFAs that were actually a repeat issuance
of an RFA that was issued back in 2010, I believe, that began the clinical sequencing
exploratory research, or CSER consortium.
There was a fair amount of demand and need at that point to expand that consortium, and
so we're making an effort to do that through this.
The purpose is to investigate challenges to applying actual sequence data in the care
of patients.
And the goals would be to generate genomic sequence data that can be used in a clinical
care and that would be relevant to an individual patient; then translate these data for the
physician and communicate them to the patient; and examine the ethical and psychosocial implications
of doing that.
So a fairly ambitious agenda for that program.
Applications received in the summer; the review was partially carried out in October, was
interrupted by Hurricane Sandy, and so was continued in January.
Lucia and Brad are both here, and, again, you'll need to stay tuned on that.
And then the Genomic Sequencing and Newborn Screening Disorders RFA is something that
we're doing in collaboration with the Child Health and Human Development Institute.
The goals were to explore possible uses of genome sequence information in the newborn
period.
And these are the goals here: acquiring these datasets in the newborn period; try to understand
specific disorders that might be identifiable using sequence data through newborn screening;
and examine the LC implications of doing that.
And applications have just been received; the review is coming up.
Anastasia was unable to be here, and she will be having more information on that in the
future.
So we also, as I believe has now come of the second meeting or maybe even the first, developed
a fairly consorted effort in pharmacogenomics which I'm not going to describe now because
Josh Denny, actually, is going to describe it in a moment.
But just to point out that we are working with the Pharmacogenomics Research Network
and eMERGE, and I won't go through this, but do have a nice graphic here that describes
using this as sort of the basic foundational research where they're sort of taking a state-of-the-art
array and then passing it down to eMERGE, which is kind of the implication arm which
has less pharmacogenomic focus labs, a large patient base, and electronic phenotyping,
and can address some of the privacy concerns, et cetera, and find out, you know, how effective
and practical this is in clinical care.
So I think I'll stop at this point, and be happy to answer any questions.
Thanks.
Oh, my goodness.
Marc Williams: Obviously, it was perfectly clear.
Teri Manolio: Stunned into silence.
Marc Williams: It's a cow.
It was a cow.
Teri Manolio: Say what?
Marc Williams: It was a cow.
Teri Manolio: Oh, yeah, right.
Yeah, exactly.
Okay.
Marc Williams: All right.
Teri Manolio: Great.
Marc Williams: Thank you very much.
And if you have questions, feel free to attack Teri at the break.
All right, I think we have now report-outs from a couple of the different work groups.
So, first, will be periodontal microbiome.