AI-Assisted Identification of Primary and Secondary Metabolomic Markers for Post-Operative Delirium

Author:

Lomivorotov Vladimir1,Ivanisenko Vladimir2,Makarova Aelita-Luiza3,Rogachev Artem4ORCID,Basov Nikita4ORCID,Gaisler Evgeniy4,Kuzmicheva Irina5,Demenkov Pavel2,Venzel Artur2ORCID,Ivanisenko Timofey2,Antropova Evgenia3,Naidanova Margarita6,Kolchanov Nikolay5,Kochetov Alexey5,Plesko Victoria7,Moroz Gleb7,Pokrovsky Andrey6

Affiliation:

1. Penn State Hershey Medical Center, Penn State College of Medicine

2. Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk State University, Kurchatov Genomic Center of ICG SB RAS, Novosibirsk, Russia

3. Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia

4. Novosibirsk State University, N. N. Vorozhtsov Institute of Organic Chemistry, Novosibirsk, Russia

5. Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk State University, Novosibirsk, Russia

6. Novosibirsk State University, Novosibirsk, Russia

7. E. Meshalkin National Medical Research Center, Novosibirsk, Russia; Department of Anesthesiology and Intensive Care

Abstract

Abstract 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), 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, 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 bioinformatic analysis of metabolomic data which could aid in uncovering potential primary and secondary markers in diverse research domains.

Publisher

Research Square Platform LLC

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