DMCHMM

DifferentialMethylation

A pipeline for identifying differentially methylated CpG sites using Hidden Markov Model in bisulfite sequencing data. DNA methylation studies have enabled researchers to understand methylation patterns and their regulatory roles in biological processes and disease. However, only a limited number of statistical approaches have been developed to provide formal quantitative analysis. Specifically, a few available methods do identify differentially methylated CpG (DMC) sites or regions (DMR), but they suffer from limitations that arise mostly due to challenges inherent in bisulfite sequencing data. These challenges include: (1) that read-depths vary considerably among genomic positions and are often low; (2) both methylation and autocorrelation patterns change as regions change; and (3) CpG sites are distributed unevenly. Furthermore, there are several methodological limitations: almost none of these tools is capable of comparing multiple groups and/or working with missing values, and only a few allow continuous or multiple covariates. The last of these is of great interest among researchers, as the goal is often to find which regions of the genome are associated with several exposures and traits. To tackle these issues, we have developed an efficient DMC identification method based on Hidden Markov Models (HMMs) called “DMCHMM” which is a three-step approach (model selection, prediction, testing) aiming to address the aforementioned drawbacks.

Source attribution

  • BioconductorDMCHMM

Related resources

A novel approach utilizing a homogeneous hidden Markov model. And effectively model untransformed beta values. To identify DMCs while considering the spatial. Correlation of the adjacent CpG sites.

Generate HTML or PDF reports to explore a set of regions such as the results from annotation-agnostic expression analysis of RNA-seq data at base-pair resolution performed by derfinder. You can also create reports for DESeq2 or edgeR results.

91 month ago
R
Artistic-2.0

This is a probabilistic modelling pipeline for computing per- nucleotide posterior probabilities of modification from the data collected in structure probing experiments. The model supports multiple experimental replicates and empirically corrects coverage- and sequence-dependent biases. The model utilises the measure of a "drop-off rate" for each nucleotide, which is compared between replicates through a log-ratio (LDR). The LDRs between control replicates define a null distribution of variability in drop-off rate observed by chance and LDRs between treatment and control replicates gets compared to this distribution. Resulting empirical p-values (probability of being "drawn" from the null distribution) are used as observations in a Hidden Markov Model with a Beta-Uniform Mixture model used as an emission model. The resulting posterior probabilities indicate the probability of a nucleotide of having being modified in a structure probing experiment.

This package builds on the Epimods framework which facilitates finding weighted subnetworks ("modules") on Illumina Infinium 27k arrays using the SpinGlass algorithm, as implemented in the iGraph package. We have created a class of gene centric annotations associated with p-values and effect sizes and scores from any researchers prior statistical results to find functional modules.

This package implements functions for calling methylation for all cytosines in the genome.

DMCFB is a pipeline for identifying differentially methylated cytosines using a Bayesian functional regression model in bisulfite sequencing data. By using a functional regression data model, it tries to capture position-specific, group-specific and other covariates-specific methylation patterns as well as spatial correlation patterns and unknown underlying models of methylation data. It is robust and flexible with respect to the true underlying models and inclusion of any covariates, and the missing values are imputed using spatial correlation between positions and samples. A Bayesian approach is adopted for estimation and inference in the proposed method.