Prediction of Chromatin Accessibility in Gene-Regulatory Regions from Transcriptomics Data.

ABSTRACT

The epigenetics landscape of cells plays a key role in the establishment of cell-type specific gene expression programs characteristic of different cellular phenotypes. Different experimental procedures have been developed to obtain insights into the accessible chromatin landscape including DNase-seq, FAIRE-seq and ATAC-seq. However, current downstream computational tools fail to reliably determine regulatory region accessibility from the analysis of these experimental data. In particular, currently available peak calling algorithms are very sensitive to their parameter settings and show highly heterogeneous results, which hampers a trustworthy identification of accessible chromatin regions. Here, we present a novel method that predicts accessible and, more importantly, inaccessible gene-regulatory chromatin regions solely relying on transcriptomics data, which complements and improves the results of currently available computational methods for chromatin accessibility assays. We trained a hierarchical classification tree model on publicly available transcriptomics and DNase-seq data and assessed the predictive power of the model in six gold standard datasets. Our method increases precision and recall compared to traditional peak calling algorithms, while its usage is not limited to the prediction of accessible and inaccessible gene-regulatory chromatin regions, but constitutes a helpful tool for optimizing the parameter settings of peak calling methods in a cell type specific manner.