‘These footprints are leading us nowhere!’ investigation of the usage of footprinting analysis for ATAC-seq data to find regulatory elements

Abstract

ATAC-sequencing is a popular method to measure and sequence the accessible parts of the DNA in a cell. The accessible parts of the DNA are called open chromatin. The closed chromatin is the part of the DNA that is inaccessible. The closed parts of the DNA are bound to nucleosomes, the spool-like proteins that keep DNA organized and compact. These parts are difficult to be accessed by any proteins, and so they can not be reached by the proteins that transcribe DNA and make the cell function as it does. The parts that are not bound to anything, the open parts, play an important role in how the cell behaves. When smaller proteins than nucleosomes are bound to the DNA, this is visible in the ATAC-seq results. These small proteins play a huge part in the behaviour of a cell. A way of analyzing these small bound proteins in the ATAC-seq data is by doing a footprinting analysis. A footprinting analysis could give a lot of information about the behaviour of a cell. When this analysis is done on a diseased cell, information could be obtained about which parts of the DNA and which bound proteins cause a cell to be diseased. This is valuable information for attempts to cure many genetic diseases. Analyzing ATAC-seq data to learn about cell behaviour is still difficult. This paper examines the use of the footprinting analysis on ATAC-seq data by comparing it to other methods used to investigate cell regulation.