Manage the genome
How bioinformatics helps treat serious diseases and even coronavirus
Oleg Sokolenko, Forbes, 06/22/2021
Maria Poptsova is the Head of the International Bioinformatics Laboratory of the HSE Faculty of Computer Science.
In an interview with Forbes Woman, she told how bioinformatics helps to treat serious diseases, including coronavirus, and opens up prospects for life extension, who finances such projects in Russia and why the problem of "brain drain" abroad is relevant in the industry.
– What is bioinformatics and what does it do?
– In short, the answer can be formulated as follows: bioinformatics is a science that studies by computer methods the structures and mechanisms underlying all living things. First of all, we are talking about DNA/RNA and proteins – the basic molecules of life. Strictly speaking, the beginning of the era of bioinformatics is considered to be the discovery of a four-letter genetic code by Watson and Crick in the 1950s. When the nucleotide sequences in the DNA of different organisms began to be compared with each other, and a new discipline was born.
A powerful impetus to its development was given by the development of the DNA sequencing (decoding) method by Sanger in the late 1970s. It became possible to compare certain sections of genomes with each other. In 1995, the genome of an entire organism – a bacterium - was completely sequenced for the first time. After that, the number of new discoveries began to grow rapidly, like a snowball. This was greatly helped by the simultaneous rapid development of computer technology.
At the same time, the amount of data processed by bioinformatics was initially small. Big data appeared already in the XXI century, when, on the one hand, methods such as sequencing became fully automated, and on the other, technologies for processing and transmitting large amounts of data appeared. So bioinformatics acquired its current form.
– In what areas does bioinformatics have practical applications?
– First of all, of course, in medicine. It is now clear that many diseases have a genetic nature, that is, they are either embedded in the human genome from birth, or develop as a result of mutations occurring in it. A classic example is oncological diseases. It is known that a cell undergoes many genomic changes before becoming cancerous. Her DNA changes, pieces of chromosomes change places. These processes are very heterogeneous: in different patients with the same type of tumor, cancer cells can mutate in different ways, which makes it difficult to fight such diseases.
But the DNA of cancer cells is being decoded all over the world, and now there are already open databases from which you can download genomic data of tumors, compare it with what we see in a particular patient, and better understand how to treat it. Moreover, the analysis of a huge number of cancer cell genomes, including with the help of machine learning, made it possible to identify strongly mutating foci in the genome that need to be looked at first. In 2018, scientists from the American Johns Hopkins University published an article about the possibility of creating, based on the accumulated knowledge about mutations, a cancer diagnosis panel in the early stages, when the person himself still does not feel anything and the scan shows nothing. And in blood tests, you can already find mutant DNA. I am following these studies with great interest.
Similarly, it is possible to diagnose a predisposition to many other dangerous diseases. For example, recently our laboratory initiated the creation of a consortium of scientific and medical institutions in Russia to study the genetics of cardiovascular diseases. And without genetics, it is clear that there are people to whom the risk of a particular disease has been inherited – this is clearly seen from family history. And we are combining the efforts of doctors and bioinformatics to sequence the genomes of such people and find correlations with various diseases of the heart and blood vessels in them.
It is important to conduct such research within the country. Because over 20-30 years of active sequencing and analysis of human genomes around the world, it has become clear that there is a very strong specificity in different human populations. And most of the consortium projects that generate such data and make it publicly available are made in the USA and Western Europe. It is not necessary that drugs and treatment methods developed based on the analysis of the genomes of residents of these countries will work just as effectively in Russia, where mutations may be different.
Another example is medicines: bioinformatics is able to predict how the body of different people will react to the same drugs. For example, anticoagulants, which are prescribed for heart attacks, strokes, after operations, and now also for covid – because it damages small vessels and leads to thrombosis. Anticoagulants will help one patient, another will die from bleeding, the third will have no effect at all. All this depends on mutations, several dozen of which have already been documented. This opens the way to personalized medicine, which is the future.
– Can bioinformatics also help in the fight against coronavirus?
- of course. Firstly, SARS-CoV-1 mutates: there are constant reports of new strains appearing. The genomes of these strains are also constantly being decoded and made publicly available, which is important for the development of vaccines and the analysis of ways of spreading infection. For the second year in my course, I have such a homework assignment – download the genomes of coronaviruses, build phylogenetic trees and analyze the sources of infection by country. From such an analysis, by the way, it can be seen that the virus has been introduced to many countries more than once, from different sources.
Secondly, it seems that the analysis of people's genomes allows us to predict how hard they will carry a coronavirus infection. There are already publications on some point mutations that are associated with the severity of covid. But this work is still at the very beginning: we need more data, more statistics. Perhaps genotyping will help to understand why some patients have a "cytokine storm" – this is when cytokines begin to be mass produced in the body, which should kill the virus, but instead destroy the cells of the body itself, which leads to death.
– How quickly do you think such testing of people for the risk of severe coronavirus infection can become widespread?
– Let's just say that if we increased the number of scientists who do this 10 times and, accordingly, increased funding for such research 10 times, then perhaps in a year we would have such a panel of genetic diagnostics. And it would be possible to pay more attention to people whose tests would give positive results in advance.
– Are the achievements of bioinformatics used only in medicine?
– Not necessarily, there are also related areas in which they are useful. For example, our friendly laboratory recently had a project to study Russian athletes. We sequenced the genomes of athletes and found correlations with athletic performance, endurance, and their health problems. We managed to find genetic markers that allow us to predict some of this from DNA analysis.
Now there are companies like 23andme or Genotech that offer their customers personalized recommendations on sports, nutrition, analyze the same predisposition to diseases or possible reactions to medications, even determine the origin of a person based on sequencing their DNA. We also analyze such services in the classroom, so far it's not really serious. If the results of the analysis say that you have a 15% risk of such a disease, this does not really mean that you will really get sick with it, even with such a probability. Because at the heart of all this is statistics, analysis of samples that are not necessarily relevant to you. And yet some useful information can be obtained this way.
– Can bioinformatics help prolong people's lives?
– In a sense, yes. As I have already said, bioinformatics studies the fundamental processes that underlie life, including how genome algorithms work. In fact, how to live – including how fast to age – is dictated by the program written in our DNA. It is fundamentally the same for all living beings on Earth. And if we understand how this program works, we can manage it. Relatively speaking, hacking to stop, including the aging process.
– Some futurologists believe that the "biotech revolution" will increase social inequality: the rich will have access to technologies that will allow them to live longer and be healthier, but the poor will not. It seems that bioinformatics will have a direct bearing on this. What do you think about such predictions?
– I think it's not enough to be rich, you also have to be smart at least. If a rich person does not understand how everything works, he can easily be deceived. Those who will understand how the genome works and how it can be controlled – yes, they will have a lot in their hands.
There is a lot of talk now that robots will do routine and hard work in the future. Those who will create and configure these robots will be rich and successful, and for this you need to have certain skills and knowledge. It's about the same story with biotechnologies.
– Is Russia lagging behind the Western countries in the field of bioinformatics now?
– Unfortunately, yes. There are literally several laboratories in Russia that can independently conduct experiments and generate data, which have funding for this. In Russia, it costs 2-3 times more expensive than in the countries of the "golden billion", because we have to buy all the necessary equipment and drugs from them, and this is a lot of money.
At the same time, in computer analysis, in the development of algorithms, we can compete on equal terms – it so happened that we have always had good mathematicians and programmers. Many of the data necessary for bioinformatic research can be found in the public domain. So here we just need to create conditions, including offering scientists decent salaries. Alas, science in Russia is underfunded.
– Is there a problem of "brain drain" in the industry to other countries?
- of course. When graduates who have graduated in the direction of "bioinformatics" see what salary is offered abroad and here, most prefer to go to work there. Although, for example, we have a girl in our laboratory who used to work at Facebook and Google, and now has returned to Russia. This is an exception, but it still exists.
– In the USA, many startups are based in the likes of your think tank laboratory. How are things going with this for you?
– Nothing yet. We have a lot of fundamental scientific work, and the applied work is connected with the activities of the consortium on the genetics of cardiovascular diseases, which I told you about. So we don't have enough energy to start startups right now.
At the same time, the scientific consultant of our laboratory, Professor Alan Herbert, has his own startup in the USA. It is associated with Z-DNA– a secondary DNA structure that twists to the left. Studies show that it is responsible for many important biological processes, including cellular immunity. Now Professor Herbert is actively engaged in this in his startup in America. Maybe he will teach us how to launch startups later.
By the way, to the question of the level of bioinformatic research in Russia, Professor Herbert and I met just after we created a system with AI elements in our laboratory that predicts where this Z–DNA will be in the genome. And he was amazed when he saw this development – he didn't know that we in Russia are so cool in machine learning and computer analysis.
– On the website of the HSE Faculty of Computer Science, you can see the Yandex logo. Does he or any other large company finance research in your laboratory?
– Our faculty once grew out of the basic department of Yandex, representatives of this company are on our board of trustees. But our research in the field of bioinformatics is not yet funded by Yandex. They are conducted on internal grants from the HSE.
– Have you already tried to look for investments from large companies?
– Not yet. But now we are looking for funding for our research in the field of cardiogenetics – both grants and private investments. There is a lot of work, because there are many cardiovascular diseases, and we want to cover them as widely as possible. Therefore, we are looking for money in different sources. In particular, we want to try to attract investments from Yandex and Sberbank.
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