Machine learning applied to serum and cerebrospinal fluid metabolomes revealed altered arginine metabolism in neonatal sepsis with meningoencephalitis

机器学习应用于血清和脑脊液代谢组学分析,揭示了新生儿败血症合并脑膜脑炎患者精氨酸代谢的改变

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Abstract

BACKGROUND: Neonatal sepsis with meningoencephalitis is a common complication of sepsis, which is a leading cause of neonatal death and neurological dysfunction. Early identification of neonatal sepsis with meningoencephalitis is particularly important for reducing brain damage. We recruited 70 patients with neonatal sepsis, 42 of which were diagnosed as meningoencephalitis, and collected cerebrospinal fluid (CSF) and serum samples. The purpose of this study was to find neonatal sepsis with meningoencephalitis-related markers using unbiased metabolomics technology and artificial intelligence analysis based on machine learning methods. RESULTS: We found that the characteristics of neonatal sepsis with meningoencephalitis were manifested mainly as significant decreases in the concentrations of homo-l-arginine, creatinine, and other arginine metabolites in serum and CSF, suggesting possible changes in nitric oxide synthesis. The antioxidants taurine and proline in the serum of the neonatal sepsis with meningoencephalitis increased significantly, suggesting abnormal oxidative stress. Potentially harmful bile salts and aromatic compounds were significantly increased in the serum of the group with meningoencephalitis. We compared different machine learning methods and found that the lasso algorithm performed best. Combining the lasso and XGBoost algorithms was successful in predicting the concentration of homo-l-arginine in CSF per the concentrations of metabolite markers in the serum. CONCLUSIONS: On the basis of machine learning combined with analysis of the serum and CSF metabolomes, we found metabolite markers related to neonatal sepsis with meningoencephalitis. The characteristics of neonatal sepsis with meningoencephalitis were manifested mainly by changes in arginine metabolism and related changes in creatinine metabolism.

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