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Functions to summarize DNA methylation data using regional principal components. Regional principal components are computed using principal components analysis within genomic regions to summarize the variability in methylation levels across CpGs. The number of principal components is chosen using either the Marcenko-Pasteur or Gavish-Donoho method to identify relevant signal in the data.

Motivation: The understanding of cancer mechanism requires the identification of genes playing a role in the development of the pathology and the characterization of their role (notably oncogenes and tumor suppressors). Results: We present an R/bioconductor package called MoonlightR which returns a list of candidate driver genes for specific cancer types on the basis of TCGA expression data. The method first infers gene regulatory networks and then carries out a functional enrichment analysis (FEA) (implementing an upstream regulator analysis, URA) to score the importance of well-known biological processes with respect to the studied cancer type. Eventually, by means of random forests, MoonlightR predicts two specific roles for the candidate driver genes: i) tumor suppressor genes (TSGs) and ii) oncogenes (OCGs). As a consequence, this methodology does not only identify genes playing a dual role (e.g. TSG in one cancer type and OCG in another) but also helps in elucidating the biological processes underlying their specific roles. In particular, MoonlightR can be used to discover OCGs and TSGs in the same cancer type. This may help in answering the question whether some genes change role between early stages (I, II) and late stages (III, IV) in breast cancer. In the future, this analysis could be useful to determine the causes of different resistances to chemotherapeutic treatments.

15 flavours of betas and three performance metrics, with methods for objects produced by methylumi and minfi packages.

This package is devoted to analyzing high-throughput data (e.g. gene expression microarray, DNA methylation microarray, RNA-seq) from complex tissues. Current functionalities include 1. detect cell-type specific or cross-cell type differential signals 2. tree-based differential analysis 3. improve variable selection in reference-free deconvolution 4. partial reference-free deconvolution with prior knowledge.

The aim of TCGAbiolinks is : i) facilitate the GDC open-access data retrieval, ii) prepare the data using the appropriate pre-processing strategies, iii) provide the means to carry out different standard analyses and iv) to easily reproduce earlier research results. In more detail, the package provides multiple methods for analysis (e.g., differential expression analysis, identifying differentially methylated regions) and methods for visualization (e.g., survival plots, volcano plots, starburst plots) in order to easily develop complete analysis pipelines.

This package aims to analyse count-based methylation data on predefined genomic regions, such as those obtained by targeted sequencing, and thus to identify differentially methylated regions (DMRs) that are associated with phenotypes or traits. The method is built a rich flexible model that allows for the effects, on the methylation levels, of multiple covariates to vary smoothly along genomic regions. At the same time, this method also allows for sequencing errors and can adjust for variability in cell type mixture.

The skewr package is a tool for visualizing the output of the Illumina Human Methylation 450k BeadChip to aid in quality control. It creates a panel of nine plots. Six of the plots represent the density of either the methylated intensity or the unmethylated intensity given by one of three subsets of the 485,577 total probes. These subsets include Type I-red, Type I-green, and Type II.The remaining three distributions give the density of the Beta-values for these same three subsets. Each of the nine plots optionally displays the distributions of the "rs" SNP probes and the probes associated with imprinted genes as series of 'tick' marks located above the x-axis.

SingleMoleculeFootprinting provides functions to analyze Single Molecule Footprinting (SMF) data. Following the workflow exemplified in its vignette, the user will be able to perform basic data analysis of SMF data with minimal coding effort. Starting from an aligned bam file, we show how to perform quality controls over sequencing libraries, extract methylation information at the single molecule level accounting for the two possible kind of SMF experiments (single enzyme or double enzyme), classify single molecules based on their patterns of molecular occupancy, plot SMF information at a given genomic location.

Interactive tool for visualizing Illumina methylation array data. Both the 450k and EPIC array are supported.

Tools For analyzing Illumina Infinium DNA methylation arrays. SeSAMe provides utilities to support analyses of multiple generations of Infinium DNA methylation BeadChips, including preprocessing, quality control, visualization and inference. SeSAMe features accurate detection calling, intelligent inference of ethnicity, sex and advanced quality control routines.

Functions to analyze methylation data can be found here. Some functions are relevant for single cell methylation data but most other functions can be used for any methylation data. Highlight of this workflow is the comprehensive quality control report.

RnBeads facilitates comprehensive analysis of various types of DNA methylation data at the genome scale.

Machine learning-based tools to predict DNA methylation of locus-specific repetitive elements (RE) by learning surrounding genetic and epigenetic information. These tools provide genomewide and single-base resolution of DNA methylation prediction on RE that are difficult to measure using array-based or sequencing-based platforms, which enables epigenome-wide association study (EWAS) and differentially methylated region (DMR) analysis on RE.

Resources for cross-study analyses of public DNAm array data from NCBI GEO repo, produced using Illumina's Infinium HumanMethylation450K (HM450K) and MethylationEPIC (EPIC) platforms. Provided functions enable download, summary, and filtering of large compilation files. Vignettes detail background about file formats, example analyses, and more. Note the disclaimer on package load and consult the main manuscripts for further info.

Bioconductor-native infrastructure for handling large nanoporetech modkit bedMethyl pileup files from ONT data using HDF5Array and DelayedArray.

A complete toolset for methylome-wide association studies (MWAS). It is specifically designed for data from enrichment based methylation assays, but can be applied to other data as well. The analysis pipeline includes seven steps: (1) scanning aligned reads from BAM files, (2) calculation of quality control measures, (3) creation of methylation score (coverage) matrix, (4) principal component analysis for capturing batch effects and detection of outliers, (5) association analysis with respect to phenotypes of interest while correcting for top PCs and known covariates, (6) annotation of significant findings, and (7) multi-marker analysis (methylation risk score) using elastic net. Additionally, RaMWAS include tools for joint analysis of methlyation and genotype data. This work is published in Bioinformatics, Shabalin et al. (2018) <doi:10.1093/bioinformatics/bty069>.

ramr is an R package for detection of epimutations (i.e., infrequent aberrant DNA methylation events) in large data sets obtained by methylation profiling using array or high-throughput methylation sequencing. In addition, package provides functions to visualize found aberrantly methylated regions (AMRs), to generate sets of all possible regions to be used as reference sets for enrichment analysis, and to generate biologically relevant test data sets for performance evaluation of AMR/DMR search algorithms.

The understanding of cancer mechanism requires the identification of genes playing a role in the development of the pathology and the characterization of their role (notably oncogenes and tumor suppressors). We present an updated version of the R/bioconductor package called MoonlightR, namely Moonlight2R, which returns a list of candidate driver genes for specific cancer types on the basis of omics data integration. The Moonlight framework contains a primary layer where gene expression data and information about biological processes are integrated to predict genes called oncogenic mediators, divided into putative tumor suppressors and putative oncogenes. This is done through functional enrichment analyses, gene regulatory networks and upstream regulator analyses to score the importance of well-known biological processes with respect to the studied cancer type. By evaluating the effect of the oncogenic mediators on biological processes or through random forests, the primary layer predicts two putative roles for the oncogenic mediators: i) tumor suppressor genes (TSGs) and ii) oncogenes (OCGs). As gene expression data alone is not enough to explain the deregulation of the genes, a second layer of evidence is needed. We have automated the integration of a secondary mutational layer through new functionalities in Moonlight2R. These functionalities analyze mutations in the cancer cohort and classifies these into driver and passenger mutations using the driver mutation prediction tool, CScape-somatic. Those oncogenic mediators with at least one driver mutation are retained as the driver genes. As a consequence, this methodology does not only identify genes playing a dual role (e.g. TSG in one cancer type and OCG in another) but also helps in elucidating the biological processes underlying their specific roles. In particular, Moonlight2R can be used to discover OCGs and TSGs in the same cancer type. This may for instance help in answering the question whether some genes change role between early stages (I, II) and late stages (III, IV). In the future, this analysis could be useful to determine the causes of different resistances to chemotherapeutic treatments. An additional mechanistic layer evaluates if there are mutations affecting the protein stability of the transcription factors (TFs) of the TSGs and OCGs, as that may have an effect on the expression of the genes.

This package provides classes for holding and manipulating Illumina methylation data. Based on eSet, it can contain MIAME information, sample information, feature information, and multiple matrices of data. An "intelligent" import function, methylumiR can read the Illumina text files and create a MethyLumiSet. methylumIDAT can directly read raw IDAT files from HumanMethylation27 and HumanMethylation450 microarrays. Normalization, background correction, and quality control features for GoldenGate, Infinium, and Infinium HD arrays are also included.

MethylSig is a package for testing for differentially methylated cytosines (DMCs) or regions (DMRs) in whole-genome bisulfite sequencing (WGBS) or reduced representation bisulfite sequencing (RRBS) experiments. MethylSig uses a beta binomial model to test for significant differences between groups of samples. Several options exist for either site-specific or sliding window tests, and variance estimation.

methylscaper is an R package for processing and visualizing data jointly profiling methylation and chromatin accessibility (MAPit, NOMe-seq, scNMT-seq, nanoNOMe, etc.). The package supports both single-cell and single-molecule data, and a common interface for jointly visualizing both data types through the generation of ordered representational methylation-state matrices. The Shiny app allows for an interactive seriation process of refinement and re-weighting that optimally orders the cells or DNA molecules to discover methylation patterns and nucleosome positioning.

MethylMix is an algorithm implemented to identify hyper and hypomethylated genes for a disease. MethylMix is based on a beta mixture model to identify methylation states and compares them with the normal DNA methylation state. MethylMix uses a novel statistic, the Differential Methylation value or DM-value defined as the difference of a methylation state with the normal methylation state. Finally, matched gene expression data is used to identify, besides differential, functional methylation states by focusing on methylation changes that effect gene expression. References: Gevaert 0. MethylMix: an R package for identifying DNA methylation-driven genes. Bioinformatics (Oxford, England). 2015;31(11):1839-41. doi:10.1093/bioinformatics/btv020. Gevaert O, Tibshirani R, Plevritis SK. Pancancer analysis of DNA methylation-driven genes using MethylMix. Genome Biology. 2015;16(1):17. doi:10.1186/s13059-014-0579-8.

methylKit is an R package for DNA methylation analysis and annotation from high-throughput bisulfite sequencing. The package is designed to deal with sequencing data from RRBS and its variants, but also target-capture methods and whole genome bisulfite sequencing. It also has functions to analyze base-pair resolution 5hmC data from experimental protocols such as oxBS-Seq and TAB-Seq. Methylation calling can be performed directly from Bismark aligned BAM files.

This package allows to estimate missing values in DNA methylation data. methyLImp method is based on linear regression since methylation levels show a high degree of inter-sample correlation. Implementation is parallelised over chromosomes since probes on different chromosomes are usually independent. Mini-batch approach to reduce the runtime in case of large number of samples is available.

The main functions for methylGSA are methylglm and methylRRA. methylGSA implements logistic regression adjusting number of probes as a covariate. methylRRA adjusts multiple p-values of each gene by Robust Rank Aggregation. For more detailed help information, please see the vignette.

This package allows to estimate chronological and gestational DNA methylation (DNAm) age as well as biological age using different methylation clocks. Chronological DNAm age (in years) : Horvath's clock, Hannum's clock, BNN, Horvath's skin+blood clock, PedBE clock and Wu's clock. Gestational DNAm age : Knight's clock, Bohlin's clock, Mayne's clock and Lee's clocks. Biological DNAm clocks : Levine's clock and Telomere Length's clock.

A visual and interactive web application using RStudio's shiny package. Bad quality samples are detected using sample-dependent and sample-independent controls present on the array and user adjustable thresholds. In depth exploration of bad quality samples can be performed using several interactive diagnostic plots of the quality control probes present on the array. Furthermore, the impact of any batch effect provided by the user can be explored.

Bedgraph files generated by Bisulfite pipelines often come in various flavors. Critical downstream step requires summarization of these files into methylation/coverage matrices. This step of data aggregation is done by Methrix, including many other useful downstream functions.

DNA methylation is generally considered to be associated with transcriptional silencing. However, comprehensive, genome-wide investigation of this relationship requires the evaluation of potentially millions of correlation values between the methylation of individual genomic loci and expression of associated transcripts in a relatively large numbers of samples. Methodical makes this process quick and easy while keeping a low memory footprint. It also provides a novel method for identifying regions where a number of methylation sites are consistently strongly associated with transcriptional expression. In addition, Methodical enables housing DNA methylation data from diverse sources (e.g. WGBS, RRBS and methylation arrays) with a common framework, lifting over DNA methylation data between different genome builds and creating base-resolution plots of the association between DNA methylation and transcriptional activity at transcriptional start sites.

MEDIPS was developed for analyzing data derived from methylated DNA immunoprecipitation (MeDIP) experiments followed by sequencing (MeDIP-seq). However, MEDIPS provides functionalities for the analysis of any kind of quantitative sequencing data (e.g. ChIP-seq, MBD-seq, CMS-seq and others) including calculation of differential coverage between groups of samples and saturation and correlation analysis.

Package to integrate methylation and expression data. It can also perform methylation or expression analysis alone. Several plotting functionalities are included as well as a new region analysis based on redundancy analysis. Effect of SNPs on a region can also be estimated.

This package provides a function for reconstructing DNA methylation values from raw measurements. It iteratively implements the group fused lars to smooth related-by-location methylation values and the constrained least squares to remove probe affinity effect across multiple sequences.

The Lheuristic package identifies scatterpots that follow and L-shaped, negative distribution. It can be used to identify genes regulated by methylation by integration of an expression and a methylation array. The package uses two different methods to detect expression and methyaltion L- shapped scatterplots. The parameters can be changed to detect other scatterplot patterns.

In epigenome-wide association studies, the measured signals for each sample are a mixture of methylation profiles from different cell types. The current approaches to the association detection only claim whether a cytosine-phosphate-guanine (CpG) site is associated with the phenotype or not, but they cannot determine the cell type in which the risk-CpG site is affected by the phenotype. We propose a solid statistical method, HIgh REsolution (HIRE), which not only substantially improves the power of association detection at the aggregated level as compared to the existing methods but also enables the detection of risk-CpG sites for individual cell types. The "HIREewas" R package is to implement HIRE model in R.

Provides a function to normalize Illumina Infinium Human Methylation 450 BeadChip (Illumina 450K), correcting for tissue and/or cell type.

The package includes some statistical outlier detection methods for epimutations detection in DNA methylation data. The methods included in the package are MANOVA, Multivariate linear models, isolation forest, robust mahalanobis distance, quantile and beta. The methods compare a case sample with a suspected disease against a reference panel (composed of healthy individuals) to identify epimutations in the given case sample. It also contains functions to annotate and visualize the identified epimutations.

EpiDISH is a R package to infer the proportions of a priori known cell-types present in a sample representing a mixture of such cell-types. Right now, the package can be used on DNAm data of blood-tissue of any age, from birth to old-age, generic epithelial tissue and breast tissue. Besides, the package provides a function that allows the identification of differentially methylated cell-types and their directionality of change in Epigenome-Wide Association Studies.

Epialleles are specific DNA methylation patterns that are mitotically and/or meiotically inherited. This package calls and reports cytosine methylation as well as frequencies of hypermethylated epialleles at the level of genomic regions or individual cytosines in next-generation sequencing data using binary alignment map (BAM) files as an input. Among other things, this package can also extract and visualise methylation patterns and assess allele specificity of methylation.

Tools for quanlity control, analysis and visulization of Illumina DNA methylation array data.

ELMER is designed to use DNA methylation and gene expression from a large number of samples to infere regulatory element landscape and transcription factor network in primary tissue.

This package provides a collection of functions designed for analyzing deconvolution of the bulk sample(s) using an atlas of reference omic signature profiles and a user-selected model. Users are given the option to create or extend a reference atlas and,also simulate the desired size of the bulk signature profile of the reference cell types.The package includes the cell-type-specific methylation atlas and, Illumina Epic B5 probe ids that can be used in deconvolution. Additionally,we included BSmeth2Probe, to make mapping WGBS data to their probe IDs easier.

'DAMEfinder' offers functionality for taking methtuple or bismark outputs to calculate ASM scores and compute DAMEs. It also offers nice visualization of methyl-circle plots.

coMethDMR identifies genomic regions associated with continuous phenotypes by optimally leverages covariations among CpGs within predefined genomic regions. Instead of testing all CpGs within a genomic region, coMethDMR carries out an additional step that selects co-methylated sub-regions first without using any outcome information. Next, coMethDMR tests association between methylation within the sub-region and continuous phenotype using a random coefficient mixed effects model, which models both variations between CpG sites within the region and differential methylation simultaneously.

Tools for finding bumps in genomic data

A collection of tools for analyzing and visualizing whole-genome methylation data from sequencing. This includes whole-genome bisulfite sequencing and Oxford nanopore data.

Methods for working with Illumina arrays using gdsfmt.

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.

Perform the Adaptive Robust Regression method (ARRm) for the normalization of methylation data from the Illumina Infinium HumanMethylation 450k assay.