Use of Two Complementary Bioinformatic Approaches to Identify Differentially Methylated Regions in Neonatal Sepsis

Neonatal sepsis is a heterogeneous condition affecting preterm infants whose underlying mechanisms remain unknown. The analysis of changes in the DNA methylation pattern can contribute to improving the understanding of molecular pathways underlying disease pathophysiology. Methylation EPIC 850K BeadChip technology is an excellent tool for genome-wide methylation analyses and the detection of differentially methylated regions (DMRs). The aim is to identify DNA methylation traits in complex diseases, such as neonatal sepsis, using data from Methylation EPIC 850K BeadChip arrays. Two different bioinformatic methods, DMRcate (a supervised approach) and mCSEA (an unsupervised approach), were used to identify DMRs using EPIC data from leukocytes of neonatal septic patients. Here, we describe with detail the implementation of both methods as well as their applicability, briefly discussing the results obtained for neonatal sepsis. Differences in methylation levels were observed in neonatal sepsis patients. Moreover, differences were identified between the two subsets of the disease: Early-Onset neonatal Sepsis (EOS) and Late-Onset Neonatal Sepsis (LOS). This approach by using DMRcate and mCSA helped us to gain insight into the intricate mechanisms that may drive EOS and LOS development and progression in newborns.