Combined biostatistics and bioinformatics analyses to identify epigenetically regulated host factors associated with control of HIV disease progression

Abstract

A small, but considerable proportion (1-3%) of HIV infected individuals can control their infection in the absence of antiretroviral treatment (ART), while others progress to Acquired Immune-Deficiency Syndrome (AIDS) within one or few years after infection. In this work we perform a comprehensive epigenomic study of host DNA methylation in HIV infected patients using innovative methods for omics data analysis. To do this we apply a multivariate analysis, using the R-Package “CMA” from Bioconductor. 2862 Differentially Methylated Positions (DMP) related to genes were found and the multivariate analysis identified 20 of them in 16 different genes, that could be good markers to predict the control status of the infection. From these genes, including CMPK2, CXCR5, IL7R, IL6R, PARP9 and TGFBR2, a biological and functional analysis was performed using Ingenuity Pathway Analysis Software (IPA). The application of DNA methylome to HIV infection have yielded extensive new data that identify epigenetic dysregulation of Signaling and Death Receptors as new potential deregulated pathways associated with HIV control/non-control. The data thus afford a better understanding of immune-regulatory alterations and highlight the need that future therapeutic intervention strategies may have to integrate more than single target molecules.