 Thank you very much, Amos. All right. Yeah, I also thank you for inviting us. I mean, Amos is somewhat like a hero in our team because he is not bio-creating only solar cells, but also our registry in a way. So we get emails quite a lot when he finds discrepancies between published data and data in our registry and we have sent the task to figure out what is right. So thanks for that also. So hip scratch, however, it's very difficult to pronounce and I will go a little bit to the history why there's five consonants in a row named Aros. So, but first I will talk about this embryonic and the IPS cell lines, which are why they are in the registry, why is there is a registry about what we think about digital cell identities, how lines are registered in the registry and how we collaborate with a bank, this in this case, the European Bank for IPS cell lines. So the origin, why the human pluripotent stem cell registry exist are embryonic stem cells. And these were established in 2098. There was a first publication on human embryonic stem cell lines and then the European Union had a problem with that because the ethical issues are very controversial and different countries in the EU had different opinions on funding this kind of research with human embryonic stem cells and the European group of ethics in 2000 stated that, okay, these are cells which can not form an embryo but form all tissues of the human body in theory and any research which uses human embryonic stem should be transparent and controlled by a centralized authority. So, and then there was another opinion, opinion 22 of the same group, European group of ethics in 2007 which said, okay, there should be, to make this research transparent, there should be a registry. There should be basically a tool, a database where all embryonic stem cell lines are registered and this platform should be used then by researchers to find existing cell lines and not be forced to make new ones and also to maximize reproducibility of research, comparability and transparency. So, that was essentially the start of the human embryonic stem cell registry. So, HES-RECH is much easier to pronounce than HIP-SRECH but in 2007 or 2006 for mouse lines but 2007 for human embryonic pluripotent stem cell lines this technology was developed and for those who don't know it really, I mean probably most of you do. So, these start not with an embryo but with a, as any person, where cells can be taken, as I'm being reprogrammed, the reprogrammed cells have the same or very similar characteristics to human embryonic stem cells so they can form in theory all cell types of the human body. These cells can be made into cell types or organiates and these cell types or organiates can then be used in a lot of applications including cell therapy where they go back to a person to replace some deficient cells or help regeneration of organs. That can also now made and this puts into question the statement of the U.P. Newport-Kuboff-Essig's opinion from 2007 from 2000 that pluripotent stem cells cannot form a whole human being. They are, in fact, able to form an embryo. They can also form germ cells so spambitocytes and oocytes until now only in mice but the future will show that we can also do that with human cells so you can essentially use these cells to make a new human being or at least in the dish to a certain degree, of course, restricted by ethical constraints. So at the same time, already with embryonic stem cells there was a need by the community expressed to be able to trace where the cell lines come from so from what institutions, what lab and what donor, essentially. And now there are new applications and increasingly people already put gene editing into the cell line before it's reprogrammed so before the immortalized cells exist the cell lines are already different from the donor in terms of genetic composition so you do the, at the same time where you do the reprogramming you do the gene editing for example to introduce a disease gene or you reprogram immediately after reprogramming your gene edit immediately after reprogramming and do not care about the original line but only use the edited line. So these are issues which come up and that requires to trace in any case as you do it after donation or after reprogramming to trace back where the gene edited or genetically modified line comes from originally. So from which donor, from which original parental IPS cell lines or embryonic stem cell line. So there need to be some kind of pedigree and almost already mentioned that in his future work actually or existing works already. With IPS cells you have the additional, let's say, bonus of being able to represent large populations in the dish. Essentially you can make an IPS line from everybody for whatever application for preclinical drug testing for example to find the right drug for this particular endovidium or for cell therapies. So you represent in the dish a large part of the population and that population somehow together with the IPS line or with the models derived from the IPS lines present as we call it a bio-digital hybrid. So we have the biologic entity and two versions in the dish and so IPS derived, organic for example and as a living person and you have the digital information from both which forms in this hybrid and you can imagine that you couldn't do a lot of things with this data if they are accessible and if they are democratized as we heard on the morning. So what we capture in the registry is not only the information on pluripotent stem cells of course we do that. It's the most important part and we try to but we also try to capture information on the donor for example clinical information on the entities derived from the pluripotent stem cell lines for example organoids, on their usage for example in clinical trials and how far these cell lines are for example suitable for clinical application or not. But projects use these lines and try to do that in a way that not all this information is in the registry but linked out to other resources of course. It's just not doable but the basic types of what we register about the cell line I will come back later but it's in contrast to cello cells or only recently cello cells that allows users to register and we only rely on users to register their lines. And so you go to the website, click on I want to register a line and the first thing that happens or a clinical study or a project is that you have to create this name which is based on this needs which I already mentioned. So it identifies the institution where the line has been made and it identifies in the last part the kind of history of the line. So what was the parental line of a genetically modified line? So that's already in this name visible and until now we have enough space on that name to accommodate all the new lines which are made and we exchange, so this is one name for only for pluripotent stem cells. We link these to cello cells of course so cello cells our ID is linked to that name. We also issue when a person registered a line biosampus ID. Other information we register as mentioned here so these are information on the donor, on the contact details of where is that line when I want it, the only handling data when I want this line, when I'm interested in the line whom do we have to contact? Who generated it? Who is distributing it? Who owns it? And then of course donor information, disease status and so on and lots of data about the lines. So are these lines indeed pluripotent? What carrier type does they have? What STR profiles they have? Are there any genetic modifications? And some of these data we require, not all the data are required to validate the line and then to for example issue a certificate that these data are there. But most of them are, key information is needed. For example potency, is this really differentiated into the three germ layers, the carrier type and for example the STR profile and then come back to the STR profile a little bit later. So we have a process of then validating the data submitted into the registry. So we have these mandatory fields which I showed before which has to be provided by the provider of the data. These are then manually delegated and only after all data including the ethics provenance data which is most interesting for the funders, especially the European Union, are there, this certificate can be issued and of course we then link to supplementary data and for example publications where these lines are mentioned. So in red are the data which are needed to issue a certificate. And so STR data we require however many labs using pluripotent stem cell lines don't like the STRs. They do SNP analysis which is easier and cheaper. And in the lab that works very well but if you want to compare two lines from other labs that doesn't work. And so we insist on STR profiles. So I mentioned a little bit the ethics. So we were set out based on an ethics compromise. So the European Union wants to fund and reonic stem cell research under certain conditions. And we think that this is also very important for pluripotent stem cell lines. For induced pluripotent stem cell lines are the lines which are being used by researchers have the right informed consent to be usable for research, for the research you want to do. And this is often not the case. So what we check for the lines which want to have a certificate is whether there's an informed information sheet, informed consent information sheet. Whether the informed consent information is properly reflected in our ethics data structure and if applicable if there is ethics committee approval. And I'll be approval for that donation of the lines or making of the lines or the project itself. So some of the requirements which we need for embryonic stem cell lines for example is that the donation was voluntary, that the donation was only for IVF purposes and not for research purposes, the donation of the embryo, that there was anonymization of the donors and that was not let's say a cloned embryo. This is shown again here. I don't want to go into it too much but it takes us quite a lot of time to manually look at these informed consent information sheets and we find a lot of lines which do not have that. That don't have either historical lines which just don't have or very odd types of information. Healer line you know is a very prominent example for that. I know that companies will not use IPS lines without proper informed consent information and I think researchers also in universities should not do that. So there is alternative informed consent. For example, you can go to your ethics committee and ask can I use that line? Even though it doesn't have a historical informed consent sheet or only informed consent which doesn't consider data protection for example. And then this ethics committee decides it gives you at least some backing to use this line if it's so valuable that you have that one. So in the future we want to implement this so-called healthy hub where we for every line or the general approaches, guidelines have data on the ethics, legal and societal provenance of certain lines. You already have that for the legal environments in different countries for human embryonic stem cells and pluripotent stem cell lines. And you can see in some countries the use of embryonic stem cell lines is strictly restricted in most countries or many countries it's fine to do it to also derive new embryonic stem cell lines and in many countries there's no legislation at all. This is regularly updated. So HIPSCRATS registry has a committee of national representatives from all countries where lines have been registered as one person who helps us updating this legal framework but also helps us evaluating informed consent information sheets. So I want to go to the next what we implemented a few years ago as a clinical trial database. One of the reasons for restricting embryonic stem cell research was in 2010, perhaps, the ambiguity of benefit. So there's a promise of benefit, for example, help patients with diseases which are untreatable using cell therapy based on embryonic stem cells. But this was only a promise which was outbalanced in some countries and it requires a need to destroy a human embryo at the blastocyst stage to make embryonic stem cell line. Now we have over 130 clinical trials using derivatives of pluripotent stem cell lines about half of them from embryonic stem cell lines. So there is a balance shift. There's not only a promise of benefit but there is a concrete work into benefit. So this is a number of clinical trials in different countries. This is only from February. It increases almost monthly. Now we have 131 clinical trials in the registry and this is manually curated. So we repose information from data sources. We don't ask people who do clinical trials to register them. Also that's a possibility. So and you can see from that table that the number of applications and the number of cell types derived from pluripotent stem cells, used for clinical trials, increased a lot. So in the beginning that was like three or four diseases, mostly eye diseases, some Parkinson's and some cardiac diseases. But now we have quite a lot of applications and different cell types being used in clinical trials. So this again is a database. We started that in 2010 when the first clinical trial was adopted. In 96 trials and end of 22, now 131. 51 diseases or 54 up from 39. So this is how it looks like. It's not very easy to filter and to search but we're working on that. So we have some information on each clinical trial and of course the link to the clinical trial coordinator and the link to the other databases which have clinical trials on their platform. For example, clinicaltrials.scorp.gov or the WHO clinical trial registry. But it's very hard in these to find clinical trials which have specifically done this blue report on stem cell lines. In all together in the registry we have now about 1,000 embryonic stem cell lines and the number is almost stagnant only slowly increasing about 13,000 IPS cell lines of which only 5,300 are submitted. So 13,000 are registered without enter many data. So we, they cannot be submitted. There's a restriction on submission. You need a certain number of data already present before you can do that, 131 clinical trials. For the clinical trials, the strange thing is that we cannot find out about 30% of the cases. In 70% of the cases which IPS cell line has been used. For embryonic stem cell lines that's possible but for IPS line, this is often very difficult to find out. And we have about 2,000 certificate issued mainly for use in EU funded research where that is a requirement. So this is, you can also search by countries or how many cells have been registered in the registry per country and the most lines are from China and the US. So what is the future? So we think that these kind of registries or registries of cells are necessary to democratize. I want to use the same word as the first speaker on the field. And this is very obvious in my eyes for the pluripotent stem cell fields where data on the donor, data on the application which can be comprehended to or need to be comprehended to one cell line where the work has been done with or where the donor is known. And of course it cannot be, all the data cannot be in one registry but the registry can provide, let's see, a pole position to link to these data and find them. Cymosaurus is doing that also on a much larger basis for all cell types but we focus on pluripotent stem cell lines and we already linked to some of these resources. The hardest is the clinical resource because these data are sensitive personal data. The same actually for STR data which has sensitive personal data and cannot be as such fully public. A fraction of that can be fully public but the others at least in Europe cannot be made public because they allow re-identification in theory of the donor. So just for last slide we work in close collaboration with the European Bank for IPS cell lines which have the physical lines. We manage their data and this works in a way that the lines are registered first before they are banked in the registry. We link these information to other resources if they are there for example, genetic data in EBI and then the data is when once the data are complete for the bank the cell lines can be banked and then new data will be perhaps derived in terms of quality control which are then fed back to the registry. So now we have batch data. So we don't register publicly all these different batch data. We have basic data in the registry. The batch data are only available through the bank. So moving forward what do we really want to do the next? So we want to kind of solve the issue of data sharing even with sensitive personal data. So this needs certain conditions and I know that many institutions work on that problem to anonymize and then be able to change or have certain silos which are accessible for certain purposes and so on. We have established a data access committee which works somehow for genetic data but it's very tedious. So we want to harmonize mandatory information for the hip scratch information. So we see that many labs use different standards to characterize their lines. Many banks still use Excel sheets, many cell banks and to get these lines into a hip scratch is only possible in the moment on a manual basis or when the Excel sheet data fields are kind of harmonized with our data sheets we can import them using APIs and we increasingly use this possibility. There will be a standard by ISO on stem cell data into our ability. We are working in that and which is high level it's not so concrete. And again we want to have a legal pathway established and we do that with the US and with Chinese partners to be able to exchange data. Yeah, in the end we also wanted, so this AI, I mean increasingly we all use the AI we can search text and we can find a lot of information on a seller and searching text. So but with the AI there are two issues very important. One is the question you ask and second the data you use. And if you use a curated database like hip scratch for example, you have, you can rely somewhat on the data and you want to improve that AI usability of this database. You also want to include organoids in the database or links to organoids research and we would be happy to talk about this almost. So and we focus again on the ethical provenance issue which is currently a lot of manual work but it can be using AI for example, certain language models may be automated. So with that I would like to thank you. I would like to all the same my team. We are about six people in the moment and the IBM T4 hosting us. So this is our contact. Thank you. And the questions. You said you rely on the users that they registered their cell lines. How can you force them to do that? Because otherwise the database will never be complete. Yeah, it will never be complete. I mean, if we don't do it, we can only rely on published data. And many just don't publish the data. So we, so one incentive for registration is when funders enforce, let's say a certification by a trusted registry. And we do that for the European Commission and all the EMBL is asking for certificates. So, but this is all what we have in the moment on the side of funders to support this kind of quality control and actually our algorithm is very, very, very good. And our argument is always reproducibility. If you want to have reproducible research, you need to make sure that your cell line is biologically of high quality, but also you also want to avoid ethical problems and later on, which then translates easily into legal problems. So we also provide this ethical provenance thing. And the second incentive is publishers. If publishers and sellers knows that and our idea is very, very recognized by publishers, if publishers ask researchers to provide maybe a certificate or at least an identifier, a unique identifier that would be audio or big help and community pressure. So we collaborate with many communities. They call us a society, so to say, and hope that this penetrates more and more to them. And when we look at our numbers, indeed we get increasing numbers of registered lines, but we've been out of 100%. Yes, I have not a question about a comment with regard to the genotypes of the IPS cell lines because you mentioned it could be traceable to living persons and the stunts. So Christopher Koch and me, we shared the standard developing organization and we made it impossible because, so it's not the system of code is used by FBI nor by Interpol, so the European forensic system. So this is independent. So we share loci, yes, that's true, but it's not traceable. So we share only partially SDRs. Yeah, no other genetic information which could lead to identification. So the question is how much of the partial SDR should we share? There's different opinion in the community. On CS8, it gives you only a confidence of, let's say, 90%. Which is not identifying, but this is open to discussion. It's not trivial, yeah, other questions?