README.md

In andigoni/MeinteR: A framework to prioritize DNA methylation aberrations based on conformational and cis-regulatory element enrichment

Introduction

MeinteR (MEthylation INTERpretation) is an R package that identifies critical differentially methylated sites, based on the following hypothesis: Critical methylation-mediated changes are more likely in genomic regions enriched in cis-acting regulatory elements than in genomic “deserts”. MeinteR calculates the abundance of co-localized elements, such as transcription factor binding sites, tentative splice sites, and other DNA features, such as G-quadruplexes and palindromes that potentially lead to distinct DNA conformational features and rank them with respect to their putative methylation impact.

Main features

• Identification of conformational and cis-regulatory DNA elements:
• G-quadruplex structures
• Palindromes
• Splice sites and known alternative splicing events
• Putative transcription factors and human/mouse/rat conserved transcription factors
• Shape features (minor groove width, roll, propeller twist and helix twist)
• Evaluation of genomic substrate enrichment
• Building genomic signatures of each CpG site
• Prioritizing DNA methylation targets
• Batch analysis of user-defined sequence lengths centered at the CpG targets
• Connection with public data repositories e.g. GEO, TCGA/GDC data retrieval
• Auxiliary functions for plotting, converting data

Package files

Binary Package

Source Package

Package Vignette (PDF) (HTML)

Package Manual (PDF)

Installation

1) Install from GitHub

To install MeinteR and all its dependencies first you need to install devtools in R version >=3.5.3 ("Great Truth"). Upon successful installation run the following command:

devtools::install_github("andigoni/meinter")

2) Install local distribution (source)

First, download the source distribution of the package and run the following command in R console (set path appropriately):

install.packages("<PATH_TO_MEINTER>/MeinteR_0.99.0.tar.gz", repos = NULL, type = "source")

Example use cases

The results of the three use cases presented in the manuscript can be reproduced by running the corresponding source code:

Use Case 1: Genome-wide association of G-quadruplexes with DNA methylation using TCGA/GEO breast cancer datasets

Use Case 2: Evaluation of genomic signatures on cancer methylation profiles

Use Case 3: Associating genomic DMS signatures with gene expression

Demo run

Here is a simple run demonstrating the main functionalities on a sample dataset pre-loaded with the MeinteR package.

library(MeinteR)
rm(list = ls())
#Reorder columns of sample dataset
re.sample <- reorderBed(sample, 1, 2, 3, 5, 4)
#Select sites with delta-beta > 0.50
bed.data <- re.sample[re.sample$score >= 0.50,] 
#Find overlaps with alternative splicing events
altSS <- findAltSplicing(bed.data)
#Find overlaps with splice sites
ss <- findSpliceSites(bed.data, persim = 0.8, offset = 10)
#Find palindromic sequences
pals <- findPals(bed.data)
#Find G-quadruplexes
quads <- findQuads(bed.data, offset = 50)
#Find overlaps with "MA0107.1", "MA0098", "MA115.1", "MA0131.2 transcription factors
tfbs <-
  findTFBS(
    bed.data,
    target = "all",
    tf.ID = c("MA0107.1", "MA0098", "MA115.1", "MA0131.2")
  )
#Find overlaps with conserved transcription factors. ~71MB gzipped file 
#will be downloaded if local path is not set.
ctfbs <- findConservedTFBS(bed.data)
#Find overlaps with DNA shape features
shapes <- findShapes(bed.data)
#Feature weights
weights = list()
weights[["spls"]] = 1
weights[["ctfbs"]] = 1
weights[["tfbs"]] = 1
weights[["pals"]] = 1
weights[["quads"]] = 1
weights[["shapes"]] = 1
#Mapping MeinteR arguments with function outputs
funList = list()
funList[["spls"]] = ss
funList[["altss"]] = altSS
funList[["tfbs"]] = tfbs
funList[["ctfbs"]] = ctfbs
funList[["pals"]] = pals
funList[["quads"]] = quads
funList[["shapes"]] = shapes
#Calculate genomic index
index <- meinter(re.sample, funList, weights)

Contribution, bugs and fixes

Any contribution by either reporting an issue or suggest further improvements will be appreciated. Refer to the Issues and Wiki pages of the package for more recent posts.

Citation

Malousi, Andigoni, et al. "MeinteR: A framework to prioritize DNA methylation aberrations based on conformational and cis-regulatory element enrichment." Scientific reports 9.1 (2019): 1-12.

License

The package is licensed under GPL version 3.

andigoni/MeinteR documentation built on Oct. 1, 2021, 9:33 p.m.