Contents
Research that uses genome-wide sequencing can provide information for the diagnosis of many rare genetic diseases. They are an indispensable element of modern cancer diagnostics and treatment. Personalized medicine is based on the selection of an effective drug based on the analysis of the entire genome of the patient. It is the genes that tell you how to effectively treat the patient, and which drugs should be avoided, because not only will they not work, but they can even be toxic.
Scientists from the Poznań scientific startup MNM Diagnostics specialize in this subject. The joint venture brought together outstanding specialists, enthusiasts, dedicated to their work and mission. The company’s founders have research work at the University of Oxford, and their team consists of people with many years of experience gained abroad, including at prestigious universities in Cambridge, Bergen and Georgetown.
Secrets of our genome
MNM Diagnostics specializes in oncological diagnostics based on the analysis of the whole genome. It is one of the first centers in the world where it is possible to perform such comprehensive and modern tests, and additionally, they are available to every oncological patient. What is the uniqueness of this solution?
First of all, on the amount of analyzed data. Scientists from MNMu do not analyze several genes or even all of our genes. They analyze the entire genome of a man and his cancer at once, which is a huge amount of data.
The genome is the entirety of the genetic information contained in all the cells of an organism. This information is recorded on a special medium – DNA. Each DNA molecule is made up of billions of tiny building blocks called nucleotides. It is the specific sequence of nucleotides that carries with it the actual information necessary for the proper functioning of the body’s cells. Reading the exact sequence of all the nucleotides in an organism’s DNA is just genome sequencing. Interestingly, only slightly more than 1 percent. genome encodes information about the structure of specific proteins. This means that only about 1 percent. of our genome are genes!
The functions of the remaining 99 percent. genome remained unknown for many years, and some scientists even considered that non-coding sequences were useless. The extremely confusing term ‘junk DNA’, or junk DNA, was created to describe what we just didn’t understand. Only recently have it been proven that many of these sequences play a key role in regulating the entire genetic machinery.
Find out what your risk of cancer is. Buy a diagnostic test package for women
Study a selected gene, several genes or the entire genome?
Whole-genome sequencing (WGS) for diagnostic purposes still remains abstractly for a large part of the medical community. It’s more of a SciFi element, not reality. For the diagnosis of genetic diseases in the most modern facilities in Poland, tests based on the sequencing of one or several selected genes (about 0,001% of the genome), at best of the entire exome (about 1% of the genome), are still performed. Such tests are often enough, because knowing the patient’s ailments, we select only the genes that are important for analysis. This saves both time and money, which is of great importance since the payers are often the patients themselves or – in the case of rare diseases – their parents.
The technique of sequencing selected genes or exome, however, has many limitations. For example, it is difficult to capture larger abnormalities, such as mutations called structural rearrangements in the genome, which are changes in the structure of DNA and may include, for example, cutting out a fragment or duplicating it. In addition, the technique completely ignores non-coding regions, which often contain information regulating the action of particular genes.
Why are these elements so important? The information contained in DNA is one thing, but what proteins will appear in a given cell is another matter entirely. Different cells have different needs, so it is impossible to compare a skeletal muscle cell to a liver cell. They have completely different functions and structures, and therefore the regions of DNA crucial for the functioning of a given cell will be completely different. This is just the tip of the iceberg, because the processes taking place in cancer cells, and therefore also the genome of such cells, remain the most difficult to understand. Every cancer is a disease of our genome, it develops due to certain genetic mutations.
– Today’s genetic diagnosis is based on the analysis of up to several dozen genes. Soon, an ever-larger genetic panel will be the standard, and consequently the entire exome will be analyzed. And further, due to the limitations of sequencing only the exome, we will eventually come to a point where the genome will play a key role. We decided to skip all these transitional stages, which consume unnecessary time and finances, and offer patients the largest, most complex and, at the same time, the most complete diagnostics – says Dr. Paweł Zawadzki, CEO of MNM Diagnostics.
The scientist argues that whole genome sequencing can be cheaper than the analysis of only selected genes, and the information obtained can significantly affect the health of cancer patients and even save their lives.
Complex algorithms and insightful analysis
MNM Diagnostics was established only three years ago in order to provide all patients with the most modern and accurate oncological diagnostics, based on the analysis of the entire genome of the patient and his cancer. Young and brave scientists join forces to change the face of Polish genetics. Such actions, however, require not only courage, but most of all knowledge, skills and … faith in the success of the undertaking, which in Polish conditions is sometimes the most difficult element.
At first, the idea seemed so complicated and crazy that everyone was operating remotely, scattered around the world, connected by the Internet (and genetics). The first genomic analyst employed in Poznań, Adrian Lejman, admits that it was not a path full of roses:
– During the first two years, we made tremendous progress in terms of the capabilities of our analytical tools. Definitely – it is happening.
At the moment, the team consists of several dozen people, some of which work directly on the genomes of oncological patients, and some are constantly developing proprietary diagnostic tools used in the company. They are so good and modern that the largest pharmaceutical companies in the world have already become interested in them, because they allow you to read key information from the genome regarding, for example, the best treatment methods for a given patient.
Bioinformatics and programmers who constantly learn the secrets of genetics, as well as biologists and doctors who must fully understand the entire automated process of analyzing a single sample, join their forces on the interdisciplinary battlefield. – Sequencing the trial is just the beginning. The results must be normalized and appropriate filters must be applied so that the analyst is able to extract any information from the file. This is what my job is all about – I develop and improve bioinformatics algorithms that allow you to find information that is diagnostically useful and separate it from information that does not carry material that is important to the patient – explains Dawid Sielski, one of the longest working programmers at MNM.
The enormity of the challenge that bioinformatics with MNM take up every day is illustrated by the fact that our genome consists of 3.2 billion pairs of nucleotides, i.e. small chemical compounds that build DNA like bricks. In order to perform diagnostic tests, the patient’s entire genome must be aligned with the reference genome – or its own healthy genome. Two genomes differ on average by 1%, which in practice gives us about 4 million letters (bricks) that will be different. Such a single nucleotide change is called a gene variant. Usually, we do not even know that we have such changes, because they do not cause any symptoms, but there are situations in which they can cause serious illness. In many cases, certain gene variants are responsible for the degree of enzyme activity, which may contribute to the different metabolism of the same drug by two different people. But not only the drug. The last high-profile project of scientists from Poznań called Our Genomes (www.naszegenomy.pl) concerned the differences between the Polish population and other world populations, and it turned out, contrary to popular opinion, that alcohol metabolism is not outstanding among representatives of our nation.
Every cancer is a genetic disease
An in-depth analysis of the neoplastic genome helps in the selection of an effective treatment method for each patient individually, and in the long run may also allow for the identification of completely new therapy targets. After all, not only protein-coding sequences are subject to research, but also all regulatory sequences, such as miRNAs. It is enough for a small element in this maze of events to get disrupted and the cell can no longer function properly. Under normal circumstances, such a defective cell dies, giving way to a new one, but cancer cells multiply indiscriminately. They are like a deadly parasite.
The entire process of neoplastic transformation may unfortunately be the result of just one mutation and an unfortunate sequence of events afterwards. Such a pathological change in the genome may be acquired during the life of an organism (e.g. as a result of smoking cigarettes) and occur only in one specific place. So if we want to diagnose cancer and analyze only a few related genes, there is a good chance that the test will not give us any answer. It may turn out that the sequence in the analyzed, selected genes is correct, and the gene is non-functional anyway, because the mutation is located in a completely different place responsible for regulation. This is why viewing the genome as an integral whole is key to understanding how each tumor works.
What is the procedure for examining the whole genome? – Two samples are taken from the patient: one from the peripheral blood and the other from the neoplastic tissue, usually a biopsy or a section taken during surgery. We are interested in what mutations took place in cells that led to the formation of a tumor. Thanks to this, there is a chance to precisely detect a defective cellular mechanism, which can be “hit” pharmacologically in order to destroy only cancer cells – says Dr. Maciej Dąbrowski, genomic analyst, who also serves as the main scientist training doctors throughout Poland in the collection and preparation of material for such advanced genomic research.
If you stop, you start to move backwards
How to get experience while navigating the white spot on the map? – Of course, we started by analyzing our own genomes, and to this day we already have several thousand complete analyzes. This is one of the highest scores in the world. For us, it is also enough to know how we should improve our tools. We are constantly gaining knowledge and improving – proudly explains Dr. Paula Dobosz, director of scientific development at MNM Diagnostics.
Genome-wide diagnostic tests are not common today, but the scientific world no longer doubts that they will soon become commonplace in diagnostics. The first president to recognize the value of such analyzes was President Barack Obama, who personally contributed to the drafting of many laws and regulations related to whole genome analysis, including the launch of the All of Us program. It was the first major science program where each participant received full feedback in return for donating their genome to science. It is worth remembering that the fact of anonymizing genomic data is a procedure that exists to protect the research participants themselves.
Savings for the system, health for patients
As with any modern and breakthrough technology, whole genome diagnostics has its drawbacks. The first is the need to perform a test based on DNA isolated from fresh material, so a fragment of tumor tissue from a paraffin block is absolutely not suitable, because the DNA damage is too great. The second is the high cost, which unfortunately is still borne by the patient. However, the high efficiency of the method means that more and more clinical centers decide to introduce whole-genome diagnostics to their offer, looking for financing opportunities together with patients.
Therefore, the next step will certainly be the implementation of the analysis of the entire genome of patients into the health care system, which will allow for enormous financial savings for the system by increasing the effectiveness of treatment, reducing hospitalization time or increasing the life expectancy of patients. We are already seeing the first such attempts in the Netherlands and Great Britain. Scientists from the British Isles, inspired by the 2012 Genomes Project, which ended in 1000, have set themselves the bar extremely high and want to analyze as many as five million of them. Any patient of the NHS (National Health Service), i.e. public health service in the UK, can apply to the project. The world of science is eagerly awaiting the results. With the MNM team at the helm.
This may interest you:
- Eat as often as possible. These foods reduce the risk of cancer
- Colorectal cancer develops quietly over the years. What are the symptoms?
- How can you recognize cancer? You must do this research