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( A ) Epigenome-wide association study of dpi in PBMCs based on the entire methylation array. The volcano plots display the −log 10 ( P values) and the directionality of association between CpG sites and infection stages (A, EC, and LC) compared with B: A versus B (left panel), EC versus B (center panel), and LC versus B (right panel). Each dot represents a specific DNAme site. Shown are significantly associated CpG sites ( q < 0.05) with hypomethylation (blue), hypermethylation (red), and nonsignificant (gray). The horizontal axis represents the mean methylation change (i.e., the difference between group means), and the vertical axis represents −log 10 ( P values). ( B ) Changes in EA during each infection stage (A, EC, and LC) relative to B. Biological age analysis was performed based on subsets of clock CpGs. EA at the 3 infection time points was compared with B using mixed-effects linear regression modeling of longitudinal EA changes in PBMCs based on 10 epigenetic clocks. The results are shown separately for young (right) and old (left) RMs. Epigenetic age changes in young (blue) and old (red) RMs are shown. Saturated colors indicate statistically significant changes ( P < 0.05); pale colors indicate nonsignificant changes ( P > 0.05). A statistically significant increase in EA was observed only in young RMs. B–H, Benjamini–Hochberg correction; DMP, differentially methylated positions; dpi, days after infection; RMs, rhesus macaques; B, baseline; A, acute; EC, early chronic; LC, late chronic; EA, epigenetic age.

Journal: The Journal of Clinical Investigation

Article Title: Pathogenic SIV infection is associated with acceleration of epigenetic age in rhesus macaques

doi: 10.1172/JCI189574

Figure Lengend Snippet: ( A ) Epigenome-wide association study of dpi in PBMCs based on the entire methylation array. The volcano plots display the −log 10 ( P values) and the directionality of association between CpG sites and infection stages (A, EC, and LC) compared with B: A versus B (left panel), EC versus B (center panel), and LC versus B (right panel). Each dot represents a specific DNAme site. Shown are significantly associated CpG sites ( q < 0.05) with hypomethylation (blue), hypermethylation (red), and nonsignificant (gray). The horizontal axis represents the mean methylation change (i.e., the difference between group means), and the vertical axis represents −log 10 ( P values). ( B ) Changes in EA during each infection stage (A, EC, and LC) relative to B. Biological age analysis was performed based on subsets of clock CpGs. EA at the 3 infection time points was compared with B using mixed-effects linear regression modeling of longitudinal EA changes in PBMCs based on 10 epigenetic clocks. The results are shown separately for young (right) and old (left) RMs. Epigenetic age changes in young (blue) and old (red) RMs are shown. Saturated colors indicate statistically significant changes ( P < 0.05); pale colors indicate nonsignificant changes ( P > 0.05). A statistically significant increase in EA was observed only in young RMs. B–H, Benjamini–Hochberg correction; DMP, differentially methylated positions; dpi, days after infection; RMs, rhesus macaques; B, baseline; A, acute; EC, early chronic; LC, late chronic; EA, epigenetic age.

Article Snippet: DNAme profiles were generated using a custom Infinium methylation array (HorvathMammalMethylChip40) representing 37,492 CpG highly conserved sites in the mammals, with the NCBI’s Gene Expression Omnibus (GEO) accession number GPL28271 for microarray design ( ).

Techniques: Methylation, Infection