Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk 630090, Russia.
The Artificial Intelligence Research Center of Novosibirsk State University, Novosibirsk 630090, Russia.
Int J Mol Sci. 2024 Nov 4;25(21):11847. doi: 10.3390/ijms252111847.
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.
尽管进行了大量的研究,但术后谵妄(POD)的分子机制仍未得到解决。本研究采用创新方法,通过利用遗传算法和人工神经网络分析血清代谢组学图谱,来鉴定 POD 的潜在原发性和继发性代谢标志物。原发性代谢标志物是一组能够最佳地区分 POD 患者和非 POD 患者的代谢物组合。我们的分析表明,L-乳酸、肌醇和甲基半胱氨酸是 POD 表现预测准确性达到 AUC=99%的最显著原发性标志物。继发性代谢标志物代表 POD 组内表现出紊乱相关模式的代谢物。我们确定了 54 种代谢物作为 POD 的继发性标志物,其中包括神经递质如γ-氨基丁酸(GABA)和血清素。这些发现表明 POD 患者的代谢过程出现了系统性紊乱。基因网络重建技术的应用有助于提出假设,描述已建立的基因组 POD 标志物在代谢途径失调的分子遗传机制中的作用,并涉及鉴定的原发性和继发性代谢标志物。这项研究不仅扩展了对 POD 发病机制的理解,还引入了一种新的代谢组学数据分析的生物信息学分析技术,这可能有助于揭示不同研究领域的潜在原发性和继发性标志物。