Comparison of genomic DNA methylation pattern among septic and non-septic newborns — An epigenome wide association study

AbstractDNA methylation is the current strategy in the field of biomarker discovery due to its prognostic efficiency. Its role in prognosis and early diagnosis has been recognized in various types of cancer. Sepsis still remains one of the major causes of neonatal mortality. Delay in diagnosis of sepsis leads to treatment difficulties and poor outcome. In this study, we have done an epigenome wide search to identify potential markers for prognosis of neonatal sepsis which may improve the treatment strategies. We analyzed the CpG methylation status in the epigenome of three septic and non-septic babies using Illumina Infinium HumanMethylation450K methylation microarray. The microarray data was analyzed with Illumina GenomeStudio v2011.1. After screening for biological and clinical significance, we found 81 differentially methylated CpGs located in 64 genes. Bioinformatic analysis using DAVID and GeneMania revealed a panel of differentially methylated protocadherin beta (PCDHB) genes that play vital role in leukocyte cell adhesion and Wnt signaling pathway. Apart, genes like CCS, DNAJA3, and DEGS2 were potentially hyper/hypo methylated which can be utilized in the development of novel biomarkers. This study will be helpful in exploring the role of DNA methylation in the pathophysiology of neonatal sepsis. The complete microarray data can be accessed from the public domain, Gene Expression Omnibus of NCBI (http://www.ncbi.nlm.nih.gov/geo/). The accession number is GSE58651