Irina A. Shagina

Pirogov Russian National Research Medical University

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Dmitriy M. Chudakov

Skolkovo Institute of Science and Technology

Dmitry A. Shagin

Pirogov Russian National Research Medical University

ГВ

Г. В. Шаронов

Pirogov Russian National Research Medical University

Sergey Lukyanov

Pirogov Russian National Research Medical University

Olga V. Britanova

Institute of Bioorganic Chemistry

Maria A. Turchaninova

Pirogov Russian National Research Medical University

Dmitriy B. Staroverov

Pirogov Russian National Research Medical University

Ekaterina A. Bryushkova

Lomonosov Moscow State University

Dmitry V Komarov

Federal Medical-Biological Agency

Sofia V Krasik

Skolkovo Institute of Science and Technology

Cooperative Institutions

Institute of Bioorganic Chemistry

Pirogov Russian National Research Medical University

Ministry of Health of the Russian Federation

Russian Academy of Sciences

Lomonosov Moscow State University

Institute of Bioorganic Chemistry

Skolkovo Institute of Science and Technology

Privolzhsky Research Medical University

National Research Center for Hematology Russian Academy of Medical Sciences

Moscow State University

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Preparation of prokaryotic cDNA for full-scale transcriptome analysis

Russian Journal of Bioorganic Chemistry (2011)

Е. А. Богданова Irina A. Shagina Yurii G. Yanushevich Laura L. Vagner Sergey Lukyanov

Suppression subtractive hybridization

10.1134/s1068162011060045

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Citations (4)

Application of nonsense-mediated primer exclusion (NOPE) for preparation of unique molecular barcoded libraries

BMC Genomics (2017)

Dmitry A. Shagin Maria A. Turchaninova Irina A. Shagina Mikhail Shugay Andrew R. Zaretsky

Recently we proposed efficient method to exclude undesirable primers at any stage of amplification reaction, here termed NOPE (NOnsense-mediated Primer Exclusion). According to this method, added oligonucleotide overlapping with the 3'-end of unwanted amplification primer (NOPE oligo) simultaneously provides a template for its elongation. This elongation disrupts specificity of unwanted primer, preventing its further participation in PCR. The suggested approach allows to rationally manage the course of PCR reactions in order to facilitate analysis of complex DNA mixtures as well as to perform multistage PCR bypassing intermediate purification steps.Here we apply NOPE method to DNA library preparation for the high-throughput sequencing (HTS) with the PCR-based introduction of unique molecular identifiers (UMI). We show that NOPE oligo efficiently neutralizes UMI-containing oligonucleotides after introduction of UMI into sample DNA molecules, thus allowing to proceed with further amplification steps without purification and associated loss of starting material. At the same time, NOPE oligo does not affect the efficiency of target PCR amplification.We describe a simple, robust and cheap modification of UMI-labeled HTS libraries preparation procedure, that allows to bypass purification step and thus to preserve starting material which may be limited, e.g. circulating tumor DNA, circulating fetal DNA, or small amounts of isolated cells of interest. Furthermore, demonstrated simplicity and robustness of NOPE method should make it popular in various PCR protocols.

Primer (cosmetics)

Primer dimer

10.1186/s12864-017-3815-2

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Citations (2)

Systematic evaluation of intratumoral and peripheral BCR repertoires in three cancers

eLife (2024)

Sofia V Krasik Ekaterina A. Bryushkova Г. В. Шаронов Daria S Myalik Elizaveta V Shurganova

The current understanding of humoral immune response in cancer patients suggests that tumors may be infiltrated with diffuse B cells of extra-tumoral origin or may develop organized lymphoid structures, where somatic hypermutation and antigen-driven selection occur locally. These processes are believed to be significantly influenced by the tumor microenvironment through secretory factors and biased cell-cell interactions. To explore the manifestation of this influence, we used deep unbiased immunoglobulin profiling and systematically characterized the relationships between B cells in circulation, draining lymph nodes (draining LNs), and tumors in 14 patients with three human cancers. We demonstrated that draining LNs are differentially involved in the interaction with the tumor site, and that significant heterogeneity exists even between different parts of a single lymph node (LN). Next, we confirmed and elaborated upon previous observations regarding intratumoral immunoglobulin heterogeneity. We identified B cell receptor (BCR) clonotypes that were expanded in tumors relative to draining LNs and blood and observed that these tumor-expanded clonotypes were less hypermutated than non-expanded (ubiquitous) clonotypes. Furthermore, we observed a shift in the properties of complementarity-determining region 3 of the BCR heavy chain (CDR-H3) towards less mature and less specific BCR repertoire in tumor-infiltrating B-cells compared to circulating B-cells, which may indicate less stringent control for antibody-producing B cell development in tumor microenvironment (TME). In addition, we found repertoire-level evidence that B-cells may be selected according to their CDR-H3 physicochemical properties before they activate somatic hypermutation (SHM). Altogether, our work outlines a broad picture of the differences in the tumor BCR repertoire relative to non-tumor tissues and points to the unexpected features of the SHM process.

10.7554/elife.89506

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Decoding the fine-scale structure of a breast cancer genome and transcriptome

Genome Research (2006)

Stanislav Volik Benjamin J. Raphael Guiqing Huang Michael R. Stratton Graham Bignel

A comprehensive understanding of cancer is predicated upon knowledge of the structure of malignant genomes underlying its many variant forms and the molecular mechanisms giving rise to them. It is well established that solid tumor genomes accumulate a large number of genome rearrangements during tumorigenesis. End Sequence Profiling (ESP) maps and clones genome breakpoints associated with all types of genome rearrangements elucidating the structural organization of tumor genomes. Here we extend the ESP methodology in several directions using the breast cancer cell line MCF-7. First, targeted ESP is applied to multiple amplified loci, revealing a complex process of rearrangement and coamplification in these regions reminiscent of breakage/fusion/bridge cycles. Second, genome breakpoints identified by ESP are confirmed using a combination of DNA sequencing and PCR. Third, in vitro functional studies assign biological function to a rearranged tumor BAC clone, demonstrating that it encodes antiapoptotic activity. Finally, ESP is extended to the transcriptome identifying four novel fusion transcripts and providing evidence that expression of fusion genes may be common in tumors. These results demonstrate the distinct advantages of ESP including: (1) the ability to detect all types of rearrangements and copy number changes; (2) straightforward integration of ESP data with the annotated genome sequence; (3) immortalization of the genome; (4) ability to generate tumor-specific reagents for in vitro and in vivo functional studies. Given these properties, ESP could play an important role in a tumor genome project.

10.1101/gr.4247306

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Citations (56)

Sort-Seq: immune repertoire-based scRNA-Seq systematization

bioRxiv (Cold Spring Harbor Laboratory) (2023)

Valeriia Kriukova Daniil K. Lukyanov Irina A. Shagina Г. В. Шаронов Ksenia R. Lupyr

Abstract The functional programs chosen by B and T cell clones fundamentally determine the architecture of immune response to distinct challenges. Advances in scRNA-Seq have improved our understanding of the diversity and stability of these programs, but it has proven difficult to link this information with known lymphocyte subsets. Here, we introduce Sort-Seq, an immune repertoire-based method that allows exact positioning of phenotypically defined lymphocyte subsets within scRNA-Seq data. Sort-Seq outperformed CITE-Seq for accurate mapping of the classical CD4 + T helper (Th) cell subsets (Th1, Th1-17, Th17, Th22, Th2a, Th2, and Treg), offering a more powerful approach to the surface phenotype-based scRNA-Seq classification of adaptive lymphocyte subpopulations. Using integrated scRNA-Seq, Sort-Seq, and CITE-Seq data from 122 donors, we provide a comprehensive Th cell scRNA-Seq reference map. Exploration of this dataset revealed the low plasticity and extreme sustainability of the Th17, Th22, Th2, and Th2a cell programs over years. We also develop Cultivation-based Antigen-specific T cell identificatoR in Replicates (CultivAToRR), which identified >80 SARS-CoV-2-specific CD4 + TCRβ clonotypes in a single donor across a wide frequency range. We complemented these results with frequency- based capturing of COVID-19-responsive clonotypes and screening against known SARS-CoV-2- specific TCRs. Positioning within the annotated scRNA-Seq map revealed functional subtypes of Th cell clones involved in primary and secondary responses against SARS-CoV-2. The ability to capture low-frequency antigen-specific T cell clones in combination with Sort-Seq-based scRNA- Seq annotation creates an integral pipeline that links challenge-responsive clones with their exact functional subtypes, providing a solid foundation for investigating T cell roles in healthy and pathological immune responses and vaccine development.

10.1101/2023.10.24.563704

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Citations (1)

Untitled ItemNaïve Regulatory T Cell Subset Is Altered in X-Linked Agammaglobulinemia (part2)

Figshare (2021)

Pavel V. Shelyakin Ksenia R. Lupyr Evgeny S. Egorov И.А. Кофиади Dmitriy B. Staroverov

Clonosets from 3 cell subsets (CD4+ mature naive, CD4+ RTE, naive Treg) sorted from blood of XLA and healthy (old and young) donors. Total RNA was isolated using the RNeasy mini kit (Qiagen) according to the manufacturer’s instructions. In all experiments described here, cDNA libraries were obtained using 5’-RACE with unique molecular identifiers (UMI) using Human TCR profiling kit (MiLaboratory LLC). Libraries were sequenced on Illumina NextSeq 500 using 300 cycle reagent kit, paired-end 150 + 150 nt mode. Clonotypes were inferred from reads using MIGEC (UMI threshold = 2) + MIXCR + VDJTOOLS

X-linked agammaglobulinemia

10.6084/m9.figshare.15131340.v2

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Citations (0)

Naïve Regulatory T Cell Subset Is Altered in X-Linked Agammaglobulinemia (part2)

Figshare (2021)

Pavel V. Shelyakin Ksenia R. Lupyr Evgeny S. Egorov И.А. Кофиади Dmitriy B. Staroverov

X-linked agammaglobulinemia

10.6084/m9.figshare.15131340

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Citations (0)

Genetic screening among children with congenital and early childhood hearing loss

Markova Tg MV V Nekrasovan Irina A. Shagina A V Poliakov

Prevalence of mutations of genes of connexin 26, connexin 30 and mitochondrial DNA was studied among children with congenital and early childhood hearing loss. Screening with available methods of DNA diagnosis was conducted in some specialized schools. It was found that genetic disorders among children with congenital and early childhood hearing loss are rather frequent. Genetic consulting of parents with normal hearing carrying abnormal gene can help avoid birth of deaf children.

Congenital hearing loss

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Interferon signature in the development of SLE: molecular mechanisms, approaches to diagnosis and treatment

Bulletin of Russian State Medical University (2024)

TO Nakonechnaya Irina A. Shagina M.Y. Myshkin ZYu Mutovina E.V. Ryazantseva

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by inflammation of connective tissue and damage to various organs, including joints, skin, kidneys and heart. The disease has a significant gender predisposition and is more common in women. The pathogenesis of SLE is based on a violation of immunological tolerance, accompanied by activation of B lymphocytes and the production of autoantibodies. Recent advances in basic research have significantly deepened the understanding of the immunopathogenetic mechanisms of SLE, which justifies the use of new pharmacotherapeutic approaches. These approaches involve the use of biological drugs aimed at blocking the activity of type I interferon (IFN) or its receptors. The article discusses the molecular mechanisms of activation of the interferon response in SLE, modern methods for diagnosing the interferon signature, and new approaches to treatment aimed at blocking the interferon pathway. The possible role of the interferon signature in the stratification of SLE patients is also discussed. Such stratification will make it possible to more effective select treatment regimens taking into account the individual characteristics of the immune response of each patient. This may increase the effectiveness of treatment, reduce the likelihood of side effects and improve the prognosis for patients with SLE.

Pathogenesis

10.24075/brsmu.2024.027

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Citations (0)

The use of duplex-specific crab nuclease for rapid analysis of single-nucleotide polymorphisms and the detection of DNA targets in complex PCR products

Russian Journal of Bioorganic Chemistry (2011)

Irina A. Shagina Е. А. Богданова I. M. Altshuler Sergey Lukyanov Dmitry A. Shagin

Nuclease

Duplex (building)

Cloning (programming)

clone (Java method)

10.1134/s1068162011040121

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Citations (2)