Global Methylation Patterns in Idiopathic Pulmonary Fibrosis

Idiopathic Pulmonary Fibrosis (IPF) is a chronic progressive lung disease that affects more than 5 million people worldwide with a steady increase in both incidence and mortality. There is currently no effective therapy and the median survival without transplant is 2-5 years. The etiological factor is unknown, but several observational and pathogenesis studies suggest that environmental agents may cause IPF. DNA methylation is a type of chemical modification of DNA such environmental and occupational factors, that can induced a changes in the regulation of biological processes and link to diseases such as a cancer. We hypothesize that the global changes in methylation patterns of IPF lungs caused by environmental factors. In this study we will identify the global methylation signatures of the IPF lung and to compare to methylation signature of lung cancer. The DNA methylation profiles of IPF lung tissue differs from control lung but it shares great similarity with that of lung cancer. Immunoprecipitated methylated DNA from 12 IPF lungs, 10 lung adenocarcinomas and 10 normal histology lungs obtained from the same group of adenocarcinoma patients was hybridized to Agilent human CpG Islands Microarrays. Only probes with a hybridization Tm value between 79 C and 93C were included in the analysis because these show higher quality signal. All probes were divided according to their Tm into 14 groups/bins differing by 1C. Probe signals in each bin were standardized to have an average of 0 and a standard deviation of 1. To work in a CpG island oriented manner, we scored each island for its likelihood to be methylated. For that purpose, each probe was mapped to the genome and the signals of the probes that were mapped to a single CpG island were averaged to obtain the island’s methylation score. Data analysis was performed using BRB-Array Tools and DAVID Bioinformatics Resources software packages.