International Multiconference “Bioinformatics of Genome Regulation and Structure\Systems Biology”

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Systems Biology and Biomedicine symposium

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Systems Biology and Biomedicine symposiumIL1b T-31C and VEGFРђ C+936T SNPs may be used as prognostic markers of rheumatoid arthritis treatment inefficiency

IL1b T-31C and VEGFРђ C+936T SNPs may be used as prognostic markers of rheumatoid arthritis treatment inefficiency

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[pdf-embedder url=”https://bgrssb.icgbio.ru/wp-content/uploads/2020/07/239.pdf”]
Vitaly Omelchenko1, Elena Letyagina2, Alla Shevchenko3, Yuliya Kurochkina4, Anna Akimova5, Maxim Korolev6
1Research Institute of Clinical and Experimental LymСЂhology – Branch of the Institute of Cytology and Genetics, v.o.omelchenko@gmail.com
2Research Institute of Clinical and Experimental LymСЂhology – Branch of the Institute of Cytology and Genetics, elena_letyagina@list.ru
3Research Institute of Clinical and Experimental LymСЂhology – Branch of the Institute of Cytology and Genetics, shalla64@mail.ru
4Research Institute of Clinical and Experimental LymСЂhology – Branch of the Institute of Cytology and Genetics, juli_k@bk.ru
5Research Institute of Clinical and Experimental LymСЂhology – Branch of the Institute of Cytology and Genetics, calor844@gmail.com
6Research Institute of Clinical and Experimental LymСЂhology – Branch of the Institute of Cytology and Genetics, kormax@bk.ru

Objectives: The aim of our study was to analyze the association between some SNPs and treatment of rheumatoid arthritis with biological drugs.

Patients and methods: We studied 368 Russian patients with rheumatoid arthritis. All of them were treated in accordance with the standard recommendations. Fifty seven patient received biological disease-modifying antirheumatic drugs. Single nucleotide polymorphisms (TNFО± C-863A, TNFО± G-308A, TNFО± G-238A, IL1ОІ T-31РЎ, IL4 РЎ-590T, IL6 G-174C, IL10 A-1082G, IL10 РЎ-592Рђ, VEGFA C+936T, VEGFA C-2578A) were determined by restriction fragment length polymorphism analysis of PCR-amplified fragments (PCR-RFLP) or RT-PCR.

Results: The IL1β T-31C and VEGFA C+936T SNPs were association with bDMARDs treatment. Homozygotes IL1b -31CC and VEGFА +936 CC were more frequently in bDMARDs group compare with patients without bDMARDs (28.1% vs 17.1%, p=0.044 and 80.4% vs 66.6%, p=0.041). Other polymorphisms didn’t demonstrate any significant differences.

Conclusions: Our data suggest, that IL1ОІ T-31C and VEGFA C+936T SNPs can be used as part of a comprehensive assessment of the prognosis of the treatment effectiveness.

Systems Biology and Biomedicine symposiumWhy we need more complex gene diagnostic: the case study of exome from patient with congenital glaucoma

Why we need more complex gene diagnostic: the case study of exome from patient with congenital glaucoma

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Dinara Ivanoshchuk1, Mikhail Voevoda2, Natalia Konovalova3, Konstantin Gunbin4
1ICG SB RAS, Novosibirsk, Russia, dinara@bionet.nsc.ru
2ICG SB RAS, Novosibirsk, Russia, voevoda@bionet.nsc.ru
3TSMA, Tumen, Russia, doctork@bk.ru
4ICG SB RAS, Novosibirsk, Russia, genkvg@bionet.nsc.ru

Usually, a detailed analysis of well-known diseases-related genes for the presence of pathogenic variants does not give any meaningful result, despite the good agreement between the patient’s diagnosis and the available data on the mutations manifestation in these genes. This study, we try to disentangle such a cases using gene network aware exome analysis and variants prioritization.

Systems Biology and Biomedicine symposiumSemi-quantitative analysis of serum proteome in patients with bipolar disorder

Semi-quantitative analysis of serum proteome in patients with bipolar disorder

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Poster (download)

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Seregin Alexander Alexandrovich1, Smirnova Lyudmila Pavlovna2, Simutkin German Gennadievich3
1Mental Health Research Institute Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk, Russia, apocalips1991@mail.ru
2Mental Health Research Institute Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk, Russia, lpsmirnova@yandex.ru
3Mental Health Research Institute Tomsk National Research Medical Center of the Russian Academy of Sciences Tomsk, Russia, ggsimutkin@gmail.com

The work analyzed the protein spectrum of blood serum of 45 with bipolar disorder. Protein recruitment in BD was mainly associated with the immune response, regulation of transport processes through the cell membrane and cellular communication, the development of neurons and oligodendrocytes, and cell growth. Cadherin-5 and vascular endothelial growth factor receptor 1 are a marker of endothelial dysfunction. The detection of these proteins suggests the presence of endothelial dysfunction in the pathogenesis of BD. The detection of myelin 1 transcription factor and the literature data on the effect of mutations in the MYT1L gene on the risk of major depressive disorder suggest the MYT1 protein as a potential BD biomarker. The results may help to discover new pathways associated BD.

Systems Biology and Biomedicine symposiumOpportunities of Trabecular Bone Score to Evaluate Ankylosing Spondilitis Structural Progression in Young Male Patients

Opportunities of Trabecular Bone Score to Evaluate Ankylosing Spondilitis Structural Progression in Young Male Patients

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Kolpakov Konstantin1, Korolev Maxim2, Letyagina Elena3
1Laboratory of Connective Tissue Disease, RICEL – Branch of ICG SB RAS Novosibirsk, Russian Federation, elmad95@mail.ru
2Laboratory of Connective Tissue Disease, RICEL – Branch of ICG SB RAS Novosibirsk, Russian Federation, kormax@bk.ru
3Laboratory of Connective Tissue Disease, RICEL – Branch of ICG SB RAS Novosibirsk, Russian Federation, elena_letyagina@list.ru

Ankylosing spondylitis (AS) is a chronic progressive systemic inflammatory disease, with a primary lesion of the spine and sacroiliac joints characterized by simultaneously running processes of osteogenesis (syndesmophytes) and osteoresorption (osteoporosis). The aim of this work is to investigate trabecular bone score (TBS) correlation with signs of structural progression of AS in the males before 50. Fourteen AS male patients before 50 without osteoporosis are included in investigation. The relationships between TBS, the Kellgren sacroiliitis stage, and BMD indices in different parts of the skeleton were studied using Spearman correlation analysis. A strong negative correlation was found between TBS and the X-ray stage of Kellgren sacroiliitis (r = -0.69; p <0.05) in men before 50 with AS. BMD does not reflect the degree of structural disturbances and the risks of spinal fractures in men before 50 with AS in the absence of other causes of secondary osteoporosis.

Systems Biology and Biomedicine symposiumImmunoglobulins with proteolytic activity as a biomarker of impaired humoral immune system in schizophrenia

Immunoglobulins with proteolytic activity as a biomarker of impaired humoral immune system in schizophrenia

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Evgeny Ermakov1, Valentina Buneva2, Georgy Nevinsky3
1ICBFM SB RAS, Novosibirsk, Russia; NSU, Novosibirsk, Russia, evgeny_ermakov@mail.ru
2ICBFM SB RAS, Novosibirsk, Russia; NSU, Novosibirsk, Russia, buneva@niboch.nsc.ru
3ICBFM SB RAS, Novosibirsk, Russia; NSU, Novosibirsk, Russia, nevinsky@niboch.nsc.com

Schizophrenia is known to be associated not only with imbalance in the neurotransmitter systems but also with immune system dysregulation. In this work, we found that pure polyclonal IgG preparations of patients with schizophrenia possess histone hydrolyzing proteolytic activity. The presence of proteolytic activity of IgGs is evidence of impaired humoral immune system in schizophrenia, which can be used as a biomarker for immunophenotyping of patients.

Systems Biology and Biomedicine symposiumMechanisms of ischemic kidney tolerance in young and senescence-accelerated rats exposured to ischemic preconditioning or calorie restriction

Mechanisms of ischemic kidney tolerance in young and senescence-accelerated rats exposured to ischemic preconditioning or calorie restriction

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Egor Plotnikov1, Nadezda Andrianova2, Stanislovas Jankauskas3, Irina Pevzner4, Ljubava Zorova5, Vasily Popkov6, Denis Silachev7, Natalia Kolosova8, Dmitry Zorov9
1A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, plotnikov@belozersky.msu.ru
2A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, andnadya12@gmail.com
3A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, jankauskas.ss@gmail.com
4A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, irinapevzner@mail.ru
5A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, lju_2003@list.ru
6A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, popkov.vas@gmail.com
7A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, silachev_dn@belozersky.msu.ru
8Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), kolosova@bionet.nsc.ru
9A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, zorov@belozersky.msu.ru

Dietary restriction and ischemic preconditioning are the most efficient approaches ameliorating the severity of different pathological conditions. We investigated the protective potential of long-term calorie restriction and short ischemic preconditioning protocol in the model of acute kidney injury (AKI) in young Wistar and OXYS rats. In young rats, ischemic preconditioning, which consists of 4 cycles of ischemia and reperfusion alleviated kidney injury caused by 40-min ischemia. However, 6-month-old OXYS rats having signs of premature aging lost their ability to protect the ischemic kidney by IPC. However, CR of OXYS rats led to a significant decrease in creatinine and BUN levels after kidney ischemia, indicating significant protection.

Systems Biology and Biomedicine symposiumProteomic Analysis of Extracellular Vesicles Produced by Placental Mesenchymal Stem Cells

Proteomic Analysis of Extracellular Vesicles Produced by Placental Mesenchymal Stem Cells

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Anastasia Khutornenko1, Anastasia Zharikova2, Vasily Popkov3, Sergey Kovalchuk4, Kirill Goryunov5, Yulia Shevtsova6, Egor Plotnikov7, Dmitry Zorov8, Denis Silachev9
1Laboratory of Cell Technologies, Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia, bioingenier@gmail.com
2Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia, azharikova89@gmail.com
3The A.N. Belozersky Institute Of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia, popkov.vas@gmail.com
4Laboratory of Bioinformatic methods for Combinatorial Chemistry and Biology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia, xerx222@gmail.com
5Laboratory of Cell Technologies, Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia, kirishgor@gmail.com
6Laboratory of Cell Technologies, Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia, yulshevtsova@yandex.ru
7A.N. Belozersky Institute of Physico-Chemical Biology; Research Center of Obstetrics, Gynecology and Perinatology, Moscow, Russia, plotnikov@belozersky.msu.ru
8A.N. Belozersky Institute of Physico-Chemical Biology; Reserch Center of Obstetrics, Gynecology and Perinatology, Moscow, Russia, zorov@belozersky.msu.ru
9A.N. Belozersky Institute of Physico-Chemical Biology; Research Center of Obstetrics, Gynecology and Perinatology, Moscow, Russia, d_silachev@oparina4.ru

Mesenchymal stem/stromal cells (MSCs) have therapeutic potential in many pathological conditions, that is explained mostly by their paracrine action. MSCs secrete extracellular vesicles (EVs) packed with proteins, DNA, RNA and lipids. One of the easily accessible and reach sources of MSCs is placenta. In order to reveal possible pathways, by which EVs produced by placenta-derived MSCs (EVs-PMSC) could realize their therapeutic potential we conducted proteomic analysis of EVs-PMSC and subsequent bioinformatic analysis of identified proteins using Reactome pathway database. Identified peptides were mapped to 2093 proteins. Among the 2093 proteins, 972 proteins were identified in at least four LC-MS/MS analyses out of eight. According to Reactome the most significant ‘top three’ 1st level pathways for detected EVs-PMSC proteins were ‘Cellular responses to external stimuli’; ‘Immune system’; ‘Developmental biology’. Some of the most enriched pathways in the group ‘Cellular responses to external stimuli’ were: ‘Response of EIF2AK4 (GCN2) to amino acid deficiency’; ‘Cellular response to hypoxia’; ‘Detoxification of Reactive Oxygen Species’. Some of the most enriched pathways in the group ‘Immune System’ were: ‘Class I MHC mediated antigen processing & presentation’; ‘Neutrophil degranulation’; ‘Interferon Signaling’. The most enriched pathway in the group ‘Developmental biology’ was ‘Axon guidance’. Thus far, concerning most enriched pathways EVs-PMSC proteome is expected to: 1) provide protection against stress (amino acid deficiency, hypoxia, ROS) to the damaged tissues; 2) possess immunomodulation properties; 3) facilitate axon guidance. The result (the top list of enriched pathways) leads to the notion that EVs-PMSC could be effective in terms of neuroprotection.

Systems Biology and Biomedicine symposiumThe effect of lithium carbonate on angiogenesis of hepatocellular carcinoma-29

The effect of lithium carbonate on angiogenesis of hepatocellular carcinoma-29

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Viktoriia Makarova1, Nataliya Bgatova2, Iuliia Taskaeva3
1Laboratory of ultrastructural research, Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, shedina_vika@mail.ru
2Laboratory of ultrastructural research, Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, n_bgatova@ngs.ru
3Laboratory of ultrastructural research, Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, inabrite@yandex.ru

Гепатоцеллюлярная карцинома является одной из самых агрессивных опухолей человека с высокой распространенностью и смертностью. В то же время существует проблема устойчивости ГЦК к стандартной терапии. Поиск лекарств, блокирующих рост и метастазирование опухоли, является актуальным. Имеются данные о противоопухолевых свойствах карбоната лития. Целью нашего исследования было определить влияние лития на развитие и структуру кровеносных сосудов экспериментальной гепатоцеллюлярной карциномы-29 (G-29). Исследование было выполнено на самцах мышей CBA. Клетки гепатокарциномы-29 использовали для индукции опухолевого процесса. Изучали экспрессию эндотелиального маркера кровеносных сосудов (CD-31) и ультраструктурную организацию опухолевых сосудов эндотелиальных клеток. Было показано, что карбонат лития уменьшает объемную плотность кровеносных сосудов G-29. Ультраструктурный анализ опухолевых сосудов выявил нетипичный характер их строения. Стенки сосудов были выстланы как эндотелиальными, так и опухолевыми клетками.

Systems Biology and Biomedicine symposiumComputational prediction of miRNA binding sites in mRNA of colorectal cancer candidate genes

Computational prediction of miRNA binding sites in mRNA of colorectal cancer candidate genes

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Aigul Akimniyazova1
1SRI of Biology and Biotechnology problems, al-Farabi Kazakh National University, akimniyazova@gmail.com

The identification of causative miRNAs in colorectal cancer is unclear due to a lack of understanding of how specific miRNAs affect biological pathways and consequences of disease development. The miRNA is a class of nano-sized non-coding RNAs that regulate many mRNAs, and mRNA can be related to many miRNAs, which make them suitable for diagnosis purposes. Therefore it is required to identify candidate genes of colorectal cancer and to what extent they can interact with miRNA. To determine the important miRNAs biding sites in genes, involved in the development of colorectal cancer, there were used the MirTarget program. The paper presents the results of studying the characteristics of the interaction of miRNAs with mRNAs of 135 candidate genes involved in the development of colorectal cancer. The binding sites of 446 miRNAs have in 113 mRNA of genes at 5\’UTR, CDS, and 3\’UTR. Found miRNA binding sites with overlapped nucleotide sequences (clusters). The research results are useful for the development of methods for early diagnosis of this disease.

Systems Biology and Biomedicine symposiumExpression of Glycogen Synthase Kinase 3ОІ in Nephrotic Syndrome

Expression of Glycogen Synthase Kinase 3ОІ in Nephrotic Syndrome

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Sepideh Zununi Vahed1, Elham Ahmadian2, Mohammadreza Ardalan3
1Kidney Research Center Tabriz University of Medical Sciences Tabriz, Iran, sepide.zununi@gmail.com
2Kidney Research Center Tabriz University of Medical Sciences Tabriz, Iran, ahmadian.elham@yahoo.com
3Kidney Research Center Tabriz University of Medical Sciences Tabriz, Iran, ardalan34@yahoo.com

Abstract Aberrant expression of glycogen synthase kinase-3 (GSK-3ОІ) in kidney cells has a harmful role in podocyte injury. In this work, we found that dysregulated levels of GSK-3ОІ may be involved in the pathogenesis of nephrotic syndrome, renal disease with proteinuria, with different etiology.

Keywords Nephrotic syndrome, Proteinuria, Membranous glomerulonephritis, Focal Segmental Glomerulosclerosis, GSK-3ОІ.

В В В В В В В В В В В В В В В В В В В В В В В В В В В В  I.В В В В  Motivation and aim

A.В В В  Motivation

Glycogen synthase kinase-3 (GSK-3) is a conserved multi-functional serine/threonine kinase that regulates various physiological processes, including gene expression, cell signaling [1], cellular proliferation, apoptosis, and intracellular communication. A detailed understanding of the GSK-3ОІ function and its expression in several pathological conditions will help the clinic manage different kidney diseases.

B.В В В  Aim.

Given the role of GSK-3ОІ in the podocytes injury [2,3], we evaluate its expression levels in PBMCs samples of patients with NS.

В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В  II.В В В  Methods

The expression levels of GSK-3ОІ was evaluated in peripheral blood mononuclear cells (PBMCs) of cases with the most common types of nephrotic syndrome (NS); MGN (membranous glomerulonephritis) and FSGS (focal segmental glomerulosclerosis) using real-time PCR. Sixty cases (30 FSGS and 30 MGN) were included based on the strict criteria. The results compared with healthy controls (n=24). The receiver operating characteristic (ROC) curve analysis was used for evaluating the potential of GSK-3ОІ in discriminating cases from controls.

В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В В  III.В В  Results

There were statistically significant increases in GSK-3ОІ expression level in NS (P=0.002) and FSGS (P<0.001) groups when compared to controls; however, it was not significant in the MGN group (P= 0.137). The GSK-3ОІ level was also significantly higher in the FSGS group in comparison to the MGN group. ROC curve analysis approved a diagnostic power of GSK-3ОІ in discriminating patients from healthy controls (AUC: 0.72, P= 0.002) with high sensitivity and specificity.