Uniform quantification of single-nucleus ATAC-seq data with Paired-Insertion Counting (PIC) and a model-based insertion rate estimator

Abstract Existing approaches to scoring single-nucleus assay for transposase-accessible chromatin with sequencing (snATAC-seq) feature matrices from sequencing reads are inconsistent, affecting downstream analyses and displaying artifacts. We show that, even with sparse single-cell data, quantitative counts are informative for estimating the regulatory state of a cell, which calls for a consistent treatment. We propose Paired-Insertion Counting as a uniform method for snATAC-seq feature characterization and provide a probability model for inferring latent insertion dynamics from snATAC-seq count matrices.