 Very good morning, and I especially thank the organizers for giving us the opportunity of this presentation first of all make the presentation and Earlier we had given the feedback country feedback rather. I should say To read the that what India requires and what are the gray areas and green green areas? So Yeah, so I'll be quite brief in my presentation. So this is basically the structure of my presentation These are the areas I'll be covering and So first of all, I'll be speaking about the strategy that is benefits and targets in the Indian context So our focus is on Transdisciplinary participation education and knowledge base coordination and Short Thank you preparing the regulatory guidelines and creating the infrastructure in the genomic area area genomic medicine area Now actually the here actually I highlight the areas likely to be benefited the diseases the predictions how it is going to benefit and the diagnostics and How increased knowledge is going to benefit us now here actually before I embark on this slide actually I would like to mention that from India. There are four major funding agencies one is the Department of Biotechnology from where I belong and another is Department of Science and Technology another is Department of Health Research which comes under Ministry of Health and Family Welfare and Another is Council of Scientific and Industrial Research that is again under a Centre Ministry so in this particular slide I mentioned about the DBT institutions and Particularly here. I would like to highlight the NIBMG and BMGC in the eastern part of our country Actually, this institution was established by the department. It has put about 50 million US dollar budget for the initial period of five years and It has a clinical attachment called biomedical genomic center in a clinical setup in Calcutta So NIBMG is located in Kalyani and its clinical wing is in Calcutta so both are functional at this point of time and in the next subsequent presentation Professor Partha will address what is doing in NIBMG So therefore I'm not elaborating on this and here I'd like to mention in the top of the area the RCB that is Regional Center for Biotechnology yesterday did mention that is UNESCO category 2 Center which has focused on education training and research and there is also an institution called Translational Health Science and Technology Institute and Also, you can see NBRC that is National Brain Research Center. So there is a cluster There and also the National Institute of Immunology. So they are all engaged in biomedical area and Recently we have embarked on a inter-institutional program on preterm birth So because India's burden is quite heavy. It's almost annually 3.5 million And there are other institutions down south and also western part of our country that that is National Center for Health Science and National Institute of Animal Biotechnology Center for DNA Fingerprinting and Diagnostics and Instem and that lowest one and the down more south is that is RGCV Tim Trivandrum Regional Rajiv Gandhi Center for Biotechnology Now in genetic cataloging of ethnic groups that these are the important areas actually data coordination Which in which will include the clinical data molecular involvement of molecular genesis geneticists and Anthropologists so creation of baseline data on various ethnic groups for disease susceptibility is very important that's what we consider and What are they actually our emphasis is on promoting translational research and That is towards diagnostic kids Then vaccine development using reverse genetics then molecular tool for surveillance and These are the some of the examples what we have been doing Now in the prenatal care area We This is also our focus and here actually On the third point we have mentioned initiating that is what I mentioned on preterm birth And we have genetic clinics at different clinical setups for screening the doing the prenatal diagnosis now in cancer genomics and Epigenomics of in genomics and epigenomics of cancer then transchromia transchromia of cancer and Nibmg is a part of international cancer genome consortium and India's Part is oral cancer which Professor Partha will be highlighting the other areas these are the areas which we want to highlight and here actually We are interested in harmonization With international ethical guidelines we have a national biotics committee and they are that department is the nodal agency Now what are the hurdles? Now these are the hurdles handling of large data set evidence for health Treatments are based on research goals Research waste due to lack of expertise lack of regulatory guidelines Incidental findings major Majority and lack of knowledge in primary health care providers So we need better technologies large data set for patients and lack of translational or interpretation and Last not the least the funding and political will Now what are the possible collaboration collaborative areas? So one comes tendering guidelines for implementation and preclinical and clinical trials This is number one number two is use of traditional knowledge and Integration into modern genetics Next one is cloud sourcing cloud sourcing for translation of genetic data Next is development of new methods of disease classification based on recently discovered genetic principles Next one is building community interest and participation Next is building data sharing capabilities Unify strategies on ongoing various places and set up biobank facilities and training of manpower and Building study cohorts That's all I want to stop at this stage now. I'll invite Professor Majumdar to Deliver his talk and together we can address the questions. Thank you All right Thank you. So you got an overview of what's going on in India in various areas of human genetics genomic medicine I just want to add a few sentences to what Mr. Sinha just spoke which is that in terms of Inter in terms of the past India did not participate in major international collaborative efforts But more recently in 2009 India did decide to participate in the international cancer genome consortium So what I'm going to talk to you about is primarily What what we've been doing in the international cancer genome consortium. So it's Probably going to be a little bit more scientific than policy or general general Discussions, I also wish to mention that there are other agencies aside from the Department of Biotechnology Such as the Council for Scientific and Industrial Research who also partner internationally and right now The CSIR the Council for Scientific and Industrial Research They have a major partnership with the Mayo Clinic on again in areas impinging on human health and and and genetics so we In India because there are multiple agencies that fund research It's a little difficult to find all of the information in one place But all that I'm trying to point out is that aside from Department of Biotechnology which was a major focus of Mr. Sinha's talk. There are other agencies He did mention some of them at the Indian Council of Medical Research Collaborates primary primarily with the World Health Organization and let me start with what the Indian Council of Medical Research has done over a 20-year period which is Which actually is the background of India's participation in the international cancer genome project so the cancer atlas of India which is primarily which is primarily an epidemiological atlas was created for a for a period of Spanning two decades and this was done in collaboration with the WHO What this has accomplished is a nationwide Epidemiological database and this goes to not to the village, but a cluster of villages. That's called a district for every every single district of India and what I'm going to try and show you are Those those graphs that pertain to oral cavity because I'm soon going to Sort of specialize in the oral cavity. So this is These these data sets are done by the ICD codes ICD 10 codes So this is cancer of the tongue and as you can see that the these are age-adjusted incident rates per hundred thousand population and As you can see that these data are primarily Done for every single district of India Clusters of villages there are certain areas that could not be covered because of political disturbance and other kinds of stuff But by and large, it's it's nearly complete. So we have this is cancer of the mouth This is cancer of the tonsil and in particular I would like to draw your attention to geographical differences even within India So for example cancer of the tonsil is has a very high incidence and prevalence in in the northeastern region of India This is cancer of the oropharynx gain fairly high There's a pharyngeal carcinoma is fairly high in the northeastern region of India The institutions that are primarily involved in cancer research To add to what Mrs. Sinha just said there are other institutions that that are outside of the Department of biotechnology who are into who are into clinical and basic research basic biology of cancers a number of institutions and then there are adjunct like technology platform facilities such as Center for whatever. I can't remember the acronym, but Molecular platform Center for advanced molecular platforms or something. It's called Then there's the Institute of Bioinformatics in in Bangalore and and CDAC in Pune. See a Center for Advanced Computing Then the focus of research is primarily Are several in terms of foresight some are based on disease burden So for example oral and head and neck cancer about which I'm going to talk to you about Cervical cancer has a major focus in India primarily because of its high prevalence Breast cancer is catching up in some areas breast cancer is even more prevalent than cervical cancer And so there is a lot of work that's going on in terms of the in with respect to breast cancer As I said the northeastern region of India. There's a very high prevalence of nasopharyngeal carcinoma gallbladder cancer, which is almost non-existent in most places of the world except that along the major river the River Ganges in In India in the Amazon basin and in the Nile Valley. You do find a lot of gallbladder cancer and so this Unique feature to gallbladder cancer in India. Well, not so unique But by and large it's focused in various geographical regions of the world India being one and so there's Some research that's going on in gallbladder cancer Gastric cancer some of the tribal populations From the from one of the northeastern states called Naga land has a very high prevalence of tribal gastric cancer And probably this is related to diet Or the microbiome. So there's some work that's that's emanating there This is a difficult region to collect data from but still some some institutions are taking major leads in collecting information on gastric cancer from there again, the gliomas has the center the Council for scientific and industrial research has a major funding as a major focus on the gliomas So the Department of Biotechnology usually Does not fund a fund glioma research because it's funded by the CSIR All right, so I will spend the next few minutes primarily on the international cancer genome consortium and India is participating with oral cancer of a specific variety called ginger buccal oral cancer And I'll tell you in the moment why we are Specifically talking about in ginger buccal oral cancer The entire project is funded by the Department of Biotechnology Which is under the Ministry of Science and Technology in India Squemacell car snow of the oral cavity is the eighth most common cancer about 250,000 new cases arise annually Two-third of them are in developing countries causes about 125,000 deaths annually It accounts for about a third of all tobacco related cancers in India The site to distribution of oral cancer is very interesting in the West predominantly what what one finds in terms of the Cancers the oral complex is that it's predominantly tongue cancer in the West and it's And and the ginger buccal complex is about a quarter In India three quarters is ginger buccal complex and only one quarter is tongue. So there is a huge difference in in inside presentation of Oral cancer the hazardous combination of course is tobacco Erica nut, which is a very highly psychoactive substance Calcium hydroxide on on a specific leaf called the beetle leaf, which is widely used So what we did was to select patients with oral cancer and do exome sequencing on the blood DNA and on the tumor DNA and I'm obviously don't have the time to describe to you in detail But these are the genes that that we found were significantly mutated Some of them are known known players some of these genes What are not known or at least until? We published our study or conducted our study these genes were not known to be associated with Head and neck cancer and we found them to be associated with the head and neck cancer and we actually the discovery sample size was 50 and we validated these results in 60 patients and This is these are the these are the genes that are significantly mutated the pathways That is most significantly mutated are of course p53 apoptosis pathway viral carcinogenesis about 20% of our Oral cancer patients also had HPV infection But so we looked at the data on those patients that had HPV infection, but we didn't find anything Anything fascinating or any anything that's deviant from the rest of the Oral cancer patients, so there was no specific association with HPV Neurotrophin signaling pathways a new pathway that seems to be altered in in ginger buccal oral cancer and Wind signaling pathway. I'm going to skip this slide. It's a slightly busy slide So essentially this is these are the genes that are that are significantly recurrently mutated in oral cancer These are the genes that where we found Copy number variations and these this is the mutational profile so you have some patients with very small number of mutations and Some with very high number of mutations and these are the sequence contexts in which the SNVs occur and If one looks at this closely, we do find Tobacco signatures in terms of the sequence context where SNVs tape or these alterations single nucleotide alterations take place The copy number variations those are the genes that are that that are recurrently found to have recurrent copy number variations In GST T1 is completely deleted in several of our oral cancer patients And the ones that are partially deleted genes that are partially deleted at these genes We obtain evidence of whole genome duplication in seven tumor samples if you look at patients and and look at profile these patients or Clustered these patients based on the mutational profiles Essentially what we find is that there is one cluster that comprises gas phase 8 and fat 1 mutations The second cluster the bigger cluster comprises p53 mutations and the third cluster contains A variety of genes that are mutated if you look at disease-free survival What you see is that there are differences in disease-free survival in these molecular subgroups if you if one Looks at patients one of those subgroups has patients with mutations in mll4 Although the sample size is small what we when we do the Kaplan-Meier we find that individuals who have the mutation Survive longer have disease-free survival of 20 months while the ones without mutation have a disease-free survival of 13 months so there is a seven month gaining of age when there is when the mll4 gene is mutated the article has just been published in nature communications and The one last point that I want to make with India's participation in the International Cancer Genome Consortium is that we have Not only contributed to the effort the international effort But I and my colleagues in the Institute and in the Tata Memorial Hospital, which is the clinical site for clinical collaborative site We've gained a lot by participating in this international consortium because we have we've been able to exchange protocols we've been able to exchange methodologies and Share data and resources so it's been it's been wonderful participating in this consortium And I do believe that when genomic medicine consortia are Cholest through the efforts of NHGRI and other international partners India will participate and will stand to gain. Thank you very much Maybe we have time for one question Which I will ask So as you know one of the focal points of what we're trying to do here is also Is on the implementation side and I didn't see but maybe it exists the linkage of the extensive cancer genome cancer sample cancer genome database to Anything that looks like an electronic medical record where you can you know about medication about treatments about outcomes and correlations presentially that would be useful for Understanding genetic backgrounds to correlate with response. Can you comment on that? So in India one of the biggest problems is that the largest patient pool Is in the government hospitals? That's where the vast majority of the patients irrespective of disease come in and that's where Electronic medical record keeping is pitiful So it's only in the private sector that there is some amount of electronic medical records But in the government hospitals virtually none the government is waking up to Understanding the importance of electronic medical keeping record keeping but it's The the this research that you're talking about is all in the government hospitals not in the private hospitals Which one well the this one the the cancer the broad based Cancer genomics program that you have is these are essentially yeah, so most of them are actually private hospitals And that's where the data are coming from because of the the quality of the data