Gene networks for use in metabolomic data analysis of blood plasma from patients with postoperative delirium
Postoperative delirium (POD) is considered one of the most severe complications, resulting in impaired cognitive function, extended hospitalization, and higher treatment costs. The challenge of early POD diagnosis becomes particularly significant in cardiac surgery cases, as the incidence of this co...
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Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2023-12-01
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| Series: | Вавиловский журнал генетики и селекции |
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| Online Access: | https://vavilov.elpub.ru/jour/article/view/3976 |
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| author | V. A. Ivanisenko N. V. Basov A. A. Makarova A. S. Venzel A. D. Rogachev P. S. Demenkov T. V. Ivanisenko M. A. Kleshchev E. V. Gaisler G. B. Moroz V. V. Plesko Y. S. Sotnikova Y. V. Patrushev V. V. Lomivorotov N. A. Kolchanov A. G. Pokrovsky |
| author_facet | V. A. Ivanisenko N. V. Basov A. A. Makarova A. S. Venzel A. D. Rogachev P. S. Demenkov T. V. Ivanisenko M. A. Kleshchev E. V. Gaisler G. B. Moroz V. V. Plesko Y. S. Sotnikova Y. V. Patrushev V. V. Lomivorotov N. A. Kolchanov A. G. Pokrovsky |
| author_sort | V. A. Ivanisenko |
| collection | DOAJ |
| description | Postoperative delirium (POD) is considered one of the most severe complications, resulting in impaired cognitive function, extended hospitalization, and higher treatment costs. The challenge of early POD diagnosis becomes particularly significant in cardiac surgery cases, as the incidence of this complication exceeds 50 % in certain patient categories. While it is known that neuroinflammation, neurotransmitter imbalances, disruptions in neuroendocrine regulation, and interneuronal connections contribute significantly to the development of POD, the molecular, genetic mechanisms of POD in cardiac surgery patients, along with potential metabolomic diagnostic markers, remain in adequately understood. In this study, blood plasma was collected from a group of patients over 65 years old after cardiac surgery involving artificial circulation. The collected samples were analyzed for sphingomyelin content and quantity using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS/MS) me thods. The analysis revealed four significantly different sphingomyelin contents in patients with POD compared to those who did not develop POD (control group). Employing gene network reconstruction, we perceived a set of 82 regulatory enzymes affiliated with the genetic coordination of the sphingolipid metabolism pathway. Within this set, 47 are assumed to be regulators of gene expression, governing the transcription of enzymes pivotal to the metabolic cascade. Complementing this, an additional assembly of 35 regulators are considered to be regulators of activity, degradation, and translocation dynamics of enzymes integral to the aforementioned pathway. Analysis of the overrepresentation of diseases with which these regulatory proteins are associated showed that the regulators can be categorized into two groups, associated with cardiovascular pathologies (CVP) and neuropsychiatric diseases (NPD), respectively. The regulators associated with CVP are expectedly related to the effects on myocardial tissue during surgery. It is hypothesized that dysfunction of NPD-associated regulators may specifically account for the development of POD after cardiac surgery. Thus, the identified regulatory genes may provide a basis for planning further experiments, in order to study disorders at the level of expression of these genes, as well as impaired function of proteins encoded by them in patients with POD. The identified significant sphingolipids can be considered as potential markers of POD. |
| format | Article |
| id | doaj-art-b5bed912331e41ad892e51b85b853c3c |
| institution | Kabale University |
| issn | 2500-3259 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj-art-b5bed912331e41ad892e51b85b853c3c2025-02-01T09:58:12ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592023-12-0127776877510.18699/VJGB-23-891404Gene networks for use in metabolomic data analysis of blood plasma from patients with postoperative deliriumV. A. Ivanisenko0N. V. Basov1A. A. Makarova2A. S. Venzel3A. D. Rogachev4P. S. Demenkov5T. V. Ivanisenko6M. A. Kleshchev7E. V. Gaisler8G. B. Moroz9V. V. Plesko10Y. S. Sotnikova11Y. V. Patrushev12V. V. Lomivorotov13N. A. Kolchanov14A. G. Pokrovsky15Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University; Kurchatov Genomic Center of ICG SB RASNovosibirsk State University; N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Kurchatov Genomic Center of ICG SB RASNovosibirsk State University; N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University; Kurchatov Genomic Center of ICG SB RASInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University; Kurchatov Genomic Center of ICG SB RASInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesNovosibirsk State University; N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of the Siberian Branch of the Russian Academy of SciencesE. Meshalkin National Medical Research Center of the Ministry of Health of Russian FederationE. Meshalkin National Medical Research Center of the Ministry of Health of Russian FederationNovosibirsk State University; N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of the Siberian Branch of the Russian Academy of Sciences; Boreskov Institute of Catalysis of the Siberian Branch of the Russian Academy of SciencesNovosibirsk State University; Boreskov Institute of Catalysis of the Siberian Branch of the Russian Academy of SciencesE. Meshalkin National Medical Research Center of the Ministry of Health of Russian Federation; Penn State Health Milton S. Hershey Medical CenterInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityNovosibirsk State UniversityPostoperative delirium (POD) is considered one of the most severe complications, resulting in impaired cognitive function, extended hospitalization, and higher treatment costs. The challenge of early POD diagnosis becomes particularly significant in cardiac surgery cases, as the incidence of this complication exceeds 50 % in certain patient categories. While it is known that neuroinflammation, neurotransmitter imbalances, disruptions in neuroendocrine regulation, and interneuronal connections contribute significantly to the development of POD, the molecular, genetic mechanisms of POD in cardiac surgery patients, along with potential metabolomic diagnostic markers, remain in adequately understood. In this study, blood plasma was collected from a group of patients over 65 years old after cardiac surgery involving artificial circulation. The collected samples were analyzed for sphingomyelin content and quantity using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS/MS) me thods. The analysis revealed four significantly different sphingomyelin contents in patients with POD compared to those who did not develop POD (control group). Employing gene network reconstruction, we perceived a set of 82 regulatory enzymes affiliated with the genetic coordination of the sphingolipid metabolism pathway. Within this set, 47 are assumed to be regulators of gene expression, governing the transcription of enzymes pivotal to the metabolic cascade. Complementing this, an additional assembly of 35 regulators are considered to be regulators of activity, degradation, and translocation dynamics of enzymes integral to the aforementioned pathway. Analysis of the overrepresentation of diseases with which these regulatory proteins are associated showed that the regulators can be categorized into two groups, associated with cardiovascular pathologies (CVP) and neuropsychiatric diseases (NPD), respectively. The regulators associated with CVP are expectedly related to the effects on myocardial tissue during surgery. It is hypothesized that dysfunction of NPD-associated regulators may specifically account for the development of POD after cardiac surgery. Thus, the identified regulatory genes may provide a basis for planning further experiments, in order to study disorders at the level of expression of these genes, as well as impaired function of proteins encoded by them in patients with POD. The identified significant sphingolipids can be considered as potential markers of POD.https://vavilov.elpub.ru/jour/article/view/3976lc-ms/msmetabolomicslipidomicspostoperative deliriumcardiac surgerybiomarkerssphingolipidsgene networksandsystem |
| spellingShingle | V. A. Ivanisenko N. V. Basov A. A. Makarova A. S. Venzel A. D. Rogachev P. S. Demenkov T. V. Ivanisenko M. A. Kleshchev E. V. Gaisler G. B. Moroz V. V. Plesko Y. S. Sotnikova Y. V. Patrushev V. V. Lomivorotov N. A. Kolchanov A. G. Pokrovsky Gene networks for use in metabolomic data analysis of blood plasma from patients with postoperative delirium Вавиловский журнал генетики и селекции lc-ms/ms metabolomics lipidomics postoperative delirium cardiac surgery biomarkers sphingolipids gene networks andsystem |
| title | Gene networks for use in metabolomic data analysis of blood plasma from patients with postoperative delirium |
| title_full | Gene networks for use in metabolomic data analysis of blood plasma from patients with postoperative delirium |
| title_fullStr | Gene networks for use in metabolomic data analysis of blood plasma from patients with postoperative delirium |
| title_full_unstemmed | Gene networks for use in metabolomic data analysis of blood plasma from patients with postoperative delirium |
| title_short | Gene networks for use in metabolomic data analysis of blood plasma from patients with postoperative delirium |
| title_sort | gene networks for use in metabolomic data analysis of blood plasma from patients with postoperative delirium |
| topic | lc-ms/ms metabolomics lipidomics postoperative delirium cardiac surgery biomarkers sphingolipids gene networks andsystem |
| url | https://vavilov.elpub.ru/jour/article/view/3976 |
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