 So, good afternoon. First of all, I would like to thank the organizer for this very exciting and challenging meeting, and it's my pleasure to present the National and Stratified Development of Genomic Medicine in France on behalf of these National Aliens for Life and Health Science, which has been created in 2009 in order to coordinate all the efforts in terms of health care, but also life science research, which is directed by Professor André Sirota present here. So, since one critical aspect of what we are discussing during this today's meeting is a clinical evidence, we have considered that the top priority was rare disease and cancer. Now, the national strategy was mostly inspired by the fact that, as you know, and as we are aware of that, the challenge now in this modern area of genetics is not any more the genetic variation detection, but genetic variation interpretation. I think that we all agree that if we are considering just the 1.2 of genome-corrosion due exome, we are going to identify in each exome of the patient 20,000 SNV, around 500 are rare, not present in the database, and the big challenge, especially in the clinical aspect, is to provide evidence that the SNV is involved in the disease. Of course, we need very sophisticated now statistical analysis, and we are missing at the present time in our whole countries in Europe an accurate estimate of the alleic frequency for rare variants, which we can see is below 0.1%. Of course, we need more and more very simple animal models such as zebrafish, but of course what is extremely important is the confrontation of the genotype and the phenotype, the reason why our strategy has been inspired by this challenge, and is mostly based on the development of national clinical and molecular genetic networks. So these have been performed within the framework of the French plan for rare disease. You know that in Europe we have around 25 million European citizens suffering from this rare disease, 3.5 million French citizens suffering from this rare disease, which prevalence can be estimated about 1 among 2,000, and in France under the supervision of the Ministry of Health and Solidarity and Ministry of Higher Education and Research, the big challenge was to provide expertise, but also territorial equity. It's a reason why the first action was as a first floor to create a national network of the country of what we call reference and competence clinical center for rare disease, which were split in different topics such as, for instance, cardiovascular disease or rare neurological disease, and we have over the country at the present time has conductor of this organization, roughly 131 reference center, which are going to coordinate all the competence center in order to provide an expertise at the clinical level. The second action thanks to this plan was the creation for a disease of a national networks of molecular genetics laboratories of the country, which are all specialized in a subgroup of rare disease. For instance, we have cystic fibroids, this network. We have neurogenetics networks. You will see cancer. It's outside of the fields. So this network, which has been organized through the national organization of the molecular geneticist and which is working strong collaboration with our research laboratories, which are mostly located in France in university hospitals, ensures a diagnostic of roughly 1,250 monogenic disorders corresponding to more than 1,300 gene involved in monogenic determinism, and this corresponds to more than four and red genetic analyzes, both for index cases and relatives. So we have roughly 100 molecular genetics laboratories over the countries. In the context of the technological revolution due to implementation of neck-duration sequencing, most of the laboratories are now being equipped with a NGS platform, but in the medium-sized formats, corresponding mostly to MySEC, for instance, a machine. So one important action thanks to this French plan was also the creation of the French Foundation for a Disease, which is a non-profit private structure that coordinates, stimulates, federates, and founds rare disease research. And it was very important thanks to this organization, coordinated by Professor Nicolas Levy, to facilitate access to NGS platform. And for instance, what has been done is to boost access to inter-regional platform of high throughput NGS for exome analyzes, both in research fields, but also in diagnostic fields, when of course targeted analyzes are negative. We have at the present time five inter-regional platform who have in charge to perform exome analyzes, mostly exome analyzes. Some of them are performing genome analyzes, but also bioinformatics trainings and bioinformatics analyzes. And thanks to the French plan, we had two open calls corresponding to 77 Fondant Project, and which allows us to perform more than one hundred and one thousand and one hundred exome. Now in parallel, because it's quite different, but the philosophy of the organization is the same in terms of cancer. And that was a main achievement, I think, in France. We have also what is called the Plum Cancer Consumplan, and there's a supervision of the National Cancer Institute. And the idea was also to organize these two floors, both in clinics and molecular genetics, of cancer for cancer, and that had been organized through the network of the University Hospital and the Comprehensive Cancer Center. The first floor was a network of clinical cancer genetics center. So we have now 60 clinical cancer genetics center in order to perform genetic specialization specialized in phenotypic evaluation for all the family, which are suspected to present on the basis of family background, early onset, material primary development of cancer. And we can consider that each year we have roughly 44,000 genetic sessions focused on cancer. You have here the distribution of the men and secondary clinical cancer genetics center. Similarly, as the second floor, we have now a national network of molecular genetics laboratories for inherited form of cancer, of course, for link syndrome, inherited breast, and over in cancer, but for all over a more rare, mundane form of cancer. So we have now 25 laboratories. For instance, we have in France 14 laboratories, performing the BRCA1 and BRCA2 analysis. We have 12 laboratories performing colorectal cancer gene analysis, and the 73 gene are going to be analyzed and corresponding per year, both for index cases and relative to 60,000 genetic analysis. So one action, thanks to the initiative of the National Institute and on the science part directed by Professor Fabien Calvaux, was of course to structure the next generation sequencing both at the germline and also at the somatic level in term of the targeted therapy in order to detect on the routine basis all the actionable mutations. And thanks, there is now a recognition of different platforms. And we have now nine NGS and biophobatic facilities in order to demonstrate the implementation of the structure through the country to perform exome sequencing, comparative exome sequencing between primary tumors, metastasis, and germline DNA, and of course to perform exome analysis from germline mutation detection in the context of a strong suspicion of inherited form of cancer if the targeted analysis are negative. One important mission of this network is also to perform training to biophomatic analysis and with a strong commitment of the clinician in charge of cancer. So if we are seeing what is clearly missing in France in contrast to the marvelous presentation that we had for instance in UK or the Netherlands are also very powerful is we miss definitely at the present time her national platform able to perform very high throughput NGS facilities. So we can consider that we are okay consulting the first step which is a national network of laboratories performing targeted analysis and using NGS, not only in the context of rare disease but also in the context of rare of cancer both for somatic and germline. We are okay in intermediate platforms able in complement to the first one to perform exome analysis but in contrast to the UK organization we are missing a very powerful centralized platform able to perform exome and general analysis with a clinical grade in order not only to perform genetic discoveries but also in order to be able to provide a molecular diagnostic and we have estimates that what we need per year if we are considering both what is needed in terms of rare disease but also in terms of cancer is between 10,000 and 50,000 exome per year. I'm just restricting my comments on exome not for general considering the challenging aspect of genetic variation interpretations. So one possibility which is strongly considered as a present time and that's the main challenge of Avicen today in order to to optimize this pipeline in France is in fact to reinforce the national center of genomics in every every in the south part of Paris. So this national center of genomics which is at the present time equipped with sorry with three isek 2500 14 isek 2000 but only eight are devoted to human genome one proton 11 mysek her able to ensure within two weeks roughly a throw database a 6600 gigabase correspond roughly to the second european sequencing facility and one important aspect is that the national center is fully equipped with a high performance computing center with a total capacity of 120,000 computing cores but the case is to genomics we have 3000 cores corresponding to five petabytes and ensuring exome and who general analysis and this is coordinated by Jean-François Deleuze so the idea for the future is probably to reinforce this feature so to finish my talk the idea is to complete the pipeline so the idea in our strategy first focus focus on rare disease and cancer is to have this pipeline organization we start first from national networks of clinical centers both in the field of rare disease and cancer in order to ensure a phenotypic expertise then we are performing a first level of targeted analysis thanks to a national networks of medical molecular genetics laboratory and after that at the present time we are benefiting from national networks of international platforms in order to complete the analysis by exome sequencing analysis and training but the challenge is the creation of the national platform performing exome general sequencing analysis the big issue will be of course detection and interpretation of genetic variations so that would be one important aspect of this international platform which are going to be trained people's in order to ensure a first step of bioinformatic analysis but the big challenge after that will be to transform this variation into a clinical markers and that will be the work of the national network in order to validate on the independent samples and to go back to the clinician and one important aspect and that will be my last slide and of course if we are here dealing with genetic medicines we have a strong implication in France with genomic research which is supervised by inserm and we have considered that the top priority was of course the national development of this exploratory techniques in order to optimize the detection of disease the identification of the genetic determinants of disease and one important aspect is of course the development of bioinformatics and both statistics so I will stop here and be happy to have any questions thank you for your attention may I well my question is how much amount of money was invested to organize these genetic test centers including supercomputers and sequencing facilities if possible if you could separate the sequencing facilities from supercomputers I will be able right now to give you an accurate estimate what I can tell you is what was a challenging aspect was how are we going to reimburse all the genetic test so the way it has been organized was the following we have convinced the ministry of else that we should organize that as a national level so in other terms we have here a map of specialized molecular genetics laboratories each of them there are we are getting some money based on from directly from the ministry of else based of an annual report right and based on the report so we are supposed to perform all the analysis for the countries on a free basis okay so for instance considering the equipment so we have different calls corresponding to for instance the last call was roughly 10 millions of euro in order to have an equipment of a mysec of medium size platforms and now if you are considering the main center corresponding to as a center located in every most of these equipment have been based on either private funding or national funding or even european contracts I see the the computing part is a centralized what distributed well there are different scales so we have the main power is located in every but as you have understood since we have five uh inter regional platforms we have different bioinformatics facilities and we have considering that even playing with the mysec it was very important to have bioinformatics so we have pushed and we succeed to have permanent position for bioinformatics not only working in research laboratory but bioinformatics people working in in diagnostic laboratory because we need quality reports and as you know that's correspond to different challenges yeah thank you very much so you know we have 23 clinical genetic centers in the uk you've got a lot more in your distribution so and we've been thinking that 23 is is a lot particularly with ngs but so your system must be more fine grain the smaller number of tests per center or you're doing more tests and you know it's another problem with we're having 23 is they tend to do their own thing in terms of working out protocols and developing bioinformatics are you controlling your large number of centers so they use common platforms or maybe the way I presented is only to be confusing because definitely most of the center are located with new real estate hospital for real disease right and we have 26 so you have 23 so it's the same scale all right so you understand but you had larger numbers for the disease because within the university hospital we are going to have for instance a competent centers working on neurological disorders but usually you have a local interactions so what you have to consider at the territory level we are dealing mostly with 26 university hospital in which we are going so it's the same scale right at the clinical level that in the UK that I know a little bit all right okay