scTELL: A Single-Cell ATAC-seq Tool for Locus-Specific Transposable Element Identification in Chromatin Accessibility

Transposable elements (TEs) are essential genomic entities that play the roles of eukaryotic genome regulators and are involved in controlling gene expression patterns, cell-type specialization, and diseases. Recent improvements of single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) have enhanced the chromatin accessibility investigation with cell type specificity. However, existing techniques do not address the locus-specific activity of TEs. Here, we present scTELL (single-cell Transposable Element Locus-Level analysis), a bioinformatics tool for the analysis of TE accessibility at the single-cell level. Based on the distribution of scATAC-seq peaks, scTELL enablesusers with the ability to analyze the locus-specific TE activity in relation to cellular heterogeneity as well as changes in regulatory dynamics occurring across different samples. Through scTELL, we mapped TEs in both quiescent healthy peripheral blood mononuclear cells (PBMC) and in cancer cells: clear cell renal cell carcinoma (ccRCC) and breast cancer (BRCA), defining cell type-specific and tumor-specific TE groups. L1PA2 expression in ccRCC consistently exhibited the locus-specific pattern and predicted cancer progression and patient survival. Likewise, in BRCA, scTELL identified prognostic TE loci whose accessibility profiles are associated with patient survival. These results reveal that TEs can alter tumor heterogeneity and point to TEs as a prognostic factor. The scTELL framework provides a new way of determining the regulatory roles of TEs in various biological settings and improving the knowledge of the role of TEs in both normal and pathological cellular conditions.