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 symposiumFunctional study of potential regulatory SNPs (rs590352, rs11542583, rs3829202, rs78317230, rs2072580, rs4796672)

Functional study of potential regulatory SNPs (rs590352, rs11542583, rs3829202, rs78317230, rs2072580, rs4796672)

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Poster (download)

[pdf-embedder url=”https://bgrssb.icgbio.ru/wp-content/uploads/2020/07/524.pdf”]
Arina Degtyareva1, Elena Leberfarb2, Ilya Brusentsov3, Tatiana Kuzina4, Tatiana Merkulova5
1ICG SB RAS, degtyareva_rso@mail.ru
2ICG SB RAS, lieberfarb@bionet.nsc.ru
3ICG SB RAS, brusentsovi@gmail.com
4NSU, t.kuzina@g.nsu.ru
5ICG SB RAS, merkulova@bionet.nsc.ru

In a previous study using a new bioinformatic approach based on Chip-Seq data with antibodies against various transcription factors and histone modifications, ChiA-PET, RNA-seq and ICGC data, 32 potentially regulatory single -nucleotide polymorphisms (rSNPs) were associated with colorectal cancer. In this study, a functional analysis of 6 of these polymorphisms was performed using EMSA and the luciferase reporter system. These nucleotide substitutions have been shown to alter the binding of nuclear extract proteins and influence the expression of the reporter gene.

 

Systems Biology and Biomedicine symposiumDNA damage to nervous tissue due to lead intoxication combined with glucose loading

DNA damage to nervous tissue due to lead intoxication combined with glucose loading

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Yakimova Natalya Leonidovna1, Andreeva Elizaveta Sergeevna2, Buinova Ekaterina Vladimirovna3
1Estern-Siberian Institute of Medical and Ecological Research, Angarsk, Russia, ynl-77@list.ru
2Estern-Siberian Institute of Medical and Ecological Research, Angarsk, Russia, liza.2995@mail.ru
3Estern-Siberian Institute of Medical and Ecological Research, Angarsk, Russia, byuncat@mail.ru

The influence of heavy metals on various organs and systems is known. Diabetes disorders are also well understood. The component contribution of glucose loading was manifested in an increase in genotoxic lesions of nerve cells caused by lead intoxication. DNA damage in the tail of nerve cell comets after exposure to lead and glucose loading increased to 52.86 (13.16–73.34) percent compared to 25.28 (12.24–54.79) percent of people poisoned by lead. In animals exposed to lead and glucose, brain cells with high DNA damage in the tail of comets dominated the brain, 62.77 (54.68-70.87) percent of the cells were apoptosis-positive compared to 48.42 (38, 37-58.47) percent rats treated with lead acetate without glucose load.

Systems Biology and Biomedicine symposiumInfluence of the Immobilized Subtilisins on Perfomance Indicators of the Rat Heart in Experiment

Influence of the Immobilized Subtilisins on Perfomance Indicators of the Rat Heart in Experiment

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Pavel Madonov1, Roman Knyazev2, Konstantin Ershov3
1Department of Experimental Pharamology Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences Novosibirsk, Russian Federation Department of Pharmacology, Clinical Pharmacology and Evidence-Based Medicine Novosibirsk State Medical University Novosibirsk, Russia Federation, Pmadonov@yandex.ru
2Research Institute of Biochemistry – a branch of the Federal Research Center for Fundamental and Translational Medicine Department of Pharmacology, Clinical Pharmacology and Evidence-Based Medicine Novosibirsk State Medical University Novosibirsk, Russian Federation, Knjazev_roman@mail.ru
3Department of Pharmacology, Clinical Pharmacology and Evidence-Based Medicine Novosibirsk State Medical University, Novosibirsk, Russian Federation, Ershov_k@bk.ru

Abstract The immobilized subtilisins are bacterial proteinases with a high thrombolytic activity, capable of improving peripheral blood circulation by dissolving the blood clot and reducing manifestations of endothelial dysfunction. This article presents the materials of the effect of immobilized subtilisins on performance heart indicators in the experiment. В The action of these proteinases was studied on a model of isolated rat heart according to Langendorff. Indicators of heart rate (HR), pressure developed by the left ventricle (LVP), heart efficiency (HE) were selected for registration. It was shown when adding the immobilized subtilisins, an increase of the left ventricular contraction force and a decrease in a heart rate were observed. The results indicate that immobilized subtilisins have positive inotropic and negative chronotropic effects.

Systems Biology and Biomedicine symposiumThe Siberian multimodal brain tumor image segmentation dataset (SBT)

The Siberian multimodal brain tumor image segmentation dataset (SBT)

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[pdf-embedder url=”https://bgrssb.icgbio.ru/wp-content/uploads/2020/07/514.pdf”]
Sergey Golushko1, Mikhail Amelin2, Bair Tuchinov3, Evgeniya Amelina4, Nikolay Tolstokulakov5, Evgeniy Pavlovskiy6, Vladimir Groza7
1Novosibirsk State University, s.k.golushko@gmail.com
2FSBI \”Federal Neurosurgical Center\”, amelin81@gmail.com
3Novosibirsk State University, bairts@gmail.com
4Novosibirsk State University, amelina.evgenia@gmail.com
5Novosibirsk State University, n.tolstokulakov@g.nsu.ru
6Novosibirsk State University, pavlovskiy@post.nsu.ru
7Median Technologies, vladimir.groza@gmail.com

Automatic brain tumor segmentation from CT or MRI scans is one of the crucial problems among other directions and domains where daily clinical workflow requires to put a lot of efforts while studying patients with various pathologies.In this paper, we report the results of the research project \”Brain Tumor Segmentation\” organized in conjunction with the Federal Neurosurgical Center. Several state-of-the-art tumor segmentation algorithms were applied to a set of 100 MRI scans of meningioma, neurinoma and glioma patients – manually annotated by up to three raters – and to 100 comparable scans obtained using the automated tumor multi-region segmentation. Quantitative evaluations revealed a considerable agreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 85-90\\%). We found that different algorithms worked best for different sub-regions, but no single algorithm ranked in the top for all subregions simultaneously.

Systems Biology and Biomedicine symposiumGenetic association of the rs4680 COMT and rs1044396 CHRNA4 with internet addiction in Siberian adolescents

Genetic association of the rs4680 COMT and rs1044396 CHRNA4 with internet addiction in Siberian adolescents

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Marina Smolnikova1, Sergey Tereshchenko2
1Laboratory of cell-molecular physiology and pathology Scientific Research Institute of Medical Problems of the North FRC KSC SB RAS Krasnoyarsk, Russia, smarinv@yandex.ru
2Clinical department somatic and mental health of children Scientific Research Institute of Medical Problems of the North FRC KSC SB RAS Krasnoyarsk, Russia, legise@mail.ru

Abstract As the use of the Internet grows, the issue of the pathological and problematic Internet use (PIU) as well as online games has been relevant. Research related to a family history of temperament and mental disorders has rapidly been developing. Having the genetic component of developing Internet addiction was shown by twin studies using various populations, however, to date, the specific genes involved in the mechanisms of such heritability are not exactly identified. Materials: Genotyping of rs4680 COMT and rs1044396 CHRNA4 in 345 adolescents with different severity of internet addiction (tested with Chen Internet Addiction Scale) were analyzed. Results: The predominant allelic variant rs4680*G COMT in Khakass teenagers regardless of the severity of Internet addiction compared with Russian teenagers have been shown. It is important that some significant differences have also been observed between Russian PIU (45.5%) and Khakas PIU (63.8%) (OR 0.47, p = 0.024). We revealed that rs1044396 CC genotype prevalence progressively increase with IA severity: AIU group (n=179) – 19.0%, MIU group (n=82) – 32.9%, and PIU group (n=84) – 34.5%. The CC variant of rs1044396 CHRNA4 showed significantly higher anxiety scores as compared with carriers of T-allele. Our results correspond to similar results in the adult in another populations and are pilot in Russia; they are important for understanding the pathogenesis of IA at an early stage of addiction formation.

Systems Biology and Biomedicine symposiumChemotherapeutic agent cisplatin suppresses stabilin-1-mediated clearance of EGF by tumor-associated macrophage

Chemotherapeutic agent cisplatin suppresses stabilin-1-mediated clearance of EGF by tumor-associated macrophage

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[pdf-embedder url=”https://bgrssb.icgbio.ru/wp-content/uploads/2020/07/476.pdf”]
Irina Larionova1, Elena Kazakova2, Artyem Kiselev3, Marina Patysheva4, Julia Kzhyshkowska5
1National Research Tomsk State University, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia, larionova0903irina@mail.ru
2National Research Tomsk State University Tomsk, Russia, kazakova.e.o@mail.ru
3Almazov National Medical Research Centre, Saint Petersburg, Russia, artem.kiselyov@gmail.com
4National Research Tomsk State University, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia, starin5@ya.ru
5National Research Tomsk State University, Tomsk, Russia, German Red Cross Blood Service Baden-WГјrttemberg – Hessen, Mannheim, Germany, julia.kzhyshkowska@googlemail.com

In this study we have demonstrated the suppression of receptor-mediated clearance of tumor-supportive factors EGF by cisplatin in tumor-associated macrophages. These results may be useful for the determining of the mechanisms of the interaction of TAMs and chemotherapy and the mechanism of macrophage-mediated tumor chemoresistance.

Systems Biology and Biomedicine symposiumThyroid dysfunction is associated with osteoporosis in patients with Hodgkin’s lymphoma

Thyroid dysfunction is associated with osteoporosis in patients with Hodgkin’s lymphoma

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Poster (download)

[pdf-embedder url=”https://bgrssb.icgbio.ru/wp-content/uploads/2020/07/228.pdf”]
Mariya S. Voytko1, Vadim V. Klimontov2, Tatyana I. Pospelova3, Olga N. Fazullina4, Alexander I. Autenshlyus5
1Novosibirsk State Medical University, voytko.marie@yandex.ru
2Research Institute of Clinical and Experimental Lymphology, klimontov@mail.ru
3Novosibirsk State Medical University, post_gem@mail.ru
4Research Institute of Clinical and Experimental Lymphology, fazullina@ngs.ru
5Novosibirsk State Medical University, post_gem@mail.ru

Background and Aim: Radiation therapy (RT) is a cornerstone component of the treatment for many patients with Hodgkin\’s lymphoma (HL). Current treatment options for HL are mostly effective, but may have a negative pronounced damaging effect on some organs. Specifically, RT can induce thyroid dysfunction and decrease in bone mineral density (BMD). The aim of the study was to assess the prevalence of thyroid dysfunction in HL survivors and estimate its effect on BMD.

Methods: The study included 160 patients with HL, from 18 to 65 years of age (median 42 years), observed in Hematology Center of Novosibirsk. The disease was staged according to the Ann Arbor staging system; 71 patients had limited stage (I-II) and 84 patients had advanced stage disease (stage III to IV). All subjects received first-line regimens. Neck and supraclavicular RT was performed in 96 (60%) individuals; the total dose was 30 Gy in 84 patients and 36 Gy in 11 ones. Thyroid hormones were measured by enzyme immunoassays. The BMD was assessed by dual-energy X-ray absorptiometry. Statistical data processing was performed using STATISTICA (StatSoft, Inc., USA).
Results: The changes in thyroid function were revealed in 40 (25%) patients. Among them, primary hypothyroidism was verified in 30 subjects, including 18 individuals with subclinical hypothyroidism. Ten patients had central hypothyroidism. Thirty two patients had neck and supraclavicular RT in their anamnesis. In this subgroup, hypothyroidism was observed in 22 subjects with total focal dose of 30 Gy and in 8 subjects with the total focal dose of 36 Gy. The decrease in BMD was revealed in 76 HL subjects (47.5%), 43 of them diagnosed as having osteoporosis. The decline in BMD was more frequent in patients with hypothyroidism as compared to those without (П‡2=13.4, СЂ<0.001).
Conclusion: Hypothyroidism is associated with decrease in BMD in patients with HL.

Systems Biology and Biomedicine symposiumGlucose variability in subjects with type 1 diabetes: the relationships with non-enzymatic glycation, albuminuria and renal function

Glucose variability in subjects with type 1 diabetes: the relationships with non-enzymatic glycation, albuminuria and renal function

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[pdf-embedder url=”https://bgrssb.icgbio.ru/wp-content/uploads/2020/07/464.pdf”]
Vadim V Klimontov1, Julia Рђ Semenova2, Alla K. Vigel3
1Laboratory of Endocrinology Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL – Branch of IC&G SB RAS), klimontov@mail.ru
2Laboratory of Endocrinology Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL – Branch of IC&G SB RAS), ekmxtyjr@yandex.ru
3Laboratory of Endocrinology Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL – Branch of IC&G SB RAS), endo-kray@mail.ru

Background and aim: Recent studies recognized increased glucose variability (GV) as an independent risk factor for chronic kidney disease (CKD) in diabetes. We aimed to assess the relationships between GV parameters, serum levels of glycation products, albuminuria and renal function in subjects with type 1 diabetes (T1D) at early and advanced stages of CKD.

Materials and Methods: We observed 148 T1D patients, including 95 individuals with CKD C1-C2 and 53 subjects had CKD C3-5. Time in range (TIR: 70-180 mg/dl), time below range (TBR), time above range (TAR) and a panel of GV parameters were derived from continuous glucose monitoring (CGM). Serum levels of 1,5-anhydroglucitol (1,5-AG), glycated albumin (GA) and advanced glycation end products (AGEs) were determined by ELISA and compared to control (20 healthy subjects).

Results: In patients with CKD C1-C2, HbA1c levels correlated positively with mean monitored glucose, TAR, MAGE, LI, HBGI, CONGA, MAG and M-value. In patients with more advanced CKD stages these relationships were lost. Concentrations of GA and AGEs were elevated significantly in subjects with diabetes as compared to control (p=0.004 and p<0.0001, respectively). The levels of 1,5-AG were reduced (p<0.0001), reflecting increase in GV. The levels of GA, but not AGEs, were associated negatively with 1,5-AG concentration. In CKD C1-C2 group, the estimated glomerular filtration rate (eGFR) showed inverse relationships with TBR and LBGI. Oppositely, in CKD C3-C5 patients eGFR correlated negatively with mean glucose, TAR, MAGE, CONGA, HBGI and M-value and some GV parameters. In both groups albuminuria was associated positively with AGEs, GA, HbA1c, mean glucose, TAR, and GV indices.

Conclusions: The results demonstrate different patterns of relationships between eGFR and GV parameters in patients with T1D at early and advanced CKD stages. In these patients, enhanced GV may contribute to albuminuria through acceleration of non-enzymatic glycation processes.
Systems Biology and Biomedicine symposiumInvestigation of the Allergenic Properties of the Interferon-Lambda 1, Pegylated by Electron-Beam Method

Investigation of the Allergenic Properties of the Interferon-Lambda 1, Pegylated by Electron-Beam Method

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[pdf-embedder url=”https://bgrssb.icgbio.ru/wp-content/uploads/2020/07/461.pdf”]
Nikolai Kikhtenko1, Larisa Oleynik2
1Novosibirsk State Medical University, dr.kikhtenko@gmail.com
2Research Institute of Clinical and Experimental Lymphology – Branch of IC&G SB RAS, larisaoleynik81@gmail.com

The development of effective antiviral drugs for use in ophthalmic practice is an urgent task of modern medicine. Type III interferons have similar functions with well-known type I interferons, that is they have antiviral, antitumor and immunomodulating activities. However, their receptors are expressed primarily on epithelial barrier cells, such as mucous membranes. In this regard, type III interferons have less systemic side effects when used for therapeutic purposes. However, interferons are protein molecules, which mean that they are practically not absorbed from gastrointestinal tract, therefore, they need parenteral administration, which reduces patient compliance.

It was shown that electron-beam pegylation increases the solubility of the original substances, reduces immunogenic properties, and also increases the oral bioavailability of proteins up to 20%. However, a change of the molecule structure can significantly change both pharmacokinetic and pharmacodynamic properties.

In this work the allergenic properties of interferon-l1, pegylated by electron beam method, were investigated in the systemic anaphylaxis reaction in guinea pigs, and in the active cutaneous anaphylaxis reaction and the conjunctival test in mice.

Thus, it was found that PEG-IFN-О»1, obtained by the electron beam method, generally does not have allergenic properties when used in a therapeutic dose or in ten-fold higher dose, in the conditions of the experiments. This creates the prerequisites for the development of a drug based on PEG-IFN-О»1 for the treatment of viral infections of the ocular surface, which requires further experiments to establish its effectiveness.

Systems Biology and Biomedicine symposiumClinical and metabolic parameters associated with time in ranges and glucose variability in patients with type 2 diabetes treated with insulin

Clinical and metabolic parameters associated with time in ranges and glucose variability in patients with type 2 diabetes treated with insulin

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[pdf-embedder url=”https://bgrssb.icgbio.ru/wp-content/uploads/2020/07/458.pdf”]
Julia F. Semenova1, Maksim V. Dashkin2, Olga N. Fazullina3
1Laboratory of Endocrinology Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences(RICEL – Branch of IC&G SB RAS) Novosibirsk, Russia, ekmxtyjr@yandex.ru
2Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL – Branch of IC&G SB RAS) Novosibirsk, Russia, mdashkin@invitro.ru
3Laboratory of Endocrinology Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences(RICEL – Branch of IC&G SB RAS) Novosibirsk, Russia, fazullina@ngs.ru

Background and aim: Continuous glucose monitoring (CGM) provides an excellent opportunity for in-depth assessment of glycemic control and glucose variability (GV) in diabetic subjects. The aim of our study was to determine the clinical and metabolic parameters associated with non-targeted time in range (TIR) increased GV in patients with type 2 diabetes (T2D) treated with insulin.В Materials and Methods: One hundred and thirty six insulin-treated patients with T2D were included. Real-time or blinded CGM was performed using Medtronic CGM devices. The TIR and Mean Amplitude of Glucose Excursion (MAGE) were estimated. The advance glycation end-products (AGEs) levels were measured in blood serum by ELISA.В Results: Patients with non-targeted TIR (>70%) had higher glycated hemoglobin HbA1c, triglycerides and proteinuria as compared to those with targeted TIR. Urinary albumin-to-creatinine ratio tended to be higher in patients with non-targeted TIR also. Patients with higher MAGE (>4.5 mmol/l) demonstrated lower levels of triglycerides and uric acid and increased AGEs levels as compared to those with MAGE <4.5 mmol/l.В Conclusions: In T2D subjects, non-targeted TIR is associated with hypertriglyceridemia and proteinuria, meantime, increased MAGE is related to lower serum levels of triglycerides and uric acid and higher levels of AGEs.