Genome<i>Runner</i>: automating genome exploration

Dozmorov, Mikhail G.; Cara, Lukas R.; Giles, Cory B.; Wren, Jonathan D.

doi:10.1093/bioinformatics/btr666

Cited by 26 publications

(25 citation statements)

References 14 publications

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“…The enrichment analyses were performed using GenomeRunner (46) to test whether up/downregulated CpG sites, both in the gene and non-gene regions, were enriched in any specific class of (epi)genomic annotations, as compared with randomly selected CpG sites from all 450K CpGs on the Illumina Infinium array.…”

Section: Methodsmentioning

confidence: 99%

Effects of DNA Methylation on Progression to Interstitial Fibrosis and Tubular Atrophy in Renal Allograft Biopsies: A Multi-Omics Approach

Bontha

Maluf

Archer

et al. 2017

American Journal of Transplantation

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Progressive fibrosis of the interstitium is the dominant final pathway in renal destruction in native and transplanted kidneys. Over time, the continuum of molecular events following immunological and non-immunological insults lead to interstitial fibrosis and tubular atrophy (IFTA) and culminate in kidney failure. We hypothesize that these insults trigger changes in DNA methylation (DNAm) patterns which in turn could exacerbate injury and slow down the regeneration processes, leading to fibrosis development and graft dysfunction. Herein, we analyzed biopsy samples from kidney allografts collected after 24-months post transplantation and used an integrative multi-omics approach to understand the underlying molecular mechanisms. The role of DNAm and microRNAs on the graft gene expression was evaluated. Enrichment analyses of differentially methylated CpG sites were performed using GenomeRunner. CpGs were strongly enriched in regions that were variably methylated among tissues implying high tissue specificity in their regulatory impact. Corresponding to this methylation pattern, gene expression data were related to immune response (activated state) and nephrogenesis (inhibited state). Preimplantation biopsies showed similar DNAm patterns to normal allograft biopsies at 2-years post-transplantation. Our findings demonstrate for the first time a relationship among epigenetic modifications and development of interstitial fibrosis, graft function, and inter-individual variation on long-term outcomes.

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Section: Methodsmentioning

confidence: 99%

Effects of DNA Methylation on Progression to Interstitial Fibrosis and Tubular Atrophy in Renal Allograft Biopsies: A Multi-Omics Approach

Bontha

Maluf

Archer

et al. 2017

American Journal of Transplantation

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“…35,67,68 Briefly, the enrichment analysis evaluates whether a set of aDMRs or aGENs is statistically significantly colocalizes with epigenomic datasets. The two-tailed Fisher's exact test was used to calculate enrichments, or depletions, of such colocalization.…”

Section: Epigenomic Enrichment Analysismentioning

confidence: 99%

Polycomb repressive complex 2 epigenomic signature defines age-associated hypermethylation and gene expression changes

Dozmorov

2015

Epigenetics

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Although age-associated gene expression and methylation changes have been reported throughout the literature, the unifying epigenomic principles of aging remain poorly understood. Recent explosion in availability and resolution of functional/regulatory genome annotation data (epigenomic data), such as that provided by the ENCODE and Roadmap Epigenomics projects, provides an opportunity for the identification of epigenomic mechanisms potentially altered by age-associated differentially methylated regions (aDMRs) and regulatory signatures in the promoters of ageassociated genes (aGENs). In this study we found that aDMRs and aGENs identified in multiple independent studies share a common Polycomb Repressive Complex 2 signature marked by EZH2, SUZ12, CTCF binding sites, repressive H3K27me3, and activating H3K4me1 histone modification marks, and a "poised promoter" chromatin state. This signature is depleted in RNA Polymerase II-associated transcription factor binding sites, activating H3K79me2, H3K36me3, H3K27ac marks, and an "active promoter" chromatin state. The PRC2 signature was shown to be generally stable across cell types. When considering the directionality of methylation changes, we found the PRC2 signature to be associated with aDMRs hypermethylated with age, while hypomethylated aDMRs were associated with enhancers. In contrast, aGENs were associated with the PRC2 signature independently of the directionality of gene expression changes. In this study we demonstrate that the PRC2 signature is the common epigenomic context of genomic regions associated with hypermethylation and gene expression changes in aging.

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“…Using a more liberal threshold of q-value < 0.25 resulted in 97 additional "suggestive" findings. We use GenomeRunner 50 to test for enrichment of genomic features among these 97 sites (supplementary table 2). We found a significant enrichment of sites that bind to CEBPB (q-value = 0.022).…”

Section: Cpg-snp Mwasmentioning

confidence: 99%

A Whole Methylome CpG-SNP Association Study of Psychosis in Blood and Brain Tissue

Oord

Clark

Xie

et al. 2015

SCHBUL

Self Cite

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Mutated CpG sites (CpG-SNPs) are potential hotspots for human diseases because in addition to the sequence variation they may show individual differences in DNA methylation. We performed methylome-wide association studies (MWAS) to test whether methylation differences at those sites were associated with schizophrenia. We assayed all common CpG ) was CpG-SNP rs16872141 located in the potential promoter of ENC1. Overall, our results suggested that CpG-SNP methylation may reflect effects of environmental insults and can provide biomarkers in blood that could potentially improve disease management.

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GenomeRunner: automating genome exploration

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 26 publications

References 14 publications

Effects of DNA Methylation on Progression to Interstitial Fibrosis and Tubular Atrophy in Renal Allograft Biopsies: A Multi-Omics Approach

Effects of DNA Methylation on Progression to Interstitial Fibrosis and Tubular Atrophy in Renal Allograft Biopsies: A Multi-Omics Approach

Polycomb repressive complex 2 epigenomic signature defines age-associated hypermethylation and gene expression changes

A Whole Methylome CpG-SNP Association Study of Psychosis in Blood and Brain Tissue

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