 We have still one more item to cover as we wrap up and Terry and myself and several of the of the Genomic Medicine Working Group have been trying to capture some of the major themes that we Highlighted today, and I'm gonna turn the floor over to Terry a dangerous thing to do But we are we promise to end on time. That's the that's my promise to you And I only have 30 slides so it shouldn't be that bad So so what we've tried to do is capture Sort of some you know key points that came up These are not you know the most important points necessarily whatever but things that sort of you know sparked us to think Oh, this might be something we could build on or something We should keep in mind as we you know go through tonight and into tomorrow in the breakout groups and elsewhere and Very much are hoping for you to help us refine these We'll be sending these out to everyone along with a list of Sort of your assignments for the breakout groups and a roster that has everybody's contact information in it So read a chamber should be emailing that to you momentarily But we thought we would just try putting this together Just just to kind of run through and and after it in parentheses are listed the places where we heard those Comments or at least we think we did and and if that's wrong, you know At least at least the folks who were giving those presentations might know that there was something that you said that prompted us to put this up so so at any rate there there was some some Interesting suggestions about the possibility of accessing Anonymized or de-identified however you want to define it electronic medical records in some kind of a general database And we heard that not only from the UK But also from Estonia And I think there there may be some other places that are trying to do that So we probably didn't catch them all but that would be something obviously, you know Very useful models to be shared across countries for how you can do that within your country And then of course there is always the issue of how do you share data in those databases across countries? And that's one that we'll struggle with a bit We heard about a bake-off or comparison projects on both sequencing and annotation pipelines That the UK is taking lead on which is actually just doing which is which is wonderful And it would be neat if that could be a lead for others so that we could you know learn from it build upon it Etc and ways that we might be able to do that or things we perhaps we can talk about over a beer or other ways We heard some interesting models in terms of approaches to genotyping so in some places the UK and Belgium in particular It sounded like specialized genotyping centers were being established and used I know that that's that's a model I think that Canada uses as well In Singapore we heard that the genotyping would be deployed across the existing framework and in France It sounded like it was a bit of a hybrid model where where they were there were some that were dedicated centers But they were within an existing framework So again different kinds of models for approaching this but an interesting Model that we have not used in the US in terms of having dedicated Genotyping centers for clinical care. We we have obviously Competitions for funding genotyping centers in the research realm, but we haven't done that in clinical care And we may want to talk a little bit about You know that the pros and cons of those models and where that's appropriate and where perhaps not We've talked over and over about the critical importance of depositing data in ways that make it available to others Recognizing the challenges in doing that and there was you know mention of the General Medicine Alliance that that we'll be hearing about from My Greek colleague dr. Petrinus George, I think I keep wanting to call you Ari and I know it's not So and then and then also the Global Alliance for global health model. So so again how we can do that It was interesting that the comment that was made I think by one of our Belgian colleagues about looking at Next-generation sequencing guidelines for diagnostic sequencing And I think what what you said was we looked at the guidelines in the US and the UK and the Netherlands And then we kind of you know made our own and it makes one wonder Why are there guidelines that are different for diagnostic sequencing in those places? And is there some way to harmonize those or at least bring together those efforts and figure out? You know, what is it that the UK knows that the Dutch don't know or vice versa that that might want to be shared And I think we heard repeatedly we should be reaching out and we did try but we will try the more After this meeting to the Global Alliance and to the Rare Disease Consortium So is there anything there that that we got like completely wrong that you'd like to modify? Okay, all right, if not Then in addition on the and some of the international projects that we heard about There was that the mention of population-specific traits which which really sounded sort of interesting from From the Korean presentation Could we consider these in a way experiments of nature or you know certain certainly human biologic variations that we could then link To genomic variation and learn more about from a specific population these kinds of studies have been done before obviously But doing them on a genomic scale is a very interesting thought We also heard I think Korea where you were the only one that mentioned a population-specific reference genome But clearly that yeah, and you the same the same sort of thing I mean many populations are going to need that we heard about from from Gad Gad from Our Israeli colleague the challenges of mixed ancestry populations and potential stratification So they're again needing reference genomes and wouldn't it be wonderful to have reference genomes across each of these countries? That could be shared in some way you're looking skeptical Tim Could you use the microphone if you wouldn't mind it's right in front of you. We keep it handy for you You just keep talking genome reference consortium hat on that's been Trying to incorporate things from other populations and you know We kind of think that if you take thousand genomes data and beyond eventually you end up with just one big graph which will represent the entire world population and Rather than having individual ones for each country It's that graph because everybody's gonna be add mixed to some extent And that will be the thing to align it I mean we don't really have tools to deal with even the the structures within the genome reference at the moment You know people don't align correctly against all the patches But a graph is going much harder to deal with but that probably is the future in terms of mapping I mean, I guess not to drill down too deeply into this, but I mean That seems like a laudable goal, but what's the interim strategy and how long will it take? I mean and that to me seems to be there and this might facilitate country specific projects as well Irvinda you wanted to comment This gets it to a very difficult. I don't want to belabor the point, but I think since we're really talking about a Anyway, you look at it. There's some immediacy, but some futuristic Madison I think my laudable goal is what we should go for because the question is it's a reference genome for whom I Mean and and I just I just don't think that you know, this has a possibility of getting into Nationalistic labels and specific labels that is much more likely to harm this kind of personalized medicine and and and so Scientifically in every way, you know this graph representation of genetic variation all humans is a much much more Effective way of looking at it Even if the national happens to be from some other ancestry meaning a Korean of Say South Asian ancestry Great. Thank you. So we have just demonstrated that my population genetics expertise is terrible My apologies, but that's why we put these things up here So in addition, we heard about an interesting idea for a pharmacogenomics card Particularly related to a really dreadful condition and I can I was I was saying to our Thai colleagues The reason I'm in this business is because of a case of Stevens Johnson syndrome that I saw as an intern that I will Never forget and and never want to see again And and this is just a really cool idea So is there some way that that we could we might be able to build on something like that They have the you know advantage and terrible tragic disadvantage of having a very high rate of this condition And so it's it's quite relevant to them But it may be that there are other similar conditions elsewhere mark This may be the first example of a clinically a pickup applicable fee was where you pick a drug Verse event phenotype and then look for all of the different pharmacogenomic triggers or drug gene pairs that can relate to that I thought it was a really fascinating way to think about it and Then we also heard about that the interesting idea in Israel of pushing family history data So that one as I understood it when somebody has an event you push that event to their brother You know son parent whatever Into their medical record without identifying who the pro band is so that that information can be used in their clinical care without Essentially, you know removing the privacy of that of that person So that is a very cool thing that's going on in Israel and and again something that would be not that difficult to do Had if we had linked couldn't do it in our country perhaps But if there were linked databases or sorry linked EMRs across across family members as a I Should have known that Intermountain would have done it so but that that is a really neat idea one week We could think about Transport or importing and the importance of negative studies We talked about a little bit in terms of you know when people do a genetic test Don't follow the findings, you know the guidelines based on the findings and it doesn't make a difference in care That's important information to feed back to those clinicians so that they they change their practice as well as to the health care system So aside from the population specific reference, you know Were there anything else on here that people thought was off or even modification? For the panel discussion, but we had a very robust panel discussion and very much appreciate The panelists as well as those of you who participated in that We did hear from from Irene that there is a recent solicitation That's open on piloting the rollout of personalized medicine I'm sure everybody at that point went to you know Google and and looked at what you know What kinds of things were being looked at and you also mentioned that that these are designed to be international in scope Including European partners obviously, but also international partners. So something we may want to take a look at Enhancing data sharing through metadata sharing was a very interesting idea and the as I understood it Basically having descriptions of what data are available and then having individual context be made based on that So so another way that we might be able to get around this concern of you can't make all the data available to everybody Recognize the needs to harmonize policy and regulation Harmonize maybe a bit of a challenge for a variety of reasons But at least to understand the reasons for differences across countries so that that when you know an issue comes up in one country You say well, you know, they tried that in Australia didn't work or or you know It really isn't relevant to us because of x y and z and those are things that we do have a policy working group And perhaps they can be thinking about that We talked of a couple of folks here have been done and and commented on on we need to agree on what we consider to be Evidence that a variant is actionable and and that may be one that's it's going to be so case specific that we really can't have Criteria, I mean we you know some years ago We came up with criteria for what's replication in a genome-wide study. Well, that was a pretty standard thing And then a couple of years ago We tried to come up with criteria for implicating a sequence variant in a disease and that was really hard But but in terms of what is actionable and what is not it may be tough to come up with those on the other hand There could be some broad guidelines that that we could agree upon and that's something I think to think about Irvinda mentioned that we need case studies And I wanted to give a shout out to Mark Williams and the working group that he's leading in the inter-society Coordinating committee the education group that that I mentioned early on Because there's a whole use cases working group and one of the things that we're trying to do is take a standard template Send it out to you know, whoever and and ask people to really define some Use cases or case studies that will get the attention of practitioners in a given specialty so that you could have it You know an eye disease Mendelian case and an oncology, you know family history case Etc. And and those are things that I think we could you know crowdsource and get get others to help with because it is a challenge to put those together and And then the the interesting idea that again Irene suggested about getting a map of of ongoing projects So you had mentioned to something going on in the Czech Republic and in German hospitals that we didn't know anything about And and is there some way to catalog those cataloging is a painful thing, please come so that we Recently funded the project Which actually is keeping in kind of an observatory of ongoing activities in Europe on personalized medicine activities? And there you can find a lot of information about different funding schemes and also some some projects It's been European But I know that there are some information from Canada in there as well And it would be quite interesting if we could do something more on the more global scale on keeping track of what are the Ongoing activities so that's something we maybe we could discuss them. Absolutely. I think one of the action items I'm hearing emerging here is that there could be a clearinghouse function for a lot of things that we've heard about Where we could have a one-stop shop to try and accumulate that information and trying to Disseminate it more broadly. Absolutely. Yeah, and and especially if you've already funded somebody to do that, you know bravo That is great And and perhaps you might even perhaps send me or Jeff the link to that that would be that'd be fantastic. So good and Then let's see so then the second part of the panel discussion There was the question and I guess it touches on this that Phil Patrick Tan asked about how to make Those of us in this room aware of and engaged in ongoing efforts So the one that was had been raised at that point was the genome in the bottle Effort which is was to come up with sort of standardized genotyping samples that then everybody could use and test their methods against And we'll get the the reference for that I know my colleague Jeff Schloss has sent it to me and so we can we can distribute that out to y'all I hope you don't mind receiving emails from us, but but at any rate, that's you know That's something that we need to be thinking about if as we leave this meeting How do we then keep that kind of communication going without driving everybody's nuts with emails and that sort of thing? Is that a website is it's you know an observatory is a great idea those kinds of things Reference samples I've mentioned We talked a little bit about you know Could we somehow bring together all of the exomes and genomes that are being sequenced now in the various places and at least Report the variants that have been seen there so that people would know that yes This has been seen before no it hasn't whatever There are databases that are developed for that the ISCA database, which I think changed its name on the IC I see Gigi I David and David may want to comment on it could could you just Okay, so what David said without a microphone if I can repeat it is that the the initial consortium that was focused on cytogenetic Array variance is now Including sequence variances as well, and it is the international cytogenetic Collaboration of clinical genomics great. Thank you So so yeah, so so might there be some way to deposit data there or in the ClinVar database of our National Center for biotechnology information. I'm sure ebi has something similar to that I'm sorry decipher Sanger has the decipher database. Yeah, so there are opportunities there and and then you know We talked about you know We would all like to see an implementation pilot or even an implementation large-scale study But not let's not just pilot just pilot something but but obviously to pick pick the best and use implementation science methods to do that any Objections with what's up here? Yes So so and is saying is that we're basically That we didn't touch touch on the push-pull model and I have to admit part of that is because I don't understand it So so I might ask one of you to I think it was work Anderson who was commenting on that What exactly you mean by that particularly for those whose English is not their first language But even for me, I'm not sure of what you what you mean could you come to a microphone? I'm sorry to get you up at this late in the day, but it would be very helpful and might be better than me at this but really it was the issue of Generating the demand from the policymakers that they they needed To line that up with what we think they need another I'm not being very coherent Sorry, what time is it? That's just that's just an excuse I'm normally like this So so it's it's really making sure that as we discussed any discuss any of this that we Have those who have to make hard financial decisions there right from the beginning and with us because No matter what value we generate from precision medicine somebody is going to come up with that in a budgetary context and They will provide a very strong and realistic viewer priorities That might not be the same as our priorities as researchers Great. Thank you. Is that what you yeah And I think the other point there that I heard was it you know We had some countries that presented that said we have national models that you know where the government is saying you do this Others were we're not getting much response from that from the national government But where they're really going to the patients themselves and so there has to be a grassroots component of that about not only what the Clinicians and researchers want but what the patients want and what energy the patients can bring to this process So I would want to represent that as well Yeah, unfortunately, I don't have a way to edit on the fly But we'll try and make these changes. So Let's see focus on the best. Oh, and then and I think that you know the best comment that I heard all day was move beyond talking Which both our our Swedish colleague and and and commented on and I think we all recognize we need to do so Good anything else in here? We do have then there were a couple of Additional international projects. I wasn't able to catch them all but but we we did hear from from work on The a framework that y'all have produced on translation of omics into care and He'll hopefully be sending us the link for that and we can share that with y'all that sounded very very worthwhile And very interestingly a personal electronic health record that can accept genomic data That would be the I think the first one that I've heard of that can do that I don't know mark your your mr. Electronic medical record. Do you know of any that can accept genomic data? Of course in our mountain can but Can yours Yeah, okay anyway Really Super and then and then I I promised my last slide Was just a couple of additional points that didn't fit as as neatly in here And don't disappear because jeff is going to tell us what happens after this and dinner and that sort of thing Was to to develop a global you heard about the clean gen resource that that eric described to you Which is this this effort that we've begun to identify actionable variants that obviously Action of a variant depends on you know the context on the population on the setting of clinical care, etc So is there some way to to expand that to a little more global approach? We talked about pilot implementation projects a bit Um On the policy side we talked about either a standardized informed consent or because informed consent is so culturally specific Are there at least models that we can use or or some guides in that and we've taken this approach at NHGRI to say You know here are some components we think are really important in these and you can you know use those or tailor them to your own settings and then Some discussion of global EMR phenotyping standards There were universal sort of ringing of hands over how difficult this is to do But but I think you know we have some evidence that it can be done It's not impossible Particularly in dealing with electronic phenotypes and and electronic logic that that is translatable So so let's not give up on this and we have a working group addressing it and and as jeff pointed out We haven't talked about children really at all here. They haven't talked about newborn sequencing You'll hear a little bit about that the project that we're doing on on that tomorrow, but but those are other areas So anything here that Anything we've missed or Oh, well, thank you. Thank you very much. So i'll stop and then hand it over to jeff and Thanks terry um wonderful job summarizing what you know the the amount of ground Who would have thought we would have actually talked about all that stuff in one day And we have more to come tomorrow So the purpose of this again was not to be conclusive but to Give you a starting point particularly for the breakout groups where we don't want to re Revisit these issues as issues We want as we'll charge you again to do tomorrow Ask you to begin thinking about the solutions and actions that you will take that we could take as a group