Synergic Integration of the miRNome, Machine Learning and Bioinformatics for the Identification of Potential Disease-Modifying Agents in Obstructive Sleep Apnea

作者：Thalía Belmonte, Ivan David Benitez, María C. García‐Hidalgo, Marta Molinero, Lucía Pinilla, Olga Mínguez, Rafaela Vaca, Maria Aguilà, Anna Moncusí‐Moix, Gerard Torres, Olga Mediano, Juan F. Masa, María José Masdeu, Blanca Montero-San-Martín, Mercè Ibarz, Pablo Martínez‐Camblor, Alberto Gómez‐Carballa, Antonio Salas, Federico Martinón‐Torres, Ferrán Barbé, Manuel Sánchez‐de‐la‐Torre, David de Gonzalo‐Calvo · 发表于：Archivos de Bronconeumología · 年份：2024 · DOI：10.1016/j.arbres.2024.11.011 · 被引用次数：10 · 研究领域：Obstructive Sleep Apnea Research、MicroRNA in disease regulation、Cardiovascular Disease and Adiposity

INTRODUCTION: Understanding the diverse pathogenetic pathways in obstructive sleep apnea (OSA) is crucial for improving outcomes. microRNA (miRNA) profiling is a promising strategy for elucidating these mechanisms. OBJECTIVE: To characterize the pathogenetic pathways linked to OSA through the integration of miRNA profiles, machine learning (ML) and bioinformatics. METHODS: This multicenter study involved 525 patients with suspected OSA who underwent polysomnography. Plasma miRNAs were quantified via RNA sequencing in the discovery phase, with validation in two subsequent phases using RT-qPCR. Supervised ML feature selection methods and comprehensive bioinformatic analyses were employed. The associations among miRNA targets, OSA and OSA treatment were further explored using publicly available external datasets. RESULTS: Following the discovery and technical validation phases in a subset of patients with and without confirmed OSA (n=53), eleven miRNAs were identified as candidates for the subsequent feature selection process. These miRNAs were then quantified in the remaining population (n=472). Feature selection methods revealed that the miRNAs let-7d-5p, miR-15a-5p and miR-107 were the most informative of OSA. The predominant mechanisms linked to these miRNAs were closely related to cellular events such as cell death, cell differentiation, extracellular remodeling, autophagy and metabolism. One target of let-7d-5p and miR-15a-5p, the TFDP2 gene, exhibited significant differen...