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forkedTF: Representing Transcription Factor Dimer Binding Sites Using Forked-Position Weight Matrices and Forked-Sequence Logos

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forkedTF

forkedTF is an R-library that generates Forked-PMW (FPMW) and Forked-Sequence Logos (F-Logos) for a better depiction of the sequence affinity (DNA sequence and DNA methylation level) of a TF of interest together with those of a segregated list of partners. Indeed, in contrast to current methods that aggregate binding sites of dimer TFs into a single PWM/logo, FPWM and F-Logo represent dimer partner PWM and sequence logos as forked from the main TF motif. Consequently, forkedTF improves PWM models of TF dimers, thereby enhancing our understanding of TF cooperativity, and opens a novel avenue for accurate TFBS prediction.

Current version: 1.0.0

Installation

Type the following in R console:

install.packages("devtools")
library("devtools")
devtools::install_github("https://github.com/benoukraflab/forkedTF")

Dependencies

Documentation

A detailed description of all forkedTF's features is available here.

Quick usage

MiniCofactor Report

This function helps in the exploration of binding partners in a cell line. Input the mainTF, cell line of interest and the cobinding_threshold to generate a PDF report of the binding partners.

library("forkedTF")
miniCofactorReport(TF = "JUND",cell = "HepG2")

In addition to finding the factor with the highest peak overlap, using the parameter filterBy="q.significance" we can compute a -log10(Adjusted P-value) from an enrichment test as implemented in https://github.com/remap-cisreg/ReMapEnrich

library("forkedTF")
miniCofactorReport(TF = "JUND",cell = "HepG2", filterBy="q.significance"

FPWM creation and plot

Use the createFPWM function to extract the motif, from empirical datasets, that a TF uses when binding with a partner TF. plotFPWM helps in visualizing the FPWM.

fpwm <- createFPWM(mainTF ="CEBPB",
                        partners = c("ATF4","ATF7","ATF3","JUND","FOS","CEBPD"),
                        cell = "K562", 
                        forkPosition = 5,
                        flipMatrix = FALSE)

plotFPWM(fpwm,pdfName="fpwm_plot.pdf")

Writing FPWM

Save the FPWM to a local file can be used in matrix scanning or matrix clustering in transfact format or FPWMtransfact format. Transfact format will have a matrix for each interacting partner in the FPWM, while FPWMtransfact will output a single matrix.

write.FPWM(FPWM = fpwm, format = "transfac", fileName = "FPWM.transfact" )
write.FPWM(FPWM = fpwm, format = "FPWMtransfac", fileName = "FPWM.FPWMtransfac" )

Cite

A manuscript describing forkedTF has been submitted. If you are currently using forkedTF, please cite us as follows:

Tirado-Magallanes R, Santana-Garcia W, Ghayour-Khiavi A, Lin QXX, Usefi H, Jha S, Thomas-Chollier M, Thieffry D, Benoukraf T. Representing Transcription Factor Dimer Binding Sites Using Forked-Position Weight Matrices and Forked-Sequence Logos. version: 0.1.0, 2020, [website: https://github.com/benoukraflab/forkedTF]

License

This project is licensed under GNU General Public License - see LICENSE.txt for details.

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forkedTF: Representing Transcription Factor Dimer Binding Sites Using Forked-Position Weight Matrices and Forked-Sequence Logos

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