Dhas D Benet Bosco, Ashmi A Hiasindh, Bhat B Vishnu, Kalaivani S, Parija Subash Chandra
Department of Pediatrics, JIPMER, Pondicherry 605006, India.
Department of Microbiology, JIPMER, Pondicherry 605006, India.
Genom Data. 2014 Nov 15;3:36-40. doi: 10.1016/j.gdata.2014.11.004. eCollection 2015 Mar.
DNA 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.
由于DNA甲基化具有预后评估效能，它是生物标志物发现领域当前采用的策略。其在各种类型癌症的预后及早期诊断中的作用已得到认可。脓毒症仍然是新生儿死亡的主要原因之一。脓毒症诊断延迟会导致治疗困难及预后不良。在本研究中，我们进行了全表观基因组搜索，以识别新生儿脓毒症预后的潜在标志物，这可能会改善治疗策略。我们使用Illumina Infinium HumanMethylation450K甲基化微阵列分析了三名脓毒症和非脓毒症婴儿表观基因组中的CpG甲基化状态。微阵列数据使用Illumina GenomeStudio v2011.1进行分析。在筛选生物学和临床意义后，我们发现81个差异甲基化的CpG位于64个基因中。使用DAVID和GeneMania进行的生物信息学分析揭示了一组差异甲基化的原钙黏蛋白β（PCDHB）基因，它们在白细胞细胞黏附和Wnt信号通路中起重要作用。此外，像CCS、DNAJA3和DEGS2这样的基因可能存在高甲基化/低甲基化，可用于开发新型生物标志物。本研究将有助于探索DNA甲基化在新生儿脓毒症病理生理学中的作用。完整的微阵列数据可从公共领域NCBI的基因表达综合数据库（http://www.ncbi.nlm.nih.gov/geo/）获取。登录号为GSE58651。
