scReadSim: a single-cell multi-omics read simulator

Abstract

Benchmarking single-cell RNA-seq (scRNA-seq) and single-cell ATAC-seq (scATAC-seq) computational tools demands simulators to generate realistic sequencing reads. However, none of the few read simulators aim to mimic real data. To fill this gap, we introduce scReadSim, a single-cell RNA-seq and ATAC-seq read simulator that allows user-specified ground truths and generates synthetic sequencing reads (in FASTQ and BAM formats) by mimicking real data. At both read-sequence and read-count levels, scReadSim mimics real scRNA-seq and scATAC-seq data. Moreover, scReadSim provides ground truths, including unique molecular identifier counts for scRNA-seq and open chromatin regions for scATAC-seq. In particular, scReadSim allows users to design cell-type-specific ground-truth open chromatin regions for scATAC-seq data generation. In benchmark applications of scReadSim, we show that cell-ranger is a preferred scRNA-seq UMI deduplication tool, and HMMRATAC and MACS3 achieve top performance in scATAC-seq peak calling.