In summary, through multiomics analysis of DNA methylation, transcriptome, and single-cell atlas data, this study identified novel NEC-related genes potentially regulated by DNA methylation, namely, ADAP1, GUCA2A, IL22RA1 and MISP, and their aberrant promoter CpG methylation status in NEC was further verified. The gene discussed is MISP; the disease is necrotizing enterocolitis.