Identifying regulatory variants using multiome single-cell sequencing in prostate cell lines

Despite significant progresses, the genetic roles of regulatory elements in gene expression still remain largely unknown in prostate cells. Recent development in single cell sequencing has made it possible to combine ATAC-seq and RNA-seq to determine genome-wide linkages between chromatin accessibilities and gene expression. To test the feasibility of using single cell multiome sequencing in dissecting regulatory linkages between chromatin accessibilities and gene expressions, we applied 10X Multiome ATAC + Gene Expression platform to simultaneously encapsulate Tn5 transposase tagged nuclei from multiple prostate cell lines. Based on these multiomic data, we developed subsampling linkage analysis to identify linkage associations between open chromatin and gene expressions. Moreover, we implemented an innovative analytical method to investigate RNA expression alterations related to germline variant locus accessibilities at single cell levels, i.e., expression quantitate accessible loci (eQAL) analysis. Our data and methodology will complement traditional eQTL analysis and foresee more genetic applications aiming to clarify regulatory elements by single cell sequencing. Overall design: Multiomic profilings in human prostate cell lines were captured using 10x Multiome ATAC + Gene Expression assay, and targeted hybridization enrichment was further used to collect signals on eQTL locus.