TOBIAS - Transcription factor Occupancy prediction By Investigation of ATAC-seq Signal

Introduction

ATAC-seq (Assay for Transposase-Accessible Chromatin using high-throughput sequencing) is a sequencing assay for investigating genome-wide chromatin accessibility. The assay applies a Tn5 Transposase to insert sequencing adapters into accessible chromatin, enabling mapping of regulatory regions across the genome. Additionally, the local distribution of Tn5 insertions contains information about transcription factor binding due to the visible depletion of insertions around sites bound by protein - known as footprints.

TOBIAS is a collection of command-line bioinformatics tools for performing footprinting analysis on ATAC-seq data, and includes:

• Correction of Tn5 insertion bias
• Calculation of footprint scores within regulatory regions
• Estimation of bound/unbound transcription factor binding sites
• Visualization of footprints within and across different conditions

For information on each tool, please see the wiki.

Installation

TOBIAS is written as a python package and can be quickly installed within a conda environment using:

$ git clone https://github.molgen.mpg.de/loosolab/TOBIAS
$ cd TOBIAS
$ conda env create -f snakemake_pipeline/environments/tobias.yaml
$ conda activate TOBIAS_ENV
$ python setup.py install

Please see the installation page for more info.

Usage

All tools are available through the command-line as TOBIAS <TOOLNAME>, for example:

$ TOBIAS ATACorrect
__________________________________________________________________________________________

                                   TOBIAS ~ ATACorrect
__________________________________________________________________________________________

ATACorrect corrects the cutsite-signal from ATAC-seq with regard to the underlying
sequence preference of Tn5 transposase.

Usage:
TOBIAS ATACorrect --bam <reads.bam> --genome <genome.fa> --peaks <peaks.bed>

Output files:
- <outdir>/<prefix>_uncorrected.bw
- <outdir>/<prefix>_bias.bw
- <outdir>/<prefix>_expected.bw
- <outdir>/<prefix>_corrected.bw
- <outdir>/<prefix>_atacorrect.pdf

(...)

Snakemake pipeline

You can run each TOBIAS tool independently or as part of a pipeline using the included snakemake workflow. Simply set the paths to required data within snakemake_pipeline/TOBIAS.config and run using:

$ cd snakemake_pipeline
$ conda activate TOBIAS_ENV
$ snakemake --snakefile TOBIAS.snake --configfile TOBIAS.config --cores [number of cores] --keep-going

For further info on setup, configfile and output, please consult the wiki.

License

This project is licensed under the MIT license.

Contact

Mette Bentsen (mette.bentsen (at) mpi-bn.mpg.de)