Identification of metabolic biomarkers in idiopathic pulmonary arterial hypertension using targeted metabolomics and bioinformatics analysis

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 th...

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Vydané v:	Scientific reports Ročník 14; číslo 1; s. 25283 - 15
Hlavní autori:	Yang, Chuang, Liu, Yi-Hang, Zheng, Hai-Kuo
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 25.10.2024 Nature Publishing Group Nature Portfolio
Predmet:	631/114 692/308 692/4019 692/53 692/699 Adult Algorithms Biochemical pathways Bioinformatics Biomarkers Biomarkers - blood Biosynthesis Case-Control Studies Computational Biology - methods Diagnosis 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 Hypertension Idiopathic pulmonary arterial hypertension Learning algorithms Liquid chromatography Machine Learning Male Mass spectrometry Mass spectroscopy Metabolism Metabolites Metabolome Metabolomics Metabolomics - methods Middle Aged multidisciplinary Phenotypes Pulmonary hypertension Science Science (multidisciplinary) Spermine Tryptophan Biomarkers Idiopathic pulmonary arterial hypertension Metabolomics Biochemical pathways Machine learning
ISSN:	2045-2322, 2045-2322
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-024-76514-7