10x Genomics, Inc.
SYSTEMS AND METHODS FOR IDENTIFYING DIFFERENTIAL ACCESSIBILITY OF GENE REGULATORY ELEMENTS AT SINGLE CELL RESOLUTION

Abstract:

A method for ascertaining differential accessibility of (TF) binding motifs in open chromatin regions of cells, comprising receiving a cell barcode genomic sequence dataset; aligning each of a plurality of fragment sequence reads to a reference sequence; identifying peaks defined by the aligned plurality of fragment sequence reads; generating a peak-barcode matrix that is comprised of peaks for each cell barcode; clustering cells with peaks having similar chromatin accessibility profiles into a cell cluster to form one or more cell clusters; generating a TF barcode matrix that maps each peak in the peak-barcode matrix to one or more given TF binding motif(s); performing a differential accessibility analysis, wherein the analysis identifies differences in accessibility of peaks and TF binding motifs associated with each identified cell cluster relative to all other identified cell clusters; and generating an output of one or more refined cell clusters based on the differential accessibility analysis.