Dataset Information

DMRcaller: a versatile R/Bioconductor package for detection and visualization of differentially methylated regions in CpG and non-CpG contexts.

ABSTRACT: DNA methylation has been associated with transcriptional repression and detection of differential methylation is important in understanding the underlying causes of differential gene expression. Bisulfite-converted genomic DNA sequencing is the current gold standard in the field for building genome-wide maps at a base pair resolution of DNA methylation. Here we systematically investigate the underlying features of detecting differential DNA methylation in CpG and non-CpG contexts, considering both the case of mammalian systems and plants. In particular, we introduce DMRcaller, a highly efficient R/Bioconductor package, which implements several methods to detect differentially methylated regions (DMRs) between two samples. Most importantly, we show that different algorithms are required to compute DMRs and the most appropriate algorithm in each case depends on the sequence context and levels of methylation. Furthermore, we show that DMRcaller outperforms other available packages and we propose a new method to select the parameters for this tool and for other available tools. DMRcaller is a comprehensive tool for differential methylation analysis which displays high sensitivity and specificity for the detection of DMRs and performs entire genome wide analysis within a few hours.

SUBMITTER: Catoni M

PROVIDER: S-EPMC6212837 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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DMRcaller: a versatile R/Bioconductor package for detection and visualization of differentially methylated regions in CpG and non-CpG contexts.

Catoni Marco M Tsang Jonathan Mf JM Greco Alessandro P AP Zabet Nicolae Radu NR

Nucleic acids research 20181101 19

DNA methylation has been associated with transcriptional repression and detection of differential methylation is important in understanding the underlying causes of differential gene expression. Bisulfite-converted genomic DNA sequencing is the current gold standard in the field for building genome-wide maps at a base pair resolution of DNA methylation. Here we systematically investigate the underlying features of detecting differential DNA methylation in CpG and non-CpG contexts, considering bo ...[more]

PMID: 29986099

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Project description:BACKGROUND:Psychiatric symptomatology during late childhood and early adolescence tends to persist later in life. In the present longitudinal study, we aimed to identify changes in genome-wide DNA methylation patterns that were associated with the emergence of psychopathology in youths from the Brazilian High-Risk Cohort (HRC) for psychiatric disorders. Moreover, for the differentially methylated genes, we verified whether differences in DNA methylation corresponded to differences in mRNA transcript levels by analyzing the gene expression levels in the blood and by correlating the variation of DNA methylation values with the variation of mRNA levels of the same individuals. Finally, we examined whether the variations in DNA methylation and mRNA levels were correlated with psychopathology measurements over time. METHODS:We selected 24 youths from the HRC who presented with an increase in dimensional psychopathology at a 3-year follow-up as measured by the Child Behavior Checklist (CBCL). The DNA methylation and gene expression data were compared in peripheral blood samples (n?=?48) obtained from the 24 youths before and after developing psychopathology. We implemented a methodological framework to reduce the effect of chronological age on DNA methylation using an independent population of 140 youths and the effect of puberty using data from the literature. RESULTS:We identified 663 differentially methylated positions (DMPs) and 90 differentially methylated regions (DMRs) associated with the emergence of psychopathology. We observed that 15 DMPs were mapped to genes that were differentially expressed in the blood; among these, we found a correlation between the DNA methylation and mRNA levels of RB1CC1 and a correlation between the CBCL and mRNA levels of KMT2E. Of the DMRs, three genes were differentially expressed: ASCL2, which is involved in neurogenesis; HLA-E, which is mapped to the MHC loci; and RPS6KB1, the gene expression of which was correlated with an increase in the CBCL between the time points. CONCLUSIONS:We observed that changes in DNA methylation and, consequently, in gene expression in the peripheral blood occurred concurrently with the emergence of dimensional psychopathology in youths. Therefore, epigenomic modulations might be involved in the regulation of an individual's development of psychopathology.

Dataset Information

DMRcaller: a versatile R/Bioconductor package for detection and visualization of differentially methylated regions in CpG and non-CpG contexts.

Publications

DMRcaller: a versatile R/Bioconductor package for detection and visualization of differentially methylated regions in CpG and non-CpG contexts.

Similar Datasets

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