Seminars 2022/2023

12.01.2022 [online] Non-canonical transcripts of HSV-1

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Speaker: Fedorov Alexander, junior researcher

The eighty known open reading frames (ORFs) of HSV-1 have been extensively studied over decades. However, the actual number of RNA transcribed from the viral genome is much higher and amounts to several hundred. Some of them encode previously undescribed but experimentally confirmed proteins. Others are probably just 5' elongated isoforms. These and many other facts about the biological role of non-canonical HSV-1 transcripts will be discussed in detail during the report.

09.02.2022 [online] Role of ICP27 in cells infected with HSV-1

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Speaker: Fedorov Alexander, junior researcher

Virus infections, including HSV-1, cause massive disruption of transcription termination (DOTT) in host cells. However, the underlying mechanisms of this process remain a mystery. It has been experimentally shown that ICP27, one of 80 HSV-1 proteins, is able to induce DOTT by direct binding to the 3' end processing factors of some host RNAs. At the same time, ICP27 plays an important role in the correct termination of viral RNA transcription. These and other facts will be described in detail during the report.

16.03.2022 [online] Interaction between tumor cells and its microenvironment: detection of ligand-receptor pairs

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Speaker: Osintseva Ekaterina, Master's student of «Data Analysis in Biology and Medicine» program

The study of the heterogeneity of the tumor microenvironment and the interaction of its cells with each other and with the tumor may help to reveal the mechanisms by which the tumor avoids the immune response. Understanding these mechanisms is of value in the first place for the development of various methods of immunotherapy.

Using the CellChat package for 8 scRNA-seq samples of metastases in the brain parenchyma, pairs of interactions between different cell types were found according to the ligand-receptor principle. Primary analysis showed in all samples the presence of interactions between cells through the MIF ligand, in particular, this interaction was observed between metastatic cells and cells of the immune system. Literature review has shown that such interactions can lead to tumor progression and immunosuppression.

16.04.2022 [online] Analysis of cell death pathways in populations of tumor cells and its microenvironment

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Speaker: Osintseva Ekaterina, Master's student of «Data Analysis in Biology and Medicine» program

Today, the term "tumor microenvironment" refers to the totality of components of a solid tumor, including its vasculature, tumor-associated fibroblasts, various immune cells, and extracellular matrix. The study of cell death pathways in the context of malignant neoplasms is important for two reasons: firstly, the activation of cell death programs in tumor cells can be used as a cancer therapy technique, and secondly, the "fratricide" of various immune cell populations can affect the progression of the disease and the avoidance of the immune response by the tumor.

This report will highlight the results of the analysis of the activity of cell death pathways in 8 scRNA-seq samples of metastases in the brain parenchyma.

25.05.2022 [online] The role of flipons and miRNAs in determining promoters at early stages of development

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Speaker: Pavlov Fedor, PhD student

There are several points of view on the mechanisms by which gene regulation is carried out. The results of computational experiments suggest that in these processes there is a deep connection between the mechanisms of RNA and DNA. The report presents data supporting a model in which flipons open binding sites for miRNAs, leading to the creation of bivalent promoters early in development. The results of computational experiments are presented, which indicate a clear predominance of certain groups of flipons as the most preferred candidates for binding to regions of conserved miRNAs.

22.06.2022 [online] Prediction of Z-DNA regions in the human and mouse genomes

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Speaker: Beknazarov Nazar, junior researcher

The role of Z-DNA in cellular processes is known, and over time, an increasing involvement of this DNA structure in the regulation of expression, the immune response, and many other processes has been discovered. Therefore, the study and prediction of Z-DNA regions in various organisms has become of current interest. The report presents experiments on the prediction of Z-DNA by machine learning models trained on experimental labeling and analysis of the predictions obtained, followed by a comparison of the findings obtained on different organisms.

13.07.2022 [online] RNA editing landscape in Alzheimer's disease

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Speaker: Konovalov Dmitry, trainee researcher

Alzheimer's disease is one of the most common neurodegenerative diseases. Research into disease-specific RNA editing may shed light on new methods to combat it. The report will describe the currently available data on RNA editing, the ADeditome database, and the possible role of flipons in the regulation of neurodegenerative processes.

24.08.2022 [online] Comparison of the quality of various methods of domain adaptation in bioinformatics problems

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Speaker: Latyshev Pavel, PhD student

A report was presented on a comparative study of 9 methods of domain adaptation: ADDA, AFN, CDAN, DAN, DANN, JAN, MCC, MCD, MDD. These methods have been applied to various histone marks and transcription factors on the human, mouse, nematode, drosophila, and yeast genomes. Comparative tables with quality metrics on various tasks were shown and analyzed.

21.09.2022 [online] LGP2 and its role in the regulation of IFN-response in cells with inactivated ADAR1

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Speaker: Fedorov Alexander, junior researcher

RNA editing by adenosine deaminase ADAR1 prevents the cellular immune response to endogenous RNAs. In cells with inactivated ADAR1, unedited self-RNAs form base-pair structures that resemble viral RNAs and inadvertently activate the MDA5 receptor, leading to a type I IFN-response. However, MDA5 is not the only receptor required to induce an immune response. Another essential receptor is LGP2.

12.10.2022 [online] Transcription factor Aire

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Speaker: Pavlov Fedor, PhD student

Aire (autoimmune regulator) is a protein that plays a significant role in the regulatory processes of the genome due to its active involvement in the formation of tolerance of the immune system. To date, it is known that Aire is responsible for the regulation of thousands of genes, but there is no understanding of the specific mechanisms through which this regulation is carried out. The report discusses the interaction analysis of Aire and four sets of Z-DNA regions that were obtained using computational and experimental methods. The results of bulk RNA-seq analysis of Aire-KO data are presented, as a result of which a target group of Aire-activated genes in the mouse organism is isolated.

26.10.2022 [online] Cis-regulatory elements and Z-flipons

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Speaker: Konovalov Dmitry, trainee researcher

Cis-regulatory elements are regions of nucleic acids that regulate the expression of genes located on the same molecule. Flipons located in these regions can regulate gene expression by changing the secondary structure of DNA. This report will present the results of the analysis of the localization of Z-flipons and describe the main methods of conducting: determining the coordinates of cis-regulatory elements, studying the association of traits, and determining the genes and processes potentially regulated by this mechanism.

16.11.2022 [online] Investigation of the DANN domain adaptation method for predicting G-quadruplexes

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Speaker: Latyshev Pavel, PhD student

The report presented the use of domain adaptation for machine learning models trained on one organism for reuse on other organisms. The quality of adaptation was studied on the G4-ChIP-Seq and G4-Seq datasets on human and mouse DNA.

16.01.2023 [online] Graph Neural Networks for Predicting DNA Secondary Structures

Speaker: Artyom Voytetsky, trainee researcher

The report presented three modules that carry out training, testing various graph networks based on the prepared data, and also draws additional graphs (ROC-, PR- and F1 score curves).

20.02.2023 [online] Z-DNA segment prediction pipeline

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Speaker: Anna Danilova, trainee researcher

The report has been updated by a program that is a pipeline for learning and runs a Transformer that predicts Z-DNA regions.

13.03.2023 [online] Inverted repeats in the eukaryotic genome: structure and functions

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Speaker: Aleksandr Fedorov, Junior Researcher

A significant, and often overwhelming, portion of eukaryotic genomes is composed of repetitive sequences. DNA repeats are extremely diverse in nature and often do not have a defined biological function. However, among the variety of eukaryotic repeats, inverted repeats (IRs) stand out separately. Based on a series of experiments, we know that some of them tend to form cruciform structures in DNA, which are involved in replication, transcriptional regulation, and chromatin organization. Additionally, during transcription, IR can form long segments of double-stranded RNA, which are critical for innate immune response and can further be processed into small interfering RNAs with various functions. These and other details of IR biology will be discussed during the presentation.

03.04.2023 [online] Mathematical modeling of a spatial structure of proteins

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Speaker: Ignatov A.D.

Modeling of the spatial structure of proteins is a computationally demanding task. It has a large number of degrees of freedom and hence an extremely large number of variables are involved. One can use coarse-grained protein models in order to simplify the geometry of protein structure. A coarse-grained HP-model based on hydrophobicity and polarity of protein side chains would be in the spotlight. It could be used to reduce the problem of predicting a protein conformation to a problem of combinatorial optimization, in which the objective function is the number of contacts between H-monomers of a protein chain.

A number of techniques have been proposed to accelerate the prediction of the spatial structure of proteins in the HP-model. A completely new algorithm is developed to create both the densest hydrophobic cores and cores with a limit on the maximum number of contacts between H-monomers. New ways of filtering hydrophobic cores and new sets of restrictions for protein placement in a simulated hydrophobic core have been proposed.

11.04.2023 [offline] Investigation of the DANN domain adaptation method for predicting G-quadruplexes

10 Pokrovsky Boulevard, Room D504

Speakers: B.V. Chernyshev – Head of Scientific and Educational Center for Neuro-Cognitive Research (MEG Center) MSUPE, E.V. Orekhova – Lead Researcher of MEG Center

In this seminar a unique method for studying brain activity in real time and with a high spatial resolution is introduced. MEG Center is a research facility focused on neurophysiological mechanisms of training, memory, perception, and decision-making, as well as autism spectrum disorders and related neuropsychiatric disorders.

12.04.2023 [online] Detection of flipons using Kas-seq to identify single-stranded DNA

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Speaker: Dmitry Konovalov, trainee researcher

The report discusses the results of an analysis of the Kas-seq experiment performed on several human and mouse cell lines. This method uses ketoxal to identify sections of single-stranded DNA. Such areas can signal the presence of flipons. Special attention was paid to promoter regions. The results of computational experiments show that Kas-seq is consistent with other experimental data and predictions of machine learning models for determining flipons.

13.04.2023 [online] Development of a pipeline for investigation of Z-RNA

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Speaker: Danilova Anna, trainee researcher

Analyzing RNA secondary structure is required when studying a role of Z-RNA in the genome. Both structure itself and ZH-score value are important. Since it is required to examine thousands of different RNA structures, manual analysis with the use of existing solutions, such as RNA-Fold, becomes time-consuming. Besides, existing solutions do not feature ZH-score calculation. That is why the idea of creating a custom pipeline, which would be able to find RNA secondary structures of input sequences, calculate ZH-score of these structures, and visualize them.

14.04.2023 [online] Plasma B cell-associated genes predicts better response to immunotherapy in metastatic but not primary melanoma tumors

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Speaker: Grigory Puzanov, Researcher

In recent years, a number of studies show the role of B cells in predicting response to immunotherapy. However, this role varies depending on the type of tumor. The report describes the signature of plasma B-cells found by analyzing single-cell sequencing data of brain metastases for various types of tumors (melanoma, lung cancer, breast cancer, ovarian cancer). For each sample in which B cells were present, a cell subtype was found with specific expression of the ZBP1, DERL3, and TNFRSF17 genes. Further, TCGA data confirms the association of these gene expression with plasma cells and reveals an association with better survival for melanoma metastases.

17.04.2023 [offline] Non-cooperative foundation of cooperative actions: the generalized Nash Program

Pokrovsky boulevard, 11, R406

Speaker: Dmitry Levando, PhD in economics

We demonstrate how to construct coalition structures with any number of coalitions from non-cooperative actions of individual agents. The approach expands the traditional non-cooperative game of Nash for the field of non-cooperative coalition formation. The suggested game embeds a coalition structure formation mechanism, and has two outcomes: an allocation of players over coalitions and payoffs for every player. An individual strategy is a tuple, a coalition structure and a strategy for it. A player has a set of strategies for every coalition structure.  Coalition structures are described by the Young diagrams. A (social) mechanism transforms a set of all individual strategies into some final one, with explicit allocation of players over coalitions.  The mechanism has an enforcement power to eliminate conflicts of individual choices.  A final coalition structure has a set of individual payoffs. As usual, every game has an equilibrium in mixed strategies, which is different from results of cooperative game theory. The game of Nash is a partial case of the presented model. We demonstrate how to construct a non-cooperative stability criteria for the strong Nash equilibrium.