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Background DNA methylation-regulated genes have been demonstrated as the crucial participants in the occurrence of coronary heart disease (CHD). The machine learning based on DNA methylation-regulated genes has tremendous potential for mining non-invasive predictive biomarkers and exploring underlying new mechanisms of CHD. Results First, the 2085 age-gender-matched individuals in Framingham Heart Study (FHS) were randomly divided into training set and validation set. We then integrated methylome and transcriptome data of peripheral blood leukocytes (PBLs) from the training set to probe into the methylation and expression patterns of CHD-related genes. A total of five hub DNA methylation-regulated genes were identified in CHD through dimensionality reduction, including ATG7, BACH2, CDKN1B, DHCR24 and MPO. Subsequently, methylation and expression features of the hub DNA methylation-regulated genes were used to construct machine learning models for CHD prediction by LightGBM, XGBoost and Random Forest. The optimal model established by LightGBM exhibited favorable predictive capacity, whose AUC, sensitivity, and specificity were 0.834, 0.672, 0.864 in the validation set, respectively. Furthermore, the methylation and expression statuses of the hub genes were verified in monocytes using methylation microarray and transcriptome sequencing. The methylation statuses of ATG7, DHCR24 and MPO and the expression statuses of ATG7, BACH2 and DHCR24 in monocytes of our study population were consistent with those in PBLs from FHS. Conclusions We identified five DNA methylation-regulated genes based on a predictive model for CHD using machine learning, which may clue the new epigenetic mechanism for CHD.

A number of processes and pathways have been reported in the development of Group I pulmonary hypertension (Group I PAH); however, novel biomarkers need to be identified for a better diagnosis and management. We employed a robust rank aggregation (RRA) algorithm to shortlist the key differentially expressed genes (DEGs) between Group I PAH patients and controls. An optimal diagnostic model was obtained by comparing seven machine learning algorithms and was verified in an independent dataset. The functional roles of key DEGs and biomarkers were analyzed using various in silico methods. Finally, the biomarkers and a set of key candidates were experimentally validated using patient samples and a cell line model. A total of 48 key DEGs with preferable diagnostic value were identified. A gradient boosting decision tree algorithm was utilized to build a diagnostic model with three biomarkers, PBRM1, CA1, and TXLNG. An immune-cell infiltration analysis revealed significant differences in the relative abundances of seven immune cells between controls and PAH patients and a correlation with the biomarkers. Experimental validation confirmed the upregulation of the three biomarkers in Group I PAH patients. In conclusion, machine learning and a bioinformatics analysis along with experimental techniques identified PBRM1, CA1, and TXLNG as potential biomarkers for Group I PAH.