vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJGB-23-90vavilov-3977Research ArticleСИСТЕМНАЯ КОМПЬЮТЕРНАЯ БИОЛОГИЯSYSTEMS COMPUTATIONAL BIOLOGYМолекулярно-генетические пути регуляции вирусом гепатита С экспрессии клеточных факторов PREB и PLA2G4C, играющих важную роль для репликации вирусаMolecular-genetic pathways of hepatitis C virus regulation of the expression of cellular factors PREB and PLA2G4C, which play an important role in virus replicationМищенкоЕ. Л.MishchenkoE. L.

Новосибирск

Novosibirsk

https://orcid.org/0009-0005-1844-7921МакароваА. А.MakarovaA. A.

Новосибирск

Novosibirsk

https://orcid.org/0000-0003-2158-3252АнтроповаЕ. А.AntropovaE. A.

Новосибирск

Novosibirsk

ВензельА. С.VenzelA. S.

Новосибирск

Novosibirsk

https://orcid.org/0000-0002-0005-9155ИванисенкоТ. В.IvanisenkoT. V.

Новосибирск

Novosibirsk

https://orcid.org/0000-0001-9433-8341ДеменковП. С.DemenkovP. S.

Новосибирск

Novosibirsk

https://orcid.org/0000-0002-1859-4631ИванисенкоВ. А.IvanisenkoV. A.

Новосибирск

Novosibirsk

salix@bionet.nsc.ruФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Курчатовский геномный центр ИЦиГ СО РАНРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Kurchatov Genomic Center of ICG SB RASRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Курчатовский геномный центр ИЦиГ СО РАН; Новосибирский национальный исследовательский государственный университетРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Kurchatov Genomic Center of ICG SB RAS; Novosibirsk State UniversityRussian Federation202311122023277776783Copyright © Мищенко Е.Л., Макарова А.А., Антропова Е.А., Вензель А.С., Иванисенко Т.В., Деменков П.С., Иванисенко В.А., 20232023Мищенко Е.Л., Макарова А.А., Антропова Е.А., Вензель А.С., Иванисенко Т.В., Деменков П.С., Иванисенко В.А.Mishchenko E.L., Makarova A.A., Antropova E.A., Venzel A.S., Ivanisenko T.V., Demenkov P.S., Ivanisenko V.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/3977

В репликации генома вируса гепатита С (ВГС) участвуют как вирусные, так и хозяйские белки. Терапевтические подходы, основанные на подавлении активности неструктурных вирусных белков NS3, NS5A, NS5B, проходят клинические испытания разных уровней. Однако быстрые мутационные процессы вирусного генома и приобретение лекарственной устойчивости остаются одними из главных препятствий в борьбе с ВГС. 

Идентификация и исследование клеточных факторов, участвующих в репликации РНК ВГС, а также регуляция вирусом их экспрессии важны для понимания механизмов репликации вируса и разработки эффективных подходов противовирусной терапии. Известно, что белок PREB, связывающий регуляторный элемент пролактина, и цитозольная фосфолипаза А2 гамма (PLA2G4C) играют важную роль в формировании платформ репликации РНК ВГС, а также в функционировании вирусной репликазы. Экспрессия генов PREB и PLA2G4C значительно увеличена в присутствии ВГС, но механизмы ее регуляции вирусными белками до сих пор не изучены. В данной работе с применением технологии текст-майнинга, реализованной в программно-информационной системе ANDSystem, реконструированы генные сети регуляции экспрессии генов человека PREB и PLA2G4C белками ВГС. На основании анализа генных сетей мы выдвинули гипотезы о регуляторных эффектах белков ВГС на функции хозяйских факторов в результате белок-белковых взаимодействий. Среди вирусных белков наибольшее количество регуляторных связей выявлено у вирусной протеазы NS3. Предположительно NS3 в результате белок-белкового взаимодействия подавляет активность транскрипционного фактора NOTCH1, что обусловливает активацию экспрессии PREB и PLA2G4C. Анализ генных сетей и данных о дифференциальной экспрессии генов в присутствии ВГС позволил нам также выдвинуть гипотезы о регуляции вирусом экспрессии транскрипционных факторов, сайты связывания которых находятся в районах генов PREB и PLA2G4C, и действии этих транскрипционных факторов на регуляцию транскрипции PREB и PLA2G4C. Полученные результаты могут быть использованы при планировании исследований по изучению молекулярно-генетических механизмов взаимодействия вирус–хозяин и поиска потенциальных мишеней для разработки лекарств против ВГС.

The participants of Hepatitis C virus (HCV) replication are both viral and host proteins. Therapeutic approaches based on activity inhibition of viral non-structural proteins NS3, NS5A, and NS5B are undergoing clinical trials. However, rapid mutation processes in the viral genome and acquisition of drug resistance to the existing drugs remain the main obstacles to fighting HCV. Identifying the host factors, exploring their role in HCV RNA replication, and studying viral effects on their expression is essential for understanding the mechanisms of viral replication and developing novel, effective curative approaches. It is known that the host factors PREB (prolactin regulatory element binding) and PLA2G4C (cytosolic phospholipase A2 gamma) are important for the functioning of the viral replicase complex and the formation of the platforms of HCV genome replication. The expression of PREB and PLA2G4C was significantly elevated in the presence of the HCV genome. However, the mechanisms of its regulation by HCV remain unknown. In this paper, using a text-mining technology provided by ANDSystem, we reconstructed and analyzed gene networks describing regulatory effects on the expression of PREB and PLA2G4C by HCV proteins. On the basis of the gene network analysis performed, we put forward hypotheses about the modulation of the host factors functions resulting from protein-protein interaction with HCV proteins. Among the viral proteins, NS3 showed the  greatest number of regulatory linkages. We assumed that NS3 could inhibit the function of host transcription factor (TF) NOTCH1 by protein-protein interaction, leading to upregulation of PREB and PLA2G4C. Analysis of the gene networks and data on differential gene expression in HCV-infected cells allowed us to hypothesize further how HCV could regulate the expression of TFs, the binding sites of which are localized within PREB and PLA2G4C gene regions. The results obtained can be used for planning studies of the molecular-genetic mechanisms of viral-host interaction and searching for potential targets for anti-HCV therapy.

вирус гепатита Срепликация генома ВГСрепликаза ВГСхозяйские факторыгенные сетифосфолипаза PLA2G4Cбелок PREBhepatitis C virusHCV gene replicationreplicase HCVhost factorsgene networksphospholipase PLA2G4CPREB proteinThis work is supported by the budget project No. FWNR-2022-0020.ReferencesAlam A., Hana Z., Jin Z., Suen K.C., Ma D. Surgery, neuroinflammation and cognitive impairment. EBioMedicine. 2018;37:547-556. DOI 10.1016/j.ebiom.2018.10.021Alam A., Hana Z., Jin Z., Suen K.C., Ma D. Surgery, neuroinflammation and cognitive impairment. EBioMedicine. 2018;37:547-556. DOI 10.1016/j.ebiom.2018.10.021Basov N.V., Rogachev A.D., Aleshkova M.A., Gaisler E.V., Sotnikova Y.S., Patrushev Y.V., Tolstikova T.G., Yarovaya O.I., Pokrovsky A.G., Salakhutdinov N.F. Global LC-MS/MS targeted metabolomics using a combination of HILIC and RP LC separation modes on an organic monolithic column based on 1-vinyl-1,2,4-triazole. Talanta. 2024;267:125168. DOI 10.1016/j.talanta.2023.125168Basov N.V., Rogachev A.D., Aleshkova M.A., Gaisler E.V., Sotnikova Y.S., Patrushev Y.V., Tolstikova T.G., Yarovaya O.I., Pokrovsky A.G., Salakhutdinov N.F. Global LC-MS/MS targeted metabolomics using a combination of HILIC and RP LC separation modes on an organic monolithic column based on 1-vinyl-1,2,4-triazole. Talanta. 2024;267:125168. DOI 10.1016/j.talanta.2023.125168Brown C.H. Delirium in the cardiac surgical intensive care unit. Curr. Opin. Anaesthesiol. 2014;27(2):117-122. DOI 10.1097/ACO.0000000000000061Brown C.H. Delirium in the cardiac surgical intensive care unit. Curr. Opin. Anaesthesiol. 2014;27(2):117-122. DOI 10.1097/ACO.0000000000000061Cerejeira J., Firmino H., Vaz-Serra A., Mukaetova-Ladinska E.B. The neuroinflammatory hypothesis of delirium. Acta Neuropathol. 2010; 119(6):737-775. DOI 10.1007/s00401-010-0674-1Cerejeira J., Firmino H., Vaz-Serra A., Mukaetova-Ladinska E.B. The neuroinflammatory hypothesis of delirium. Acta Neuropathol. 2010; 119(6):737-775. DOI 10.1007/s00401-010-0674-1Corre I., Guillonneau M., Paris F. Membrane signaling induced by high doses of ionizing radiation in the endothelial compartment. Relevance in radiation toxicity. Int. J. Mol. Sci. 2013;14(11):2267822696. DOI 10.3390/ijms141122678Corre I., Guillonneau M., Paris F. Membrane signaling induced by high doses of ionizing radiation in the endothelial compartment. Relevance in radiation toxicity. Int. J. Mol. Sci. 2013;14(11):2267822696. DOI 10.3390/ijms141122678Gao L., Taha R., Gauvin D., Othmen L.B., Wang Y., Blaise G. Postoperative cognitive dysfunction after cardiac surgery. Chest. 2005; 128(5):3664-3670. DOI 10.1378/chest.128.5.3664Gao L., Taha R., Gauvin D., Othmen L.B., Wang Y., Blaise G. Postoperative cognitive dysfunction after cardiac surgery. Chest. 2005; 128(5):3664-3670. DOI 10.1378/chest.128.5.3664García-Bueno B., Gassó P., MacDowell K.S., Callado L.F., Mas S., Bernardo M., Lafuente A., Meana J.J., Leza J.C. Evidence of activation of the Toll-like receptor-4 proinflammatory pathway in patients with schizophrenia. J. Psychiatry Neurosci. 2016a;41(3):E46-E55. DOI 10.1503/jpn.150195García-Bueno B., Gassó P., MacDowell K.S., Callado L.F., Mas S., Bernardo M., Lafuente A., Meana J.J., Leza J.C. Evidence of activation of the Toll-like receptor-4 proinflammatory pathway in patients with schizophrenia. J. Psychiatry Neurosci. 2016a;41(3):E46-E55. DOI 10.1503/jpn.150195García Bueno B., Caso J.R., Madrigal J.L., Leza J.C. Innate immune receptor Toll-like receptor 4 signalling in neuropsychiatric di sea ses. Neurosci. Biobehav. Rev. 2016b;64:134-147. DOI 10.1016/j.neubiorev.2016.02.013García Bueno B., Caso J.R., Madrigal J.L., Leza J.C. Innate immune receptor Toll-like receptor 4 signalling in neuropsychiatric di sea ses. Neurosci. Biobehav. Rev. 2016b;64:134-147. DOI 10.1016/j.neubiorev.2016.02.013Gottesman R.F., Grega M.A., Bailey M.M., Pham L.D., Zeger S.L., Baum gartner W.A., Selnes O.A., McKhann G.M. Delirium after coronary artery bypass graft surgery and late mortality. Ann. Neurol. 2010;67(3):338-344. DOI 10.1002/ana.21899Gottesman R.F., Grega M.A., Bailey M.M., Pham L.D., Zeger S.L., Baum gartner W.A., Selnes O.A., McKhann G.M. Delirium after coronary artery bypass graft surgery and late mortality. Ann. Neurol. 2010;67(3):338-344. DOI 10.1002/ana.21899Grassmé H., Cremesti A., Kolesnick R., Gulbins E. Ceramide-mediated clustering is required for CD95-DISC formation. Oncogene. 2003; 22(35):5457-5470. DOI 10.1038/sj.onc.1206540Grassmé H., Cremesti A., Kolesnick R., Gulbins E. Ceramide-mediated clustering is required for CD95-DISC formation. Oncogene. 2003; 22(35):5457-5470. DOI 10.1038/sj.onc.1206540Guo Y., Li Y., Zhang Y., Fang S., Xu X., Zhao A., Zhang J., Li J.V., Ma D., Jia W., Jiang W. Post-operative delirium associated with metabolic alterations following hemi-arthroplasty in older patients. Age Ageing. 2019;49(1):88-95. DOI 10.1093/ageing/afz132Guo Y., Li Y., Zhang Y., Fang S., Xu X., Zhao A., Zhang J., Li J.V., Ma D., Jia W., Jiang W. Post-operative delirium associated with metabolic alterations following hemi-arthroplasty in older patients. Age Ageing. 2019;49(1):88-95. DOI 10.1093/ageing/afz132Huang D.W., Sherman B.T., Lempicki R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protocols. 2009;4(1):44-57. DOI 10.1038/nprot.2008.211Huang D.W., Sherman B.T., Lempicki R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protocols. 2009;4(1):44-57. DOI 10.1038/nprot.2008.211Huang H., Han J., Li Y., Yang Y., Shen J., Fu Q., Chen Y. Early serum metabolism profile of post-operative delirium in elderly patients following cardiac surgery with cardiopulmonary bypass. Front. Aging Neurosci. 2022;14:857902. DOI 10.3389/fnagi.2022.857902Huang H., Han J., Li Y., Yang Y., Shen J., Fu Q., Chen Y. Early serum metabolism profile of post-operative delirium in elderly patients following cardiac surgery with cardiopulmonary bypass. Front. Aging Neurosci. 2022;14:857902. DOI 10.3389/fnagi.2022.857902Ivanisenko T.V., Saik O.V., Demenkov P.S., Ivanisenko N.V., Savostianov A.N., Ivanisenko V.A. ANDDigest: a new web-based module of ANDSystem for the search of knowledge in the scientific literature. BMC Bioinformatics. 2020;21(Suppl.11):228. DOI 10.1186/s12859-020-03557-8Ivanisenko T.V., Saik O.V., Demenkov P.S., Ivanisenko N.V., Savostianov A.N., Ivanisenko V.A. ANDDigest: a new web-based module of ANDSystem for the search of knowledge in the scientific literature. BMC Bioinformatics. 2020;21(Suppl.11):228. DOI 10.1186/s12859-020-03557-8Ivanisenko T.V., Demenkov P.S., Kolchanov N.A., Ivanisenko V.A. The new version of the ANDDigest tool with improved ai-based short names recognition. Int. J. Mol. Sci. 2022;23(23):14934. DOI 10.3390/ijms232314934Ivanisenko T.V., Demenkov P.S., Kolchanov N.A., Ivanisenko V.A. The new version of the ANDDigest tool with improved ai-based short names recognition. Int. J. Mol. Sci. 2022;23(23):14934. DOI 10.3390/ijms232314934Ivanisenko V.A., Saik O.V., Ivanisenko N.V., Tiys E.S., Ivanisen ko T.V., Demenkov P.S., Kolchanov N.A. ANDSystem: an Associative Network Discovery System for automated literature mining in the field of biology. BMC Sys. Biol. 2015;9(Suppl.2):S2. DOI 10.1186/1752-0509-9-S2-S2Ivanisenko V.A., Saik O.V., Ivanisenko N.V., Tiys E.S., Ivanisen ko T.V., Demenkov P.S., Kolchanov N.A. ANDSystem: an Associative Network Discovery System for automated literature mining in the field of biology. BMC Sys. Biol. 2015;9(Suppl.2):S2. DOI 10.1186/1752-0509-9-S2-S2Ivanisenko V.A., Demenkov P.S., Ivanisenko T.V., Mishchenko E.L., Saik O.V. A new version of the ANDSystem tool for automatic extraction of knowledge from scientific publications with expanded functionality for reconstruction of associative gene networks by considering tissue-specific gene expression. BMC Bioinformatics. 2019; 20(Suppl.1):34. DOI 10.1186/s12859-018-2567-6Ivanisenko V.A., Demenkov P.S., Ivanisenko T.V., Mishchenko E.L., Saik O.V. A new version of the ANDSystem tool for automatic extraction of knowledge from scientific publications with expanded functionality for reconstruction of associative gene networks by considering tissue-specific gene expression. BMC Bioinformatics. 2019; 20(Suppl.1):34. DOI 10.1186/s12859-018-2567-6Ivanisenko V.A., Gaisler E.V., Basov N.V., Rogachev A.D., Cheresiz S.V., Ivanisenko T.V., Demenkov P.S., Mishchenko E.L., Khripko O.P., Khripko Y.I., Voevoda S.M. Plasma metabolomics and gene regulatory networks analysis reveal the role of nonstructural SARSCoV-2 viral proteins in metabolic dysregulation in COVID-19 patients. Sci. Rep. 2022;12(1):19977. DOI 10.1038/s41598-022-24170-0Ivanisenko V.A., Gaisler E.V., Basov N.V., Rogachev A.D., Cheresiz S.V., Ivanisenko T.V., Demenkov P.S., Mishchenko E.L., Khripko O.P., Khripko Y.I., Voevoda S.M. Plasma metabolomics and gene regulatory networks analysis reveal the role of nonstructural SARSCoV-2 viral proteins in metabolic dysregulation in COVID-19 patients. Sci. Rep. 2022;12(1):19977. DOI 10.1038/s41598-022-24170-0Kanehisa M. The KEGG Database. In: ‘In silico’ Simulation of Biological Processes: Novartis Foundation Symposium. Chichester, UK: John Wiley & Sons, 2002;247:91-103. DOI 10.1002/0470857897.ch8Kanehisa M. The KEGG Database. In: ‘In silico’ Simulation of Biological Processes: Novartis Foundation Symposium. Chichester, UK: John Wiley & Sons, 2002;247:91-103. DOI 10.1002/0470857897.ch8Kanehisa M., Sato Y., Kawashima M. KEGG mapping tools for uncovering hidden features in biological data. Protein Sci. 2022;31(1): 47-53. DOI 10.1002/pro.4172Kanehisa M., Sato Y., Kawashima M. KEGG mapping tools for uncovering hidden features in biological data. Protein Sci. 2022;31(1): 47-53. DOI 10.1002/pro.4172Ke C., Pan C.W., Zhang Y., Zhu X., Zhang Y. Metabolomics facilitates the discovery of metabolic biomarkers and pathways for ischemic stroke: a systematic review. Metabolomics. 2019;15(12):152. DOI 10.1007/s11306-019-1615-1Ke C., Pan C.W., Zhang Y., Zhu X., Zhang Y. Metabolomics facilitates the discovery of metabolic biomarkers and pathways for ischemic stroke: a systematic review. Metabolomics. 2019;15(12):152. DOI 10.1007/s11306-019-1615-1Li K., Naviaux J.C., Bright A.T., Wang L., Naviaux R.K. A robust, single-injection method for targeted, broad-spectrum plasma metabolomics. Metabolomics. 2017;13(10):122. DOI 10.1007/s11306-017-1264-1Li K., Naviaux J.C., Bright A.T., Wang L., Naviaux R.K. A robust, single-injection method for targeted, broad-spectrum plasma metabolomics. Metabolomics. 2017;13(10):122. DOI 10.1007/s11306-017-1264-1Morimoto Y., Yoshimura M., Utada K., Setoyama K., Matsumoto M., Sakabe T. Prediction of postoperative delirium after abdominal surgery in the elderly. J. Anesth. 2009;23(1):51-56. DOI 10.1007/s00540-008-0688-1Morimoto Y., Yoshimura M., Utada K., Setoyama K., Matsumoto M., Sakabe T. Prediction of postoperative delirium after abdominal surgery in the elderly. J. Anesth. 2009;23(1):51-56. DOI 10.1007/s00540-008-0688-1Nosrati‐Oskouie M., Aghili‐Moghaddam N.S., Sathyapalan T., Sahebkar A. Impact of curcumin on fatty acid metabolism. Phytother. Res. 2021;35(9):4748-4762. DOI 10.1002/ptr.7105Nosrati‐Oskouie M., Aghili‐Moghaddam N.S., Sathyapalan T., Sahebkar A. Impact of curcumin on fatty acid metabolism. Phytother. Res. 2021;35(9):4748-4762. DOI 10.1002/ptr.7105O’Sullivan R., Inouye S.K., Meagher D. Delirium and depression: inter-relationship and clinical overlap in elderly people. Lancet Psychiatry. 2014;1(4):303-311. DOI 10.1016/S2215-0366(14)70281-0O’Sullivan R., Inouye S.K., Meagher D. Delirium and depression: inter-relationship and clinical overlap in elderly people. Lancet Psychiatry. 2014;1(4):303-311. DOI 10.1016/S2215-0366(14)70281-0Patrushev Y.V., Sotnikova Y.S., Sidel’nikov V.N. A monolithic column with a sorbent based on 1-vinyl-1,2,4-triazole for hydrophilic HPLC. Protect. Met. Phys. Chem. Surf. 2020;56(1):49-53. DOI 10.1134/s2070205119060248Patrushev Y.V., Sotnikova Y.S., Sidel’nikov V.N. A monolithic column with a sorbent based on 1-vinyl-1,2,4-triazole for hydrophilic HPLC. Protect. Met. Phys. Chem. Surf. 2020;56(1):49-53. DOI 10.1134/s2070205119060248Pisani M.A., Kong S.Y.J., Kasl S.V., Murphy T.E., Araujo K.L.B., Ness P.H.V. Days of delirium are associated with 1-year mortality in an older intensive care unit population. Am. J. Resp. Crit. Care Med. 2009;180(11):1092-1097. DOI 10.1164/rccm.200904-0537OCPisani M.A., Kong S.Y.J., Kasl S.V., Murphy T.E., Araujo K.L.B., Ness P.H.V. Days of delirium are associated with 1-year mortality in an older intensive care unit population. Am. J. Resp. Crit. Care Med. 2009;180(11):1092-1097. DOI 10.1164/rccm.200904-0537OCRogachev A.D., Alemasov N.A., Ivanisenko V.A., Ivanisenko N.V., Gai sler E.V., Oleshko O.S., Cheresiz S.V., Mishinov S.V., Stupak V.V., Pokrovsky A.G. Correlation of metabolic profiles of plasma and cerebrospinal fluid of high-grade glioma patients. Metabolites. 2021;11(3):133. DOI 10.3390/metabo11030133Rogachev A.D., Alemasov N.A., Ivanisenko V.A., Ivanisenko N.V., Gai sler E.V., Oleshko O.S., Cheresiz S.V., Mishinov S.V., Stupak V.V., Pokrovsky A.G. Correlation of metabolic profiles of plasma and cerebrospinal fluid of high-grade glioma patients. Metabolites. 2021;11(3):133. DOI 10.3390/metabo11030133Squiccimarro E., Labriola C., Malvindi P.G., Margari V., Guida P., Visicchio G., Kounakis G., Favale A., Dambruoso P., Mastrototaro G., Lorusso R., Paparella D. Prevalence and clinical impact of systemic inflammatory reaction after cardiac surgery. J. Cardiothorac. Vasc. Anesth. 2019;33(6):1682-1690. DOI 10.1053/j.jvca.2019.01.043Squiccimarro E., Labriola C., Malvindi P.G., Margari V., Guida P., Visicchio G., Kounakis G., Favale A., Dambruoso P., Mastrototaro G., Lorusso R., Paparella D. Prevalence and clinical impact of systemic inflammatory reaction after cardiac surgery. J. Cardiothorac. Vasc. Anesth. 2019;33(6):1682-1690. DOI 10.1053/j.jvca.2019.01.043Stafford-Smith M., Patel U.D., Phillips-Bute B.G., Shaw A.D., Swaminathan M. Acute kidney injury and chronic kidney disease after cardiac surgery. Adv. Chronic Kidney Dis. 2008;15(3):257-277. DOI 10.1053/j.ackd.2008.04.006Stafford-Smith M., Patel U.D., Phillips-Bute B.G., Shaw A.D., Swaminathan M. Acute kidney injury and chronic kidney disease after cardiac surgery. Adv. Chronic Kidney Dis. 2008;15(3):257-277. DOI 10.1053/j.ackd.2008.04.006Steiner L.A. Postoperative delirium. Part 1: Pathophysiology and risk factors. Eur. J. Anaesthesiol. 2011;28(9):628-636. DOI 10.1097/EJA.0b013e328349b7f5Steiner L.A. Postoperative delirium. Part 1: Pathophysiology and risk factors. Eur. J. Anaesthesiol. 2011;28(9):628-636. DOI 10.1097/EJA.0b013e328349b7f5Tripp B.A., Dillon S.T., Yuan M., Asara J.M., Vasunilashorn S.M., Fong T.G., Metzger E.D., Inouye S.K., Xie Z., Ngo L.H., Marcantonio E.R., Libermann T.A., Otu H.H. Targeted metabolomics analysis of postoperative delirium. Sci. Rep. 2021;11(1):1521. DOI 10.1038/s41598-020-80412-zTripp B.A., Dillon S.T., Yuan M., Asara J.M., Vasunilashorn S.M., Fong T.G., Metzger E.D., Inouye S.K., Xie Z., Ngo L.H., Marcantonio E.R., Libermann T.A., Otu H.H. Targeted metabolomics analysis of postoperative delirium. Sci. Rep. 2021;11(1):1521. DOI 10.1038/s41598-020-80412-zVutskits L., Xie Z. Lasting impact of general anaesthesia on the brain: mechanisms and relevance. Nat. Rev. Neurosci. 2016;17:705-717. DOI 10.1038/nrn.2016.128Vutskits L., Xie Z. Lasting impact of general anaesthesia on the brain: mechanisms and relevance. Nat. Rev. Neurosci. 2016;17:705-717. DOI 10.1038/nrn.2016.128Wang Y., Shen X. Postoperative delirium in the elderly: the potential neuropathogenesis. Aging Clin. Experim. Res. 2018;30(11):12871295. DOI 10.1007/s40520-018-1008-8Wang Y., Shen X. Postoperative delirium in the elderly: the potential neuropathogenesis. Aging Clin. Experim. Res. 2018;30(11):12871295. DOI 10.1007/s40520-018-1008-8Wimmer-Greinecker G., Matheis G., Brieden M., Dietrich M., Oremek G., Westphal K., Winkelmann B.R., Moritz A. Neuropsychological changes after cardiopulmonary bypass for coronary artery bypass grafting. Thorac. Cardiovasc. Surg. 1998;46(4):207-212. DOI 10.1055/s-2007-1010226Wimmer-Greinecker G., Matheis G., Brieden M., Dietrich M., Oremek G., Westphal K., Winkelmann B.R., Moritz A. Neuropsychological changes after cardiopulmonary bypass for coronary artery bypass grafting. Thorac. Cardiovasc. Surg. 1998;46(4):207-212. DOI 10.1055/s-2007-1010226Xiao M.Z., Liu C.X., Zhou L.G., Yang Y., Wang Y. Postoperative delirium, neuroinflammation, and influencing factors of postoperative delirium: a review. Medicine. 2023;102(8):e32991-e32991. DOI 10.1097/MD.0000000000032991Xiao M.Z., Liu C.X., Zhou L.G., Yang Y., Wang Y. Postoperative delirium, neuroinflammation, and influencing factors of postoperative delirium: a review. Medicine. 2023;102(8):e32991-e32991. DOI 10.1097/MD.0000000000032991Antropova E.A., Khlebodarova T.M., Demenkov P.S., Venzel A.S., Ivanisenko N.V., Gavrilenko A.D., Ivanisenko T.V., Adamovskaya A.V., Revva P.M., Lavrik I.N., Ivanisenko V.A. Computer analysis of regulation of hepatocarcinoma marker genes hypermethylated by HCV proteins. Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov Journal of Genetics and Breeding. 2022;26(8):733-742. DOI 10.18699/VJGB-22-89Antropova E.A., Khlebodarova T.M., Demenkov P.S., Venzel A.S., Ivanisenko N.V., Gavrilenko A.D., Ivanisenko T.V., Adamovskaya A.V., Revva P.M., Lavrik I.N., Ivanisenko V.A. Computer analysis of regulation of hepatocarcinoma marker genes hypermethylated by HCV proteins. Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov Journal of Genetics and Breeding. 2022;26(8):733-742. DOI 10.18699/VJGB-22-89Bartenschlager R., Lohmann V., Penin F. The molecular and structural basis of advanced antiviral therapy for hepatitis C virus infection. Nat. Rev. Microbiol. 2013;11(7):482-496. DOI 10.1038/nrmicro3046Bartenschlager R., Lohmann V., Penin F. The molecular and structural basis of advanced antiviral therapy for hepatitis C virus infection. Nat. Rev. Microbiol. 2013;11(7):482-496. DOI 10.1038/nrmicro3046Berger K.L., Kelly S.M., Jordan T.X., Tartell M.A., Randall G. Hepatitis C virus stimulates the phosphatidylinositol 4-kinase III alphadependent phosphatidylinositol 4-phosphate production that is essential for its replication. J. Virol. 2011;85(17):8870-8883. DOI 10.1128/JVI.00059-11Berger K.L., Kelly S.M., Jordan T.X., Tartell M.A., Randall G. Hepatitis C virus stimulates the phosphatidylinositol 4-kinase III alphadependent phosphatidylinositol 4-phosphate production that is essential for its replication. J. Virol. 2011;85(17):8870-8883. DOI 10.1128/JVI.00059-11Brown W.J., Chambers K., Doody A. Phospholipase A2 (PLA2) enzymes in membrane trafficking: mediators of membrane shape and function. Traffic. 2003;4(4):214-221. DOI 10.1034/j.1600-0854.2003.00078.xBrown W.J., Chambers K., Doody A. Phospholipase A2 (PLA2) enzymes in membrane trafficking: mediators of membrane shape and function. Traffic. 2003;4(4):214-221. DOI 10.1034/j.1600-0854.2003.00078.xDiehl S.A., Schmidlin H., Nagasawa M., van Haren S.D., Kwakkenbos M.J., Yasuda E., Beaumont T., Scheeren F.A., Spits H. STAT3mediated up-regulation of BLIMP1 is coordinated with BCL6 downregulation to control human plasma cell differentiation. J. Immu nol. 2008;180(7):4805-4815. DOI 10.4049/jimmunol.180.7.4805Diehl S.A., Schmidlin H., Nagasawa M., van Haren S.D., Kwakkenbos M.J., Yasuda E., Beaumont T., Scheeren F.A., Spits H. STAT3mediated up-regulation of BLIMP1 is coordinated with BCL6 downregulation to control human plasma cell differentiation. J. Immu nol. 2008;180(7):4805-4815. DOI 10.4049/jimmunol.180.7.4805Edgar R., Domrachev M., Lash A.E. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res . 2002;30(1):207-210. DOI 10.1093/nar/30.1.207Edgar R., Domrachev M., Lash A.E. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res . 2002;30(1):207-210. DOI 10.1093/nar/30.1.207Hu Y.W., Zhang P., Yang J.Y., Huang J.L., Ma X., Li S.F., Zhao J.Y., Hu Y.R., Wang Y.C., Gao J.J., Sha Y.H., Zheng L., Wang Q. Nur77 decreases atherosclerosis progression in apoE–/– mice fed a high-fat/ high-cholesterol diet. PLoS One. 2014;9(1):e87313. DOI 10.1371/journal.pone.0087313Hu Y.W., Zhang P., Yang J.Y., Huang J.L., Ma X., Li S.F., Zhao J.Y., Hu Y.R., Wang Y.C., Gao J.J., Sha Y.H., Zheng L., Wang Q. Nur77 decreases atherosclerosis progression in apoE–/– mice fed a high-fat/ high-cholesterol diet. PLoS One. 2014;9(1):e87313. DOI 10.1371/journal.pone.0087313Ivanisenko T.V., Saik O.V., Demenkov P.S., Ivanisenko N.V., Savostianov A.N., Ivanisenko V.A. ANDDigest: a new web-based module of ANDSystem for the search of knowledge in the scientific literature. BMC Bioinformatics. 2020;21(Suppl.11):228. DOI 10.1186/s12859-020-03557-8Ivanisenko T.V., Saik O.V., Demenkov P.S., Ivanisenko N.V., Savostianov A.N., Ivanisenko V.A. ANDDigest: a new web-based module of ANDSystem for the search of knowledge in the scientific literature. BMC Bioinformatics. 2020;21(Suppl.11):228. DOI 10.1186/s12859-020-03557-8Ivanisenko T.V., Demenkov P.S., Kolchanov N.A., Ivanisenko V.A. The new version of the ANDDigest tool with improved AI-based short names recognition. Int. J. Mol. Sci. 2022;23(23):14934. DOI 10.3390/ijms232314934Ivanisenko T.V., Demenkov P.S., Kolchanov N.A., Ivanisenko V.A. The new version of the ANDDigest tool with improved AI-based short names recognition. Int. J. Mol. Sci. 2022;23(23):14934. DOI 10.3390/ijms232314934Ivanisenko V.A., Saik O.V., Ivanisenko N.V., Tiys E.S., Ivanisenko T.V., Demenkov P.S., Kolchanov N.A. ANDSystem: an Associative Network Discovery System for automated literature mining in the field of biology. BMC Syst Biol. 2015;9(Suppl.2):S2. DOI 10.1186/1752-0509-9-S2-S2Ivanisenko V.A., Saik O.V., Ivanisenko N.V., Tiys E.S., Ivanisenko T.V., Demenkov P.S., Kolchanov N.A. ANDSystem: an Associative Network Discovery System for automated literature mining in the field of biology. BMC Syst Biol. 2015;9(Suppl.2):S2. DOI 10.1186/1752-0509-9-S2-S2Ivanisenko V.A., Demenkov P.S., Ivanisenko T.V., Mishchenko E.L., Saik O.V. A new version of the ANDSystem tool for automatic extraction of knowledge from scientific publications with expanded functionality for reconstruction of associative gene networks by considering tissue-specific gene expression. BMC Bioinformatics. 2019; 20(Suppl.1):34. DOI 10.1186/s12859-018-2567-6Ivanisenko V.A., Demenkov P.S., Ivanisenko T.V., Mishchenko E.L., Saik O.V. A new version of the ANDSystem tool for automatic extraction of knowledge from scientific publications with expanded functionality for reconstruction of associative gene networks by considering tissue-specific gene expression. BMC Bioinformatics. 2019; 20(Suppl.1):34. DOI 10.1186/s12859-018-2567-6Ivanisenko V.A., Gaisler E.V., Basov N.V., Rogachev A.D., Cheresiz S.V., Ivanisenko T.V., Demenkov P.S., Mishchenko E.L., Khripko O.P., Khripko Y.I., Voevoda S.M. Plasma metabolomics and gene regulatory networks analysis reveal the role of nonstructural SARSCoV-2 viral proteins in metabolic dysregulation in COVID-19 patients. Sci. Rep. 2022;12(1):19977. DOI 10.1038/s41598-022-24170-0Ivanisenko V.A., Gaisler E.V., Basov N.V., Rogachev A.D., Cheresiz S.V., Ivanisenko T.V., Demenkov P.S., Mishchenko E.L., Khripko O.P., Khripko Y.I., Voevoda S.M. Plasma metabolomics and gene regulatory networks analysis reveal the role of nonstructural SARSCoV-2 viral proteins in metabolic dysregulation in COVID-19 patients. Sci. Rep. 2022;12(1):19977. DOI 10.1038/s41598-022-24170-0Kiuchi N., Nakajima K., Ichiba M., Fukada T., Narimatsu M., Mizuno K., Hibi M., Hirano T. STAT3 is required for the gp130-mediated full activation of the c-myc gene. J. Exp. Med. 1999;189(1):63-73. DOI 10.1084/jem.189.1.63Kiuchi N., Nakajima K., Ichiba M., Fukada T., Narimatsu M., Mizuno K., Hibi M., Hirano T. STAT3 is required for the gp130-mediated full activation of the c-myc gene. J. Exp. Med. 1999;189(1):63-73. DOI 10.1084/jem.189.1.63Kolmykov S., Yevshin I., Kulyashov M., Sharipov R., Kondrakhin Y., Makeev V.J., Kulakovskiy I.V., Kel A., Kolpakov F. GTRD: an integrated view of transcription regulation. Nucleic Acids Res. 2021; 49(D1):D104-D111. DOI 10.1093/nar/gkaa1057Kolmykov S., Yevshin I., Kulyashov M., Sharipov R., Kondrakhin Y., Makeev V.J., Kulakovskiy I.V., Kel A., Kolpakov F. GTRD: an integrated view of transcription regulation. Nucleic Acids Res. 2021; 49(D1):D104-D111. DOI 10.1093/nar/gkaa1057Kong L., Fujimoto A., Nakamura M., Aoyagi H., Matsuda M., Watashi K., Suzuki R., Arita M., Yamagoe S., Dohmae N., Suzuki T., Sakamaki Y., Ichinose S., Suzuki T., Wakita T., Aizaki H. Prolactin regulatory element binding protein is involved in hepatitis C virus replication by interaction with NS4B. J. Virol. 2016;90(6):3093-3111. DOI 10.1128/JVI.01540-15Kong L., Fujimoto A., Nakamura M., Aoyagi H., Matsuda M., Watashi K., Suzuki R., Arita M., Yamagoe S., Dohmae N., Suzuki T., Sakamaki Y., Ichinose S., Suzuki T., Wakita T., Aizaki H. Prolactin regulatory element binding protein is involved in hepatitis C virus replication by interaction with NS4B. J. Virol. 2016;90(6):3093-3111. DOI 10.1128/JVI.01540-15LaPointe P., Gurkan C., Balch W.E. Mise en place – this bud’s for the Golgi. Mol. Cell. 2004;14(4):413-414. DOI 10.1016/s1097-2765(04)00267-9LaPointe P., Gurkan C., Balch W.E. Mise en place – this bud’s for the Golgi. Mol. Cell. 2004;14(4):413-414. DOI 10.1016/s1097-2765(04)00267-9Lee J.S., Tabata K., Twu W.-I., Rahman M.S., Kim H.S., Yu J.B., Jee M.H., Bartenschlager R., Jang S.K. RACK1 mediates rewiring of intracellular networks induced by hepatitis C virus infection. PLoS Pathog. 2019;15(9):e1008021. DOI 10.1371/journal.ppat.1008021Lee J.S., Tabata K., Twu W.-I., Rahman M.S., Kim H.S., Yu J.B., Jee M.H., Bartenschlager R., Jang S.K. RACK1 mediates rewiring of intracellular networks induced by hepatitis C virus infection. PLoS Pathog. 2019;15(9):e1008021. DOI 10.1371/journal.ppat.1008021Machida K., Cheng K.T., Lai C.K., Jeng K.S., Sung V.M., Lai M.M. Hepatitis C virus triggers mitochondrial permeability transition with production of reactive oxygen species, leading to DNA damage and STAT3 activation. J. Virol. 2006;80(14):7199-7207. DOI 10.1128/jvi.00321-06Machida K., Cheng K.T., Lai C.K., Jeng K.S., Sung V.M., Lai M.M. Hepatitis C virus triggers mitochondrial permeability transition with production of reactive oxygen species, leading to DNA damage and STAT3 activation. J. Virol. 2006;80(14):7199-7207. DOI 10.1128/jvi.00321-06Manna D., Aligo J., Xu C., Park W.S., Koc H., Heo W.D., Konan K.V. Endocytic Rab proteins are required for hepatitis C virus replication complex formation. Virology. 2010;398(1):21-37. DOI 10.1016/j.virol.2009.11.034Manna D., Aligo J., Xu C., Park W.S., Koc H., Heo W.D., Konan K.V. Endocytic Rab proteins are required for hepatitis C virus replication complex formation. Virology. 2010;398(1):21-37. DOI 10.1016/j.virol.2009.11.034Moradpour D., Penin F., Rice C.M. Replication of hepatitis C virus. Nat. Rev. Microbiol. 2007;5(6):453-463. DOI 10.1038/nrmicro1645Moradpour D., Penin F., Rice C.M. Replication of hepatitis C virus. Nat. Rev. Microbiol. 2007;5(6):453-463. DOI 10.1038/nrmicro1645Papic N., Maxwell C.I., Delker D.A., Liu S., Bret S.E., Heale B.S.E., Hagedorn C.H. RNA-sequencing analysis of 5′ capped RNAs identifies many new differentially expressed genes in acute hepatitis C virus infection. Viruses. 2012;4(4):581-612. DOI 10.3390/v4040581Papic N., Maxwell C.I., Delker D.A., Liu S., Bret S.E., Heale B.S.E., Hagedorn C.H. RNA-sequencing analysis of 5′ capped RNAs identifies many new differentially expressed genes in acute hepatitis C virus infection. Viruses. 2012;4(4):581-612. DOI 10.3390/v4040581Powdrill M.H., Tchesnokov E.P., Kozak R.A., Russell R.S., Martin R., Svarovskaia E.S., Mo H., Kouyos R.D., Gotte M. Contribution of a mutational bias in hepatitis C virus replication to the genetic barrier in the development of drug resistance. Proc. Natl. Acad. Sci. USA. 2011;108(51):20509-20513. DOI 10.1073/pnas.1105797108Powdrill M.H., Tchesnokov E.P., Kozak R.A., Russell R.S., Martin R., Svarovskaia E.S., Mo H., Kouyos R.D., Gotte M. Contribution of a mutational bias in hepatitis C virus replication to the genetic barrier in the development of drug resistance. Proc. Natl. Acad. Sci. USA. 2011;108(51):20509-20513. DOI 10.1073/pnas.1105797108Reiss S., Rebhan I., Backes P., Romero-Brey I., Erfle H., Matula P., Kaderali L., Poenisch M., Blankenburg H., Hiet M.S., Longerich T., Diehl S., Ramirez F., Balla T., Rohr K., Kaul A., Buhler S., Pepperkok R., Lengauer T., Albrecht M., Eils R., Schirmacher P., Lohmann V., Bartenschlager R. Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment. Cell Host Microbe. 2011; 9(1):32-45. DOI 10.1016/j.chom.2010.12.002Reiss S., Rebhan I., Backes P., Romero-Brey I., Erfle H., Matula P., Kaderali L., Poenisch M., Blankenburg H., Hiet M.S., Longerich T., Diehl S., Ramirez F., Balla T., Rohr K., Kaul A., Buhler S., Pepperkok R., Lengauer T., Albrecht M., Eils R., Schirmacher P., Lohmann V., Bartenschlager R. Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment. Cell Host Microbe. 2011; 9(1):32-45. DOI 10.1016/j.chom.2010.12.002Saik O.V., Ivanisenko T.V., Demenkov P.S., Ivanisenko V.A. Interactome of the hepatitis C virus: literature mining with ANDSystem. Virus Res. 2016;218:40-48. DOI 10.1016/j.virusres.2015.12.003Saik O.V., Ivanisenko T.V., Demenkov P.S., Ivanisenko V.A. Interactome of the hepatitis C virus: literature mining with ANDSystem. Virus Res. 2016;218:40-48. DOI 10.1016/j.virusres.2015.12.003Saik O.V., Demenkov P.S., Ivanisenko T.V., Bragina E.Y., Freidin M.B., Dosenko V.E., Zolotareva O.I., Choynzonov E.L., Hofestaedt R., Ivanisenko V.A. Search for new candidate genes involved in the comorbidity of asthma and hypertension based on automatic analysis of scientific literature. J. Integr. Bioinform. 2018a;15(4):20180054. DOI 10.1515/jib-2018-0054Saik O.V., Demenkov P.S., Ivanisenko T.V., Bragina E.Y., Freidin M.B., Dosenko V.E., Zolotareva O.I., Choynzonov E.L., Hofestaedt R., Ivanisenko V.A. Search for new candidate genes involved in the comorbidity of asthma and hypertension based on automatic analysis of scientific literature. J. Integr. Bioinform. 2018a;15(4):20180054. DOI 10.1515/jib-2018-0054Saik O.V., Demenkov P.S., Ivanisenko T.V., Bragina E.Y., Freidin M.B., Goncharova I.A., Dosenko V.E., Zolotareva O.I., Hofestaedt R., Lavrik I.N., Rogaev E.I. Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks. BMC Med. Genomics. 2018b;11(1):61-76. DOI 10.1186/s12920-018-0331-4Saik O.V., Demenkov P.S., Ivanisenko T.V., Bragina E.Y., Freidin M.B., Goncharova I.A., Dosenko V.E., Zolotareva O.I., Hofestaedt R., Lavrik I.N., Rogaev E.I. Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks. BMC Med. Genomics. 2018b;11(1):61-76. DOI 10.1186/s12920-018-0331-4Saik O.V., Nimaev V.V., Usmonov D.B., Demenkov P.S., Ivanisenko T.V., Lavrik I.N., Ivanisenko V.A. Prioritization of genes involved in endothelial cell apoptosis by their implication in lymphedema using an analysis of associative gene networks with ANDSystem. BMC Med. Genomics. 2019;12(Suppl.2):117-131. DOI 10.1186/s12920-019-0492-9Saik O.V., Nimaev V.V., Usmonov D.B., Demenkov P.S., Ivanisenko T.V., Lavrik I.N., Ivanisenko V.A. Prioritization of genes involved in endothelial cell apoptosis by their implication in lymphedema using an analysis of associative gene networks with ANDSystem. BMC Med. Genomics. 2019;12(Suppl.2):117-131. DOI 10.1186/s12920-019-0492-9Salloum S., Wang H., Ferguson C., Parton R.G., Tai A.W. Rab18 binds to hepatitis C virus NS5A and promotes interaction between sites of viral replication and lipid droplets. PLoS Pathog. 2013;9(8): e1003513. DOI 10.1371/journal.ppat.1003513Salloum S., Wang H., Ferguson C., Parton R.G., Tai A.W. Rab18 binds to hepatitis C virus NS5A and promotes interaction between sites of viral replication and lipid droplets. PLoS Pathog. 2013;9(8): e1003513. DOI 10.1371/journal.ppat.1003513Tan Y., Li Y. HCV core protein promotes hepatocyte proliferation and chemoresistance by inhibiting NR4A1. Biochem. Biophys. Res. Commun. 2015;466(3):592-598. DOI 10.1016/j.bbrc.2015.09.091Tan Y., Li Y. HCV core protein promotes hepatocyte proliferation and chemoresistance by inhibiting NR4A1. Biochem. Biophys. Res. Commun. 2015;466(3):592-598. DOI 10.1016/j.bbrc.2015.09.091Xiong J., Wang L., Fei X.C., Jiang X., Zheng Z., Zhao Y., Wang C., Li B., Chen S., Janin A., Gale R.P., Zhao W. MYC is a positive regulator of choline metabolism and impedes mitophagy-dependent necroptosis in diffuse large B-cell lymphoma. Blood Cancer J. 2017;7(7):e582. DOI 10.1038/bcj.2017.61Xiong J., Wang L., Fei X.C., Jiang X., Zheng Z., Zhao Y., Wang C., Li B., Chen S., Janin A., Gale R.P., Zhao W. MYC is a positive regulator of choline metabolism and impedes mitophagy-dependent necroptosis in diffuse large B-cell lymphoma. Blood Cancer J. 2017;7(7):e582. DOI 10.1038/bcj.2017.61Xu S., Pei R., Guo M., Han Q., Lai J., Wang Y., Wu C., Zhou Y., Lu M., Chen X. Cytosolic phospholipase A2 gamma is involved in hepatitis C virus replication and assembly. J. Virol. 2012;86(23):13025-13037. DOI 10.1128/JVI.01785-12Xu S., Pei R., Guo M., Han Q., Lai J., Wang Y., Wu C., Zhou Y., Lu M., Chen X. Cytosolic phospholipase A2 gamma is involved in hepatitis C virus replication and assembly. J. Virol. 2012;86(23):13025-13037. DOI 10.1128/JVI.01785-12Xue Y.K., Tan J., Dou D.W., Chen D., Chen L.J., Ren H.P., Chen L.B., Xiong X.G., Zheng H. Effect of Kruppel-like factor 4 on Notch pathway in hepatic stellate cells. J. Huazhong Univ. Sci. Technolog. Med. Sci. 2016;36(6):811-816. DOI 10.1007/s11596-016-1667-7Xue Y.K., Tan J., Dou D.W., Chen D., Chen L.J., Ren H.P., Chen L.B., Xiong X.G., Zheng H. Effect of Kruppel-like factor 4 on Notch pathway in hepatic stellate cells. J. Huazhong Univ. Sci. Technolog. Med. Sci. 2016;36(6):811-816. DOI 10.1007/s11596-016-1667-7Yamane D., McGivern D.R., Masaki T., Lemon S.M. Liver injury and disease pathogenesis in chronic hepatitis C. Curr. Top. Microbiol. Immunol. 2013;369:263-288. DOI 10.1007/978-3-642-27340-7_11Yamane D., McGivern D.R., Masaki T., Lemon S.M. Liver injury and disease pathogenesis in chronic hepatitis C. Curr. Top. Microbiol. Immunol. 2013;369:263-288. DOI 10.1007/978-3-642-27340-7_11Yankina M.A., Saik O.V., Ivanisenko V.A., Demenkov P.S., Khusnutdinova E.K. Evaluation of prioritization methods of extrinsic apoptotic signaling pathway genes for retrieval of the new candidates associated with major depressive disorder. Russ. J. Genet. 2018; 54(11):1366-1374. DOI 10.1134/S1022795418110170Yankina M.A., Saik O.V., Ivanisenko V.A., Demenkov P.S., Khusnutdinova E.K. Evaluation of prioritization methods of extrinsic apoptotic signaling pathway genes for retrieval of the new candidates associated with major depressive disorder. Russ. J. Genet. 2018; 54(11):1366-1374. DOI 10.1134/S1022795418110170Yevshin I., Sharipov R., Valeev T., Kel A., Kolpakov F. GTRD: a data- base of transcription factor binding sites identified by ChIP-seq experiments. Nucleic Acids Res. 2017;45(D1):D61-D67. DOI 10.1093/nar/gkw951Yevshin I., Sharipov R., Valeev T., Kel A., Kolpakov F. GTRD: a data- base of transcription factor binding sites identified by ChIP-seq experiments. Nucleic Acids Res. 2017;45(D1):D61-D67. DOI 10.1093/nar/gkw951Zong Y., Panikkar A., Xu J., Antoniou A., Raynaud P., Lemaigre F., Stanger B.Z. Notch signaling controls liver development by regulating biliary differentiation. Development. 2009;136(10):1727-1739. DOI 10.1242/dev.029140Zong Y., Panikkar A., Xu J., Antoniou A., Raynaud P., Lemaigre F., Stanger B.Z. Notch signaling controls liver development by regulating biliary differentiation. Development. 2009;136(10):1727-1739. DOI 10.1242/dev.029140

The authors declare that there are no conflicts of interest present.