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bioRxiv · 10.1101/2022.04.25.489439

SeATAC: a tool for exploring the chromatin landscape and the role of pioneer factors

Dsouza, N.·Gong, W.·Garry, D.
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Abstract

The position of the nucleosome and chromatin packaging in eukaryotic genomes govern gene regulation and cellular functions. Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) is an efficient and precise method for revealing chromatin accessibility across the genome. However, there is no method that is specifically designed for detecting differential chromatin accessibility using ATAC-seq datasets. In this study, we developed a bioinformatics tool called SeATAC, that used a conditional variational autoencoder (CVAE) model to learn the latent representation of ATAC-seq V-plots, and to estimate the statistically differential chromatin accessibility. We demonstrated that SeATAC outperformed MACS2 and NucleoATAC on four separate tasks including: (1) detection of differential V-plots; (2) definition of nucleosome positions; (3) detection of nucleosome changes and (4) designation of transcriptional factor binding sites (TFBS) with differential chromatin accessibility. By applying SeATAC to several pioneer factor induced differentiation or reprogramming ATAC-seq datasets, we found that induction of these pioneer factors not only relaxed the closed chromatin but also decreased the chromatin accessibility of 20% - 30% of their target sites. These two groups of TF binding sites were characterized by different genomic distribution and histone marks. Here, we present SeATAC as a novel tool to accurately reveal the genomic regions with differential chromatin accessibility from ATAC-seq data.

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Dsouza, N., Gong, W., Garry, D.. 2022-04-26. SeATAC: a tool for exploring the chromatin landscape and the role of pioneer factors. https://doi.org/10.1101/2022.04.25.489439

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