Integrated Multi-Omics Analysis of Cerebrospinal Fluid in Postoperative Delirium.
Bridget A TrippSimon T DillonMin YuanJohn M AsaraSarinnapha M VasunilashornTamara G FongSharon K InouyeLong H NgoMarcantonio ErZhongcong XieLibermann TaHasan H OtuPublished in: Biomolecules (2024)
Preoperative risk biomarkers for delirium may aid in identifying high-risk patients and developing intervention therapies, which would minimize the health and economic burden of postoperative delirium. Previous studies have typically used single omics approaches to identify such biomarkers. Preoperative cerebrospinal fluid (CSF) from the Healthier Postoperative Recovery study of adults ≥ 63 years old undergoing elective major orthopedic surgery was used in a matched pair delirium case-no delirium control design. We performed metabolomics and lipidomics, which were combined with our previously reported proteomics results on the same samples. Differential expression, clustering, classification, and systems biology analyses were applied to individual and combined omics datasets. Probabilistic graph models were used to identify an integrated multi-omics interaction network, which included clusters of heterogeneous omics interactions among lipids, metabolites, and proteins. The combined multi-omics signature of 25 molecules attained an AUC of 0.96 [95% CI: 0.85-1.00], showing improvement over individual omics-based classification. We conclude that multi-omics integration of preoperative CSF identifies potential risk markers for delirium and generates new insights into the complex pathways associated with delirium. With future validation, this hypotheses-generating study may serve to build robust biomarkers for delirium and improve our understanding of its pathophysiology.
Keyphrases
- single cell
- cardiac surgery
- patients undergoing
- hip fracture
- cerebrospinal fluid
- rna seq
- machine learning
- healthcare
- acute kidney injury
- mass spectrometry
- deep learning
- randomized controlled trial
- public health
- end stage renal disease
- newly diagnosed
- minimally invasive
- gene expression
- ejection fraction
- chronic kidney disease
- coronary artery disease
- risk assessment
- prognostic factors
- convolutional neural network
- atrial fibrillation
- health information
- dna methylation