DETECTING DIFFERENTIAL TRANSCRIPTION FACTOR BINDING BASED ON SINGLE-CELL DNA ACCESSIBILITY
by John Lin
Abstract – Common genetic diseases—systemic diseases that are caused by thousands of mutations—affect millions of people around the world. Many of these mutations fall within regulatory regions. While the mutations associated with these diseases are widely known, the link between these mutations and their role in disease pathogenicity has largely gone undiscovered. This study harnesses single cell ATAC-seq data to differentiate bound and unbound sites in regulatory regions, serving as a first step to understanding these diseases. By computing observed and expected cuts for footprint regions, this study finds that regions with lower observed cuts than expected cuts conferred to protection from sequencing enzymes, indicating the presence of a bound transcription factor. In contrast, regions with higher observed cuts than expected indicate the absence of protection from sequencing enzymes, suggesting an absence of a bound transcription factor. In distinguishing between bound and unbound transcription factors, this study paves the way for using single cell ATAC-seq to understand common diseases by identifying the cell types and changes in transcription factor binding caused by mutations.