'We Are on Track towards Personalised Medicine'

Maria Poptsova

© HSE University

The International Laboratory of Bioinformatics of the HSE Faculty of Computer Science and its partners in the Genetics of Cardiovascular Diseases Consortium are working on a new project titled ‘From Sequencing to the Development of a Cardiogenetic Test’ (in Russian). The Head of the International Laboratory of Bioinformatics, Maria Poptsova, talks about the project, the results obtained, and plans for the future.

— Tell us about your new project.

— At the moment, cardiogenetics is lagging behind oncogenetics. It has long been known that cancer is a genetic disease, and projects to study cancer genetics were launched as soon as sequencing technologies became available. Scholars hoped that it would be possible to identify genetic markers for the prognosis and treatment of cancer. No one expected that cancer was so heterogeneous and that the problem would not be solved for such a long time.

As for cardiovascular diseases, we realised that many factors are involved and the spectrum of diseases itself is much wider, so determining the genetic contribution is a non-trivial task. It is cardiovascular diseases, not cancer, that are the number one cause of death worldwide. That's why we took on this task.

From the very start, we were determined to conduct fundamental research. So we had to select patients with a certain nosology (that is, not only the same diagnosis, but also similar causes, development and clinical features of the disease), conduct full genome sequencing, and identify genetic mutations. Gradually, information about mutations of individual patients for different nosologies will be collected in a common database.

Obviously, we could not accomplish our goals through the efforts of one scientific group. Therefore, we at the International Laboratory of Bioinformatics of the HSE Faculty of Computer Science started the consortium ‘Genetics of Cardiovascular Diseases.’ The consortium has brought together the efforts of cardiologists, bioinformaticians, and sequencing laboratories.

— Why did you choose cardiogenetics?

— Heart disease is the leading cause of death around the globe. And we believe that knowledge of the genetic component will help doctors clarify a complex diagnosis and prescribe the correct treatment, improve patients’ quality of life, and even prolong their lives.

Take two patients with similar manifestations of the same genetic disease, such as atherosclerosis. Since atherosclerosis is a genetic disease, we can analyse the genomes of patients and thus determine which gene mutations led to the development of the disease in the case of each patient. This will ultimately help prescribe more effective personalised treatment for them.

Maria Poptsova with workmates at the conference 'Fall into ML 2023: Conference on Machine Learning'

© HSE University

Genetics plays a role in many diseases—diabetes, obesity, psoriasis, mental disorders. And I am sure that knowledge of the genetics of other diseases can improve a person’s quality of life. More and more often, there is a need for individual treatment, which depends on many characteristics of the patient’s body, including genetic ones. We are on track towards personalised medicine.

— What diseases can be identified using your research? How often do they occur? Do they all have genetic causes?

— Today, we already know a number of cardiac diseases with an inherited genetic component. First of all, I should mention cardiomyopathies, one type of which—hypertrophic cardiomyopathy—has a strong genetic component. Other diseases include hypercholesterolemia, channelopathy, various forms of arrhythmias, and pulmonary hypertension.

Of course, diseases are not entirely dependent on genetics; lifestyle and other factors also play a big role, and that makes such research very complicated. We will be able to answer the question about the contribution of genes only after we have collected a sufficiently large amount of patient sequencing data.

— What is unique about working with cardiac patients?

— Problems arise due to patients’ lack of knowledge in the field of genetics. They do not know or understand why genetic testing is needed. They must give their consent to genetic testing, but many patients are intimidated by genome sequencing. They are afraid that it may harm them, but they cannot explain what this harm might be. Thus, we should definitely spread awareness of this issue among our patients.

Sectional session ‘Cardiovascular Continuum: From ACS to CHF’ as part of the anniversary conference on cardiology in Surgut

© HSE University

On the other hand, doctors also need additional education. Most cardiologists do not know how to use patient genome information in their daily practice. We need an expert community that will develop recommendations for doctors. And the national Ministry of Health should also approve such recommendations. We discussed these issues with cardiologists at the recent strategic session ‘The Development of Cardiac Diagnostic Products: From Sequencing to Medical Practice.’

— How does the project differ from a regular DNA test? Can a DNA test give the same results or even replace such a study?

— Today, a conventional DNA test involves PCR testing to determine whether there is a mutation at a given location in the genome.

The genetic testing we are developing can see not only mutations in a specific location in the genome, but also mutations throughout the entire gene sequence. In other words, our method has wider coverage—in fact, at the level of the entire genome.

Such tests are currently not available in clinics that offer genetic testing services. In this sense, our genetic test is as complete as possible with the current level of technology.

— How is your laboratory involved in the research? Have there been any results?

— Our laboratory has developed a flow line method that can quickly and efficiently process large genomic sequencing data. We also created a prototype of a cardiogenetic test, which included the most comprehensive range of cardiovascular diseases to date.

Our team has already implemented pilot projects on pulmonary hypertension and early atherosclerosis for a small number of patients. Currently, we have also signed an agreement on scientific cooperation with the National Medical Research Centre of Cardiology named after Academician E.I. Chazov, City Clinical hospital No. 29 named after N.E. Bauman, and Biotechnology Campus, which is implementing the ‘100,000+Me’ project (in Russian).

4th Summer School on Machine Learning in Bioinformatics

© HSE University

As part of this project, the genomes of cardiac patients will be sequenced for us free of charge, and our laboratory will carry out a full cycle of data analysis and provide the result with a list of genomic mutations. Doctors can then use it to make a diagnosis and prescribe treatment.

— How will the project develop?

— At the moment, we are accumulating knowledge by analysing data from whole genome sequencing of patients. Thus, the database of mutations in cardiac patients grows, and with it grows the knowledge base. We also already know some genes that are reliably associated with the disease, and we can already test real patients for mutations in these genes.

I see the development of the project as the simultaneous development of fundamental and applied areas. The first depends on the second and propagates it. It is necessary to both accumulate knowledge and apply it in practice.

— What final result do you expect from the project?

— The final result of our research is cardiac testing, which will allow doctors to prescribe the correct treatment taking into account the patient’s genetic characteristics. Patients do not need to know about mutations in their genome.

In some cases, knowledge about mutations can extend a patient’s life by decades, for example, if the mutation leads to impaired lipid metabolism in the blood and bad cholesterol, despite proper nutrition. In such cases, one pill a day can not only improve the quality of life, but also extend it for decades, preventing blood clots.

— What difficulties have you encountered?

— From the very beginning, we have faced financial problems. The cost of complete sequencing of one genome exceeds 100,000 rubles, and at today’s currency rate reaches 140–150,000. Thus, the whole project with full genome sequencing of one hundred patients costs 10–15 million rubles in total. Donors and investors are not ready to provide such funding.

The cost of sequencing remains high, as both sequencers and reagents for them are being imported at the moment. As soon as Russia has its own sequencers, the price of whole genome sequencing will drop tenfold or more. Sequencers are already being developed. This year, together with Russian developers, we held the summer school 'Cardiogenetics: From Sequencing to Constructing a Cardio Panel.'

The development of Russian sequencers will be a technological breakthrough, because any medical centre will be able to afford genome sequencing. Of course, efficient software products will then be needed to process large volumes of sequencing data. So we are working on such programs now.

— Which organisations are already participating in the project besides the International Laboratory of Bioinformatics? Who can take part in the project?

— The cardiogenetics consortium includes many Moscow and regional cardiac centres, research institutions, and educational organisations.

Interest in the project is growing all the time. We are constantly attracting new partners. Many private clinics are interested in offering cardiogenetic testing services, but widespread implementation is currently hampered by the high cost of sequencing.

Anyone who is involved in cardiogenetic research and is willing to share data with the expert community can take part in our project. We need, first of all, financial support—both for fundamental research and for promotion.

— What awaits the project in the future? How can it be scaled?

— The project is perfectly scalable. Each regional cardiology centre will eventually be involved in both sequencing the genomes of cardiac patients to complete the mutation database and genetic testing for known genes. At the strategy session, we agreed that it is necessary to establish standards for both the analysis of sequencing data and the set of genes that will be included in a cardiogenetic test. These problems must also be solved by the consortium.

As part of the ‘Conversation with an Expert’ project by the HSE Marketing Communications Office, Maria Poptsova has previously spoken about artificial intelligence in medicine, advanced technologies for diagnosing and treating cancerous tumours, heart diseases and lung lesions, and explained whether neural networks can replace real doctors (in Russian).