DISMISS

BACKGROUND: DNA methylation is an important regulator of gene expression and
chromatin structure. Methylated DNA immunoprecipitation sequencing (MeDIP-Seq) is
commonly used to identify regions of DNA methylation in eukaryotic genomes.
Within MeDIP-Seq libraries, methylated cytosines can be found in both
double-stranded (symmetric) and single-stranded (asymmetric) genomic contexts.
While symmetric CG methylation has been relatively well-studied, asymmetric
methylation in any dinucleotide context has received less attention. Importantly,
no currently available software for processing MeDIP-Seq reads is able to resolve
these strand-specific DNA methylation signals. Here we introduce DISMISS, a new
software package that detects strand-associated DNA methylation from existing
MeDIP-Seq analyses. RESULTS: Using MeDIP-Seq datasets derived from Apis mellifera
(honeybee), an invertebrate species that contains more asymmetric- than
symmetric- DNA methylation, we demonstrate that DISMISS can identify
strand-specific DNA methylation signals with similar accuracy as bisulfite
sequencing (BS-Seq; single nucleotide resolution methodology). Specifically,
DISMISS is able to confidently predict where DNA methylation predominates (plus
or minus DNA strands - asymmetric DNA methylation; plus and minus DNA stands -
symmetric DNA methylation) in MeDIP-Seq datasets derived from A. mellifera
samples. When compared to DNA methylation data derived from BS-Seq analysis of A.
mellifera worker larva, DISMISS-mediated identification of strand-specific
methylated cytosines is 80 % accurate. Furthermore, DISMISS can correctly (p
<0.0001) detect the origin (sense vs antisense DNA strands) of DNA methylation at
splice site junctions in A. mellifera MeDIP-Seq datasets with a precision close
to BS-Seq analysis. Finally, DISMISS-mediated identification of DNA methylation
signals associated with upstream, exonic, intronic and downstream genomic loci
from A. mellifera MeDIP-Seq datasets outperforms MACS2 (Model-based Analysis of
ChIP-Seq2; a commonly used MeDIP-Seq analysis software) and closely approaches
the results achieved by BS-Seq. CONCLUSIONS: While asymmetric DNA methylation is
increasingly being found in growing numbers of eukaryotic species and is the
predominant pattern observed in some invertebrate genomes, it has been difficult
to detect in MeDIP-Seq datasets using existing software. DISMISS now enables more
sensitive examinations of MeDIP-Seq datasets and will be especially useful for
the study of genomes containing either low levels of DNA methylation or for
genomes containing relatively high amounts of asymmetric methylation.

DISMISS: detection of stranded methylation in MeDIP-Seq data.

DISMISS is a software tool to detect strand-associated DNA methylation in Methylated DNA immunoprecipitation sequencing (MeDIP-Seq) data.

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