Despite considerable investigative efforts, the molecular mechanisms of postoperative delirium (POD) remain unresolved. The present investigation employs innovative methodologies for identifying potential primary and secondary metabolic markers of POD by analyzing serum metabolomic profiles utilizing the genetic algorithm and artificial neural networks. The primary metabolomic markers constitute a combination of metabolites that optimally distinguish between POD and non-POD groups of patients. Our analysis revealed L-lactic acid, inositol, and methylcysteine as the most salient primary markers upon which the prediction accuracy of POD manifestation achieved AUC = 99%. The secondary metabolomic markers represent metabolites that exhibit perturbed correlational patterns within the POD group. We identified 54 metabolites as the secondary markers of POD, incorporating neurotransmitters such as gamma-aminobutyric acid (GABA) and serotonin. These findings imply a systemic disruption in metabolic processes in patients with POD. The deployment of gene network reconstruction techniques facilitated the postulation of hypotheses describing the role of established genomic POD markers in the molecular-genetic mechanisms of metabolic pathways dysregulation, and involving the identified primary and secondary metabolomic markers. This study not only expands the understanding of POD pathogenesis but also introduces a novel technology for the bioinformatic analysis of metabolomic data that could aid in uncovering potential primary and secondary markers in diverse research domains.

The plant cell wall represents the outer compartment of the plant cell, which provides a physical barrier and triggers signaling cascades under the influence of biotic and abiotic stressors. Drought is a factor that negatively affects both plant growth and development. Cell wall proteins (CWP) play an important role in the plant response to water deficit. The adaptation mechanisms of the cell wall to water loss are of interest for identifying important genetic factors determining plant drought resistance and provide valuable information on biomarkers for further selection aimed at increasing the yield of crop plants. Using ANDSystem, a gene network describing the regulation of CWPs under water restriction conditions was reconstructed. The analysis of the gene network and the transcriptome data analysis allowed prioritizing transcription factors (TF) based on their enrichment of differentially expressed genes regulated by them. As a result, scores were calculated, acting as indicators of the association of TFs with water deficit. On the basis of the score values, eight most significant TFs were selected. The highest priority was given to the TF GBF3. CWPs were prioritized according to the criterion of summing up the scores of transcription factors regulating these genes. Among the most prioritized CWPs were the AT5G03350 gene encoding a lectin-like protein, AT4G20860 encoding BBE-like 22 required for the oxidation of cellulose degradation products, and AT4G37800 encoding xyloglucan endotransglucosy lase/hydrolase 7. Overall, the implemented algorithm could be used for prediction of regulatory interactions between transcription factors and target genes encoding cell wall proteins in plants.

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.

Parkinson’s disease (PD) and vascular parkinsonism (VP) are characterized by similar neurological syndromes but differ in pathogenesis, morphology, and therapeutic approaches. The molecular genetic mechanisms of these pathologies are multifactorial and involve multiple biological processes. To comprehensively analyze the pathophysiology of PD and VP, the methods of systems biology and gene network reconstruction are essential. In the current study, we performed metabolomic screening of amino acids and acylcarnitines in blood plasma of three groups of subjects: PD patients, VP patients and the control group. Comparative statistical analysis of the metabolic profiles identified significantly altered metabolites in the PD and the VP group. To identify potential mechanisms of amino acid and acylcarnitine metabolism disorders in PD and VP, regulatory gene networks were reconstructed using ANDSystem, a cognitive system. Regulatory pathways to the enzymes converting significant metabolites were found from PD­specific genetic markers, VP­specific genetic markers, and the group of genetic markers common to the two diseases. Comparative analysis of molecular genetic pathways in gene networks allowed us to identify both specific and non­specific molecular mechanisms associated with changes in the metabolomic profile in PD and VP. Regulatory pathways with potentially impaired function in these pathologies were discovered. The regulatory pathways to the enzymes ALDH2, BCAT1, AL1B1, and UD11 were found to be specific for PD, while the pathways regulating OCTC, FURIN, and S22A6 were specific for VP. The pathways regulating BCAT2, ODPB and P4HA1 were associated with genetic markers common to both diseases. The results obtained deepen the understanding of pathological processes in PD and VP and can be used for application of diagnostic systems based on the evaluation of the amino acids and acylcarnitines profile in blood plasma of patients with PD and VP.

Primary open-angle glaucoma (POAG) is the most common form of glaucoma. This condition leads to optic nerve degeneration and eventually to blindness. Tobacco smoking, alcohol consumption, fast-food diets, obesity, heavy weight lifting, high-intensity physical exercises, and many other bad habits are lifestyle-related risk factors for POAG. By contrast, moderate-intensity aerobic exercise and the Mediterranean diet can alleviate POAG. In this work, we for the first time estimated the phylostratigraphic age indices (PAIs) of all 153 POAG-related human genes in the NCBI Gene Database. This allowed us to separate them into two groups: POAG-related genes that appeared before and after the phylum Chordata, that is, ophthalmologically speaking, before and after the camera-type eye evolved. Next, in the POAG-related genes’ promoters, we in silico predicted all 3835 candidate SNP markers that significantly change the TATA-binding protein (TBP) affinity for these promoters and, through this molecular mechanism, the expression levels of these genes. Finally, we verified our results against five independent web services—PANTHER, DAVID, STRING, MetaScape, and GeneMANIA—as well as the ClinVar database. It was concluded that POAG is likely to be a symptom of the human self-domestication syndrome, a downside of being civilized.

Anxiety is a normotypic human condition, and like any other emotion has an adaptive value. But excessively high or low anxiety has negative consequences for adaptation, which primarily determines the importance of studying these two extreme conditions. At the same time, it is known that the perception of aversive stimuli associated with anxiety leads to changes in the activity of the brain’s cingulate cortex. The advantage of animals as models in studying the genetic bases of anxiety in humans is in the ability to subtly control the external conditions of formation of a certain state, the availability of brain tissues, and the ability to create and study transgenic models, including through the use of differentially expressed genes of small laboratory animals from the family Muridae with low and high anxiety. Within the framework of the translational approach, a three-domain potential gene network, which is associated with generalized anxiety in humans, was reconstructed using mouse models with different levels of anxiety by automatically analyzing the texts of scientific articles. One domain is associated with reduced anxiety in humans, the second with increased anxiety, and the third is a dispatcher who activates one of the two domains depending on the status of the organism (genetic, epigenetic, physiological). Stages of work: (I) A list of genes expressed in the cingulate cortex of the wild type CD-1 mouse line from the NCBI GEO database (experiment GSE29014). Using the tools of this database, differences in gene expression levels were revealed in groups of mice with low and high (relatively normal) anxiety. (II) Search for orthologs of DEG in humans and mice associated with anxiety in the OMA Orthology database. (III) Computer reconstruction using the ANDSystem cognitive system based on (a) human orthologous genes from stage (III), (b) human genes from the MalaCards database associated with human anxiety. The proven methods of the translational approach for the reconstruction of gene networks for behavior regulation can be used to identify molecular genetic markers of human personality traits, propensity to psychopathology.