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Identification of metabolic biomarkers in idiopathic pulmonary arterial hypertension using targeted metabolomics and bioinformatics analysis
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Identification of metabolic biomarkers in idiopathic pulmonary arterial hypertension using targeted metabolomics and bioinformatics analysis
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Journal Article
Identification of metabolic biomarkers in idiopathic pulmonary arterial hypertension using targeted metabolomics and bioinformatics analysis
2024
Overview
Pulmonary arterial hypertension (PAH) is a life-threatening disease with a poor prognosis, and metabolic abnormalities play a critical role in its development. This study used metabolomics, machine learning algorithms and bioinformatics to screen for potential metabolic biomarkers associated with the diagnosis of PAH. In this study, plasma samples were collected from 17 patients diagnosed with idiopathic pulmonary arterial hypertension (IPAH) and 20 healthy controls. Plasma metabolomic profiling was performed by high-performance liquid chromatography-mass spectrometry. Gene profiles of PAH patients were obtained from the GEO database. Key differentially expressed metabolites (DEMs) and metabolism-related genes were subsequently identified using machine learning algorithms. Twenty differential plasma metabolites associated with IPAH were identified (VIP score > 1 and
p
< 0 0.05), and enrichment analysis revealed the arginine biosynthesis pathway as the most altered pathway. Using machine learning models, including least absolute shrinkage and selection operator (LASSO), random forest (RF) and support vector machine (SVM), we extracted key metabolites that correlated with clinical phenotypes. Our results suggested that five metabolites, kynurenine, homoserine, tryptophan, AMP, and spermine, are potential biomarkers for IPAH. Bioinformatics analysis also identified 3 metabolism-related genes, MAPK6, SLC7A11 and CDC42BPA, that are strongly correlated with pulmonary hypertension, demonstrating strong predictive power and clinical relevance. Our findings revealed some key genes associated with metabolism in PH, and provided crucial information about complex metabolic reprogramming signals and may lead to the identification of useful metabolic biomarkers for the diagnosis of PAH.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 692/308
/ 692/4019
/ 692/53
/ 692/699
/ Adult
/ Computational Biology - methods
/ Familial Primary Pulmonary Hypertension - blood
/ Familial Primary Pulmonary Hypertension - genetics
/ Familial Primary Pulmonary Hypertension - metabolism
/ Female
/ High-performance liquid chromatography
/ Humanities and Social Sciences
/ Humans
/ Idiopathic pulmonary arterial hypertension
/ Male
/ Science
/ Spermine
