 It's now time for a council initiated discussion, old hands of council know it and love it. This is where the agenda basically gets turned over to you guys. So this is an opportunity for you to make requests of us, oh next council meeting could we hear a report about and then pick your favorite NHGRI sponsored research program. It's also an opportunity for you to apprise us of concerns or issues that are brewing in the community. You are representatives of the scientific research community and in all areas that are covered by NHGRI. And this is your opportunity to bring things to our attention. So or anything else or anything else. Aviv. GDPR for the European Union is a matter of growing uncertainty and lack of clarity in our community. And I was curious for actually other council members thoughts as well as the NHGRI leadership on their impressions of GDPR. I can share mine. Anybody want to speak first? First of all, one thing I can tell you is it's absolutely being monitored at the NIH level. I was asked as recently as last week, is this immediately impacting any NHGRI programs? So I think everybody's sort of on edge, right. But at this moment in time, I don't have anything more sophisticated to say I don't know if Laura wants to make any comments about anything she's hearing at the corporate level, anybody on council, anything they're hearing. Is that mostly because you want to know if others or would you like to hear from somebody at the NIH level? I can add that on my experience because HCA is a task force for GDPR that is done primarily by HCA but has representation from the EU to welcome trust and other European entities, not from the NIH side. And so I can see the process unfolding in terms of just figuring out what the questions are to ask legally and obtaining legal opinions. It will have an impact on genomic research but I think at the moment the main impact that we see is that people are very confused about what they can and cannot do and what they should or should not worry about, which is a very different thing than actually understanding the long-term impact. I know that the NIH is asking those questions. We even see it in non-NGRI funded initiatives but in others that are kind of kicking off your questions about do you expect to have European Union citizens analyzed in your studies and so on. I would just encourage us to be mindful of it and maybe to have it as an agenda item later on in the year where there is a little bit more clarity. It's also going to take a while before there is clarity because GDPR gets reinterpreted in every member state of the EU, which means that it can become a multiple entity situation for genomic research and hopefully we can all be forward-leaning in trying to help sway that conversation in a productive way. I completely agree. Laura, I want to make a comment. Okay. I just wanted to agree with that and let you know that we are tracking it very closely. Sonya Juma and Elena Ganeim in our office are right on top of it and are working closely and feeding corporate NIH a lot of the information about what's going on. So I just wanted to stand up and say that if you all do run into specific situations, please reach out to the policy office. Elena will be tracking those and it will really help us to know how to best help the community in terms of where things are and then also what resources as information emerges, when information emerges on what to do to get it out to you on a way that's useful. And Laura, is it fair to state? I'm just trying to be very practical. Sometimes topics come up. You say, all right, we will bring such and such a person to counsel to make a presentation. I mean, at this moment in time, I don't think there's anybody at NIH that would, I mean, I could think of who we might bring, but there's not much to say yet because there's so much just still waiting to see, right? Correct. So we'll monitor it and then at some point, if there's something more solid to say, we could bring somebody here to say it. But I just think it's, until we know more, I think we can't even promise you when that would be. I just want to add that I think the biggest sets of questions are for those who serve data, not for those who generate data. When you generate data, your responsibilities are very clear and the likelihood that you have to intersect with EU citizens is lower and you can control it. But if you're a data repository, a major international one, this is when it becomes what is called a data controller and a data processor. This is where things get unclear and where I think we would be hit the hardest in terms of the types of resources that NHGRI is currently supporting from the data side. Mark? As long as Aviv brought up European-driven initiatives, I'm wondering if NIH has on their radar screen this open access for publication initiative called Plan S and NHGRI. So I almost feel like it's almost the same comment. I mean, in that, you know, I think there's lots of discussion about this, lots of monitoring this gets brought up, certainly at the director's level, not yet clear where it's leading and what the implications are for NIH, let alone for NHGRI. I'm not sure there's anything unique about NHGRI compared to NIH. Well it has big implications. If it's implemented, I think it has big implications for data release and data oversight and stuff. So if you hear more, I'd like to hear more about that, but not certainly not yet because I agree it's not. Sharon? It seems to me the question of variant reinterpretation came up several times today in different settings. And there is actually quite a bit of data that's been generated. I know Heidi and I wrote kind of a Heidi Rem and I wrote a perspective on this not long ago based on some papers that came out. In the clinical realm, it's actually quite common. There have been several different studies that show about 20% of variants are reclassified. That doesn't mean 20% of tests because the rare variants are more likely sometimes to be reclassified. But I don't know whether it's a topic worth discussing at council or it just seemed like it was kind of a theme that occurred in several different discussions or perhaps as we do more and more of these big projects, whether it's worth developing any kind of guidance for how projects should consider reclassification, which is very different from reanalysis. So reanalysis is more that there are new disease genes being discovered. So something that was negative may now be diagnostic. And those two terms, that was the other point I was just going to make is those two terms often get confused, but they're actually often quite different from the patient's perspective in their interpretation of it. Can you explain the implication of reclassified? Is it oops, we made a mistake or we understand this better? We have new information. Well, generally it's we have new information, but it certainly may be perceived by the patient as oops, we made a mistake. I would say one of the papers that the paper we were specifically asked to comment on looked at the rate of reclassification of hereditary cancer variants over 20 years by the race and ethnicity of the patient. And that clearly varied as different population databases came on board. Certainly the development of first thousand genomes and then exact and other population databases caused the most of these oops kind of things where things were actually called pathogenic that are clearly common once you have big enough data sets. But it's not generally that somebody made a mistake. The other thing is that the classification scheme or framework is much more much, much more complicated and the prior ACMG guidelines for variant classification were very broad. And so labs may have been very much following those guidelines, but really looking at the same variant and calling it two different things. I was very intrigued by the presentation that Hunt with Willard gave to today where he basically took as opposed to studying a variety of variants in in a setting he's doing a population application of genomics and clearly Geisinger's population is very unique. And I was trying to imply to him and I've talked offline and that is whether it is truly generalizable using the Geisinger experience. I wonder whether if you're aware of similar population based applied genomics, whether that couldn't be in the future another another type of presentation. So again, we can see different settings because it's intriguing. It's early and it is small in the actual application. But I think it's something that I would love to hear more about. There's nothing quite like the Geisinger program right now. There are a number of groups that are looking at doing something like that and a number of them that are involved in our studies. Geisinger is involved in our studies as well. But to my knowledge, there isn't anything like that just yet. And even yeah, no, I well what I know is that there isn't anything just yet. If anybody else around the table knows it knows of any, but I do know that there are groups that are trying to move forward something like that outside the US. So certainly Genomics England, which is sequencing, you know, 100,000 people and now actually is putting sequencing into their clinical care system. That's one of the reasons we have a collaboration with them. So that's one that the degree to which they will use that for research, the way Geisinger is doing is not quite as clear. But I think it's an aspirational goal of theirs, but it's a secondary goal. Whereas with Geisinger, it started with their research and then moved into clinical care. So they are, UK Biobank is moving toward sequencing all 503,000 people. But they aren't doing anything in implementation. So their approach is basically, you know, you came into a study. It's a research study and it's not for your clinical care. The Estonians are actually doing a very nice program where they sequenced 2,000 or so Estonians to develop an array that was Esto specific as it were. And now they're using that to predict clinical risk of a whole variety of diseases. Yeah, which is a little closer, I think, to what Geisinger is doing. Trying to think if there are a lot of... And the Million Veterans Program really is not about implementation. It's not about implementation. All of us, not quite clear what they will, not really implementation. They will return information, but they're not going to, you know, do it in the context of clinical care. Although there may be opportunities to build implementation programs on top of it. I think you're right, Terry, but I think some early things that we're tracking is like North Shore is partnered with Color Genomics, right? And they're just starting, Color is moving into employer population. So it's at that level. And they have relationships with quite a few employers at this point. And I suspect that over time, Invite is also going to potentially be partnering with different groups. So I think it's important to track. And you're right, we probably don't have enough experience yet. But I think we are seeing signs in the marketplace that it's not Geisinger alone. Gail. Yeah, this builds on both these prior comments. And that was my question about the extent to which the market is driving the ways that genomics is going to proceed in a variety of academic or research or clinical settings. So I was thinking about Geisinger having Regeneron be this driving force to, I mean, to sort of allow them to have the capacity. And the exchange there was simple. It seems that they get to do drug development. And Geisinger gets a return of what kinds of variants they're interested in. But because of what you just mentioned with Color and some of these other new companies, and Sharon's comment much earlier, wait a minute, are there really 900? Or was it 90? No, it was 900,000. And I think people outside of clinical medicine have no idea how many tests are being ordered. These companies are doing hundreds of thousands of, they're reporting panels, whether they're doing exomes underneath that, I can't really tell you. But in adult medicine, there is a huge market for panel testing. Yeah, yeah, well, so, but my, you know, when I was thinking about what would I love to hear, and I don't know who to invite really, but it would be to educate myself about the landscape. And I think it's a massively changing landscape. The price points are evolving and they're all kind of competing with each other or some institution to use them to do what, when, in the future, I'm not sure. But it just seems like this is such an important force now. And I don't mean just 23andMe advertising on TV. I'm really talking about public health genomics, you know, public health genomic screening, and clinical offerings that institutions would like to do, whether it's for complex polygenic traits or for Mendelian disorders. I just find this fascinating and I wish I knew a whole lot more about it. So if there was somebody you could invite who could educate about it, I would love that. Does anybody have a name of someone that would fairly and accurately describe that landscape? I could imagine getting people who would love to talk about that landscape. But I'm just trying to be fair and accurate and are hiding might be, yeah, maybe. Jeff? This is a request for a possible presentation at a future council meeting. I'm trying to learn a little bit more about this whole domain of implementation science. And, you know, the problems are classic between being able to identify tools that are determined to be safe and effective and actually getting them into people's hands. And certainly as genomics is increasingly moving into the real patient space here, I think there's going to be huge challenges with implementation. And there's folks out there with this expertise. So we heard a nice presentation at the CSER Emerge meeting by David Chambers from the National Cancer Institute. And it turns out I guess there's NIH is actually doing a fair amount of work in this space. And there's funding available that I think NHGRI perhaps has signed on to for folks to be able to get funding for this type of work. But I think it might be helpful for folks to learn a little bit more about what the, what this is all about and what the NIH is doing in this space. Thank you. Any thing else? All right. Thank you very much. I'm going to find out if we were successful at moving up the time of the bus departure. And if we were, you're going to get early dismissal. Otherwise, we're going to convene the closed session for just one more action. But before I do that, I have to read the conflict of interest statement. This applies to all the applications that you'll be reviewing in the closed session. You must leave the meeting room when applications submitted by your own organization are being individually discussed. In the case of state higher education or other systems with multiple campuses geographically separated, own organization is intended to mean the entire system except where a determination has been made that the components are separate organizations for the purposes of determining conflict of interest. You should avoid situations that would give rise to changes of conflict of interest, whether real or apparent. For example, you should not participate in the deliberations and actions of any application from or involving your spouse, child, recent student, recent teacher, professional collaborator, with whom you have worked closely, a close personal friend or a scientist with whom you have had longstanding scientific or personal differences. The NHGRI staff will determine the appropriate action based on recency, frequency, and strength of such associations or interest, either positive or negative, and will instruct you accordingly. And counsel actions in which you vote on a block of applications without discussing any individual one, the so-called on-block vote. Your vote will not apply to any application from any institution fulfilling the criteria noted above. Please sign the conflict of interest and disposal of confidential materials forms which are provided to you. They'll be collected at the end of the meeting. And this concludes the open session of the council meeting. So you're free to move about but not leave the room until we find out what's the deal with the bus. Okay. Thank you all.