Machine Learning in Identifying Marker Genes for Congenital Heart Diseases of Different Cardiac Cell Types

Congenital heart disease (CHD) represents a spectrum of inborn heart defects influenced by genetic and environmental factors. This study advances the field by analyzing gene expression profiles in 21, 034 cardiac fibroblasts, 73, 296 cardiomyocytes, and 35, 673 endothelial cells, utilizing single-cell level analysis and machine learning techniques. Six CHD conditions: dilated cardiomyopathy (DCM), donor hearts (used as healthy controls), hypertrophic cardiomyopathy (HCM), heart failure with hypoplastic left heart syndrome (HFHLHS), Neonatal Hypoplastic Left Heart Syndrome (NeoHLHS), and Tetralogy of Fallot (TOF), were investigated for each cardiac cell type. Each cell sample was represented by 29, 266 gene features. These features were first analyzed by six feature-ranking algorithms, resulting in several feature lists. Then, these lists were fed into incremental feature selection, containing two classification algorithms, to extract essential gene features and classification rules and build efficient classifiers. The identified essential genes can be potential CHD markers in different cardiac cell types. For instance, the LASSO identified key genes specific to various heart cell types in CHD subtypes.