 Thanks to Eric, Jeff and Terry of course for inviting me here and I'm going to talk to you about today something that we're not doing just in Greece but it's an initiative that spans hopefully around the globe and it aims to bring together developing and developed countries. I'll start with an historical perspective. Hippocrates several centuries ago said that it is more important to know what kind of person suffers from a disease and to know the disease that a person suffers. So it's a kind of an introduction of the notion of personalized medicine. The Genomic Medicine Alliance is a relatively new initiative that aims to build or strengthen existing collaboration ties between academics, researchers, people from the regulatory agencies and the general public that are interested in all aspects of genomic medicine and in particularly how you translate research from the results from research into something clinically meaningful. The Alliance is an international scientific research network. It has nothing to do with the traditional notion of a scientific society. For example, you can see here that the registration is free of charge so there are no registration fees and this is to encourage participation of researchers from developing and low income countries. The research activities are self-financed by participants own funding sources and partly funded by the Golden Helix Foundation which is a London-based UK charity. Of course, we hope in the future to be able to create networks that we could apply for funding from other sources as well. The scientific coordination of the Alliance is provided by the Scientific Advisory Committee which is formed by 13 internationally known scientists in the field of genomics research and the administrative assistance which is of course a pain for us researchers is provided by the Golden Helix Foundation staff so they do the dirty job for us. So what are the two key elements of the Alliance and in the in the mails that we received a few months ago by Jeff and Eric they split the notion between genomics research and genomic medicine. Some Greek, ancient Greeks like to create temples so if we depict these notions as a temple genomics research as the basis the genomic medicine is a roof of the temple and to have them in between you need to have some pillars. So the pillars that lead from genomics research to genomic medicine is pharmacogenomics, genetics, ethics in genetics, public health genomics, increasing the genetic awareness of the general public and education of the healthcare professions actually those two go together and last but not least the economic evaluation in genomic medicine. And in fact the genomic medicine Alliance focus in this particular part to creating pillars to strengthen transition from genomics research into genomic medicine. The second aim is to bridge developed and developing countries. So what a developing country could gain from a developed country of course it's tech transfer, knowledge transfer, training opportunities people from developing countries could go to develop countries and get trained in central of excellence but also developed countries can benefit from developing countries by providing cases with very unique features that you could study on a genomic basis. A well-defined populations for example the gypsies in Europe which is very well-defined population group and of course partnership to grant applications because some grant application has a term that you should have developing countries as partners. And of course I'm very pleased to be part of this initiative because in all of these places that I've spent my scientific career we for example Patras we had the largest cable bridge in the world Rotterdam a caliary in Italy they all have bridges so I feel some kind is like a destiny to be part of this effort. As I said the scientific board runs and supervises the aims of the Alliance and we have six working groups genome informatics, pharmacogenomics, cancer genomics, public health genomics, genetics and economic evaluation in genomic medicine. And as you can see here the scientific board is it's it's really international coming from the Middle East the UK developing countries like Slovenia the US and so on even Japan as you can see here, Mike Lee. The members basis has a kind of a pyramid structure so you have the scientific advisor committed that it is on the top the supervisor the scientific project you have the senior national representatives and the working group leaders that they are in the middle and then you have the regular members and if you look in numbers then you see that the total number the total membership is almost 180 people from 53 countries that's actually updated since last month but the genomic medicine Alliance is relatively a new initiative so we hope that in the future this the membership basis will be further expanded. I can I can show now some projects that we undertaken the first player the first pillar which is pharmacogenomics the determination of the incidence of pharmacogenomic biomarkers in some European populations we wish to provide the proof of principle for the use of whole genome sequencing for pharmacogenomic testing and to establish a detailed correlation among genomic biomarkers and adverse drug reactions in European and Southeast Asian population that's a project that's run by Mike Lee in Ricken Institute in Japan. So the European Geeks project which is part basically of the of the PGini the pharmacogenomics for every nation initiative aims to collect on average 50 people as the first year and 500 people the second year from developing countries to carry on genotyping in almost 2,000 pharmacogenomic relevant variants in 230 admit related pharmacogenes that's basically the D-Met plus chip by AFI and based on these results to assist in prioritized medication selection in developing countries that's again in collaboration with the PGini initiative and to develop of the shelf solutions for pharmacogenomic testing in developing countries for those countries that cannot afford to be tested by whole genome sequencing force and this is the overview of the participating countries in Europe this this plan is bigger if you see it worldwide those are the PGini sites which is controlled by the Golden Helix Institute here in Athens and these are the sites where we hold some educational activities that we're going to mention to you in the next slides and these are some preliminary data you see for example some unexpected correlation between countries that you would normally expect to be you know close together like Serbia Croatia they're not lying up together and as you can see of course here that something you expect that all European countries they cluster together with the Caucasians but of course we should all keep in mind that we may all these countries maybe Caucasians that have significant differences and this can be over 130 pharmacogenomic biomarkers in each population and by replicating these findings to a larger population sample could we hope to be able to establish common grounds to provide pharmacogenomic testing in these countries the second project involves the application of neck gen sequencing in the area of pharmacogenomics this exercise involved a bit less than 500 genomes that were sequenced in a complete genomics and in a coverage of 110 X so that's a high accuracy we analyzed all the variants in the 231 D-met plus genes we perform in silico analysis to provide to have a basic level of functional evidence of the causality of these variants and we replicate independent defined things in the seven members Greek family this this is gonna it's it's gonna appear in pharmacogenomics in in one of the next issues and these are the preliminary data in the most common the most well-studied pharmacogen so this is it to the six as we all know it's involved in the metabolism of more than 200 drugs this is a total number of variants that you detect by whole genome sequencing it's on average 18,000 per individual 16th and a half thousand are novel potential in functional variants with a bit less than a thousand with high frequencies and four and a half thousand potentially novel in the exome now if one would would analyze each genome by the D-met plus you could get just 250 snips and D-met plus is the most comprehensive platform existing today so this is the D-met coverage as you can see here this is the this line are the novel variants these are the ones I'm sorry these are the novel variants these are the variants that they have frequencies of over one percent right so you can see that that basically next gen sequencing as you would expect you get the complete picture of a personalized pharmacogenomics profile the genome informatics working group we aim to develop we we currently develop three new national ethnic genetic databases to document the incidence of these diseases in these countries we migrate five existing national genetic databases into the upgraded version of this software we aim to develop an electronic molecular diagnostic assistant to translate pharmacogenomics results into a meaningful format for clinicians and this project is partly funded by this this grant here and we wish ultimately to establish a whole genome national data repository to provide other frequency data in an aggregate level we close collaborate with major research initiatives such rd connect like erdick in the areas of harmonizing and develop common standards for database and patient registries for a disease to develop clinical bioinformatics tools and including data mining and knowledge discovery tools for analysis and integrating molecular phenotypic data and to endorse scientific and educational meetings and this is how the fine base database looks like this is how you document frequencies of causative mutations this the way that the you can query among this this data is really dynamic it's a pity I don't have a video to show you but it's really dynamic having all these little boxes here rearranging depending on the on the query and this is what the immodia platform would look like this is just a mock-up you're going to have three different ways of logging in as a medical professional for research and as a patient and to be able to access the data you could basically two cards one from the patient one for the physician it's like activating the missiles yeah okay sure now in terms of public health genomics we have undertaking national wide studies to better understand the level of general public awareness and healthcare professional education over genetics this this data will be published in the first issue of personalized medicine this year we have engaged into a stakeholder analysis to determine the measures that need to be undertaken to expedite genomic basics excuse me genomic based medical decision-making process that's a paper that is in preparation for this we used a software that is used by American politicians to be able to project how the general public will feel before and after right we encourage and facilitate the coordination the coordination of educational events over pharmacogenomics these are the golden helix pharmacogenomics days in various European countries we currently have organized 13 events in eight countries including mostly developing countries but also countries like Amsterdam and the one that's come in 2014 in Cardiff in the UK this is a genetics part surveying the landscape of the of the direct to consumer and over-the-counter genetic testing in various countries and we work together with national genetic societies to try to determine guidelines for ethical legal and social issues pertaining to genetic testing that's a recent article we got in human genomics about the OTC genetic testing with a very catchy title as you can see here and the economic evaluation last but not least cost effectiveness the cost utility analysis to be able to demonstrate that indeed genomic medicine could could really bring a benefit to the patient and also to the national healthcare system we have project focusing on anti-coagulation treatment in several countries from the Balkans and also there is an endorsement of reproduction of a textbook that's going to be published by Elsevier early 2015 we organized educational activities that's going to be a summer school which will be organized this year in an island island close to Athens as you can see it's it's really miserable you know very blue waters very green area you know hopefully you can make it and also we encourage the development of a special issue about in personalized medicine with the tentative title of working towards personalization of medicine that's going to appear in September 2014 now regarding future plans we wish to expand that membership basis particularly with members from developing countries in the Middle East Asia Latin America and Africa to partner with other multinational groups like the European Alliance personalized medicine to pursue common goals to expand education and outreach activities not only Europe but also Middle East and Southeast Asia and to establish in collaboration with the foundation short and long term research fellowship for graduate students to do in fact part of their work in centers of excellence abroad and last but not least to affiliate with Elsevier to open access genomic journal as the official journal of the genomic medicine alliance and hopefully we can reach an agreement with this to this level in fact really soon so I think that's about it and ready to take your questions thank you very much thank you that was great and I'm available to teach in September so yesterday we talked about a number of issues that that that this field faces in terms of informed consent data sharing and liquidity have you solved these problems across these that you know the Pijini and other the network that you're creating you know where you have standardization of some of the informed consent data sharing agreements in place I'm just curious as to where you stand with respect to the kind of things that we're struggling with you know in this community so since we're talking about Pijini we made sure that in the in the in the sample collection we only document gender and age and these are basically adults so we make set we make we try to ensure that every country that participates in this initiative they have the proper consent so the in fact the the the Pijini coordinating center and the regional center receives a samples on the understanding that all the the proper informed consents are taking and in the majority of the case we have also the informed consent sent to us in local language of course so if it is a consent in check I couldn't of course make you know what it means but at least we know that the consent is there and so we rely on the partner it would be ideal to have a kind of of a general consent to be used we don't have so far I'm not sure if Howard wants to comment yeah we we have and we have general principles that it need to be in the consent in terms of the the ability for the data to be shared at least at some level we use we've used regional centers so that we try to make sure that samples don't go all to one place so we try actually try to keep the samples from going to the US partly just for political reasons there's been too much of a of a colonialist approach by American scientists in the past and so trying to make sure that doesn't happen like the work you're doing in Kazakhstan and some of the other aspects when the when it comes down to it's the local ethics committee that it rules the day we have to have approval at in the United States for example at University of North Carolina or now at at University of South Florida but the the one that is really consenting the patient is they usually a national or regional ethics committee in that individual country so we we have principles for them but we don't write the consent for them for PG&E anyway no so so it seems like the things that you're doing a lot of them are the kinds of things that we were talking about doing here which is great and you're sort of out of the gate considerably ahead I I wonder you know in some ways when you're dealing with kind of smaller nations that may be a little more flexible you can do stuff that may be much more difficult for the developed world to do so so so we respect that and and I'm wondering you know if you were to partner then with with some of the larger do you feel you might lose some of your flexibility and nimbleness and some of the you know really the culture that you already have how would you keep that to be honest if I speak personally I always feel that one plus one makes free so I wouldn't I wouldn't really fear that we lose flexibility what I really envisage is that we can achieve more so I see this whole initiative as as a way to complement other initiatives like the global alliance I I really feel that this initiative is it addresses a niche which is how to to bring genomic the developing countries closer to the genomic medicine by having to gain experience from countries that I have already sorted this out for example countries like it's been from my own country you know countries like Greece they can they can gain from the experience of the Netherlands or from the US so how you could you could manage to get the genomic medicine into the mainstream process in anti-coagulation for example or how you would address initiatives regarding in fact better regulating direct to consumer testing on the other hand you know developed countries can also gain from developing countries so I we hear we heard yesterday in a talk that using European Caucasians so what so who can be defined as a European Caucasian you have British you have Greeks you have Russians they all Caucasians but they have different frequencies in terms of markers and in the overall genetic makeup so I see a kind of a bi-directional benefit and ultimately the patient gets the best and genomic medicine goes further as Francis said also yesterday amazing to me that you think that developed countries have solved these problems because because I think you know you're hearing from me yesterday and today that none of us really have solutions to many of these issues so so I'm not sure we you know that the developed countries have a lot to bring other than slowing you down but it would be it would be wonderful to be able to develop some kind of a partnership it would be great I in fact I fully agree with you because I remember last year we were in Zagreb in Croatia and we're sitting at dinner and somebody said that well we actually have our national health care system reimbursing pharmacogenomic testing and it was done yeah so you hear from these countries and I'm not sure how the situation is the US but in Holland for example you can get this you can get this reimbursed so things are somehow structured I truly believe there's the common grounds for collaboration between those from rich countries and poor countries developed and developing so yes we could we could definitely explore this possibility thanks very much