Laboratory for Omics Technologies and big data for Personalized Medicine and Health

Scientific results:

During the project implementation highly multiplex methods for quantitative proteomics and measurement of the concentration of potential biomarker proteins in blood and other clinically relevant biological samples has been developed. To analyze an extended panel of proteins (more than 1000 in combination), a new method of Parallel Reaction Monitoring-Parallel Accumulation–Serial Fragmentation (prm-PASEF) was implemented and adapted. It was demonstrated that the new prm-PASEF method utilized in the new generation timsTOF Pro mass spectrometer can be effectively used for targeted absolute quantitative proteomics with a high level of specificity and sensitivity.

It has been demonstrated that the combination of absolute quantitative proteomics technologies with machine learning is a highly accurate prognostic tool for assessing lethal outcomes in patients with COVID-19 when analyzing blood samples obtained at the time of patient admission to the hospital. Together with the Research Institute of Pulmonology, for the first time such an analysis was also carried out for samples of frozen whole blood. A method has been developed to assess the severity of patients with COVID-19 and predict fatal cases using the proposed panel of 13 proteins.

A prototype of a domestic kit has been created for the simultaneous determination of the concentration of 270 proteins in various types of blood samples (blood plasma, frozen blood, dried blood spot - DBS), which allows for comparative measurement of the concentrations of selected proteins with adequate accuracy. This “ready-to-use” prototype kit is comparable in performance to two existing commercial kits on the market for measuring 100-270 blood proteins (BAK 270 - MRM Proteomics, Canada and PQ100 - Biognosis, Switzerland).

Methods for quantitative multiplex determination of proteins have been developed, and adapted for the use for dried blood spot (DBS) samples. Together with the Institute of Biomedical Problems of the Russian Academy of Sciences, DBS samples collected from Russian cosmonauts during a long space flight (from 6 months to 1 year) were studied, and unique data were obtained in the field of proteomics of extreme states. Potential protein biomarkers of gravity-induced post-flight changes in cosmonauts have been identified.

A method for detecting the SARS CoV-2 virus in epithelial smears from the nasopharynx, based on mass spectrometric detection of the viral N-protein, has been developed and tested. The method allows reliable detection of the virus even in patients with a low viral load. Based on the results of the work, a patent for the invention was obtained.

In the field of oncology, in collaboration with the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov was developed a highly accurate classifier (sensitivity 91%, specificity 89%, AUC = 0.92), which made it possible to distinguish between metastatic and non-metastatic breast cancer (BC) - the classifier is based on logistic regression and serum levels of 11 proteins.

Particularly noteworthy is the developed method for diagnosing Alzheimer's disease (AD) based on detected biomarker signatures and AI and machine learning algorithms, which allows assessing the risk of developing the disease, including at an early stage. An important aspect of the proposed methodology is the ability to predict the development of AD in patients with mild cognitive decline syndrome. The proposed method can reduce the cost of diagnostics (especially compared to PET), and also ensures minimal invasiveness of research (especially compared to cerebrospinal fluid analysis), and significantly expands the possibilities of using the method for primary large-scale screening. In 2023, the method was successfully tested and validated at the Psychiatric Clinical Hospital No. 1 named after. N.A. Alekseev, Moscow. In 2023, the team received a patent for the invention and registered a computer program for identifying the most significant panel of blood proteins for assessing the risk of developing AD (RU 2023611275 dated January 18, 2023).

The main results of the work were presented at leading international scientific events and articles were published in peer-reviewed journals, including first quartile publications - Q1 (Anal Chem, MCP, IJMS, Frontiers physiology, Molecules, etc.).

Implementation of research results:

• Large-scale (more than 1000 patients) contractual clinical studies were carried out commissioned by the ANO "Moscow Center for Innovative Technologies in Healthcare" of the Department of Health, together with the State Budgetary Institution of Healthcare of the State Clinical Hospital named after. I.V. Davydovsky to assess the proteomic composition of blood plasma samples and extracellular vesicles for patients with cardiovascular and oncological diseases, and proposed potential markers for further validation.

• The technology for assessing the risk of developing Alzheimer's disease by analyzing the proteome of blood plasma in 2023 was successfully tested and validated at the Psychiatric Clinical Hospital No. 1 named after. N.A. Alekseev, Moscow.

Organizational and infrastructural changes:

In collaboration with the mass spectrometry laboratory, a new structural division of Skoltech was created - the Project Center for Advanced Mass Spectrometric Technologies under the leadership of Professor E.N. Nikolaev.

Education and personnel occupational retraining:

• Two training courses for Skoltech master's and postgraduate students in the Life Sciences programs have been created and implemented: 1) Biomedical mass spectrometry; 2) Omics technologies.
• 4 master's and 2 candidate's dissertations have been prepared and defended.
• Trainings are being conducted for Skoltech students and postgraduate students on the basics of quantitative proteomics

Cooperation:

• National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V. I. Kulakov of the Ministry of Health of the Russian Federation.
• Institute of Biomedical Problems of the Russian Academy of Sciences
• FSBI "Research Institute of Pulmonology" FMBA of Russia, Moscow
• Psychiatric Clinical Hospital No. 1 named after. N.A. Alekseev, Moscow.
• ANO "Moscow Center for Innovative Technologies in Healthcare" of the Department of Health, Moscow
• State Budgetary Institution of Healthcare of the City Clinical Hospital named after. I.V. Davydovsky
• University of Sharjah, UAE