Cellsnp-lite: an efficient tool for genotyping single cells

Abstract

SummarySingle-cell sequencing is an increasingly used technology and has promising applications in basic research and clinical translations. However, genotyping methods developed for bulk sequencing data have not been well adapted for single-cell data, in terms of both computational parallelization and simplified user interface. Here we introduce a software, cellsnp-lite, implemented in C/C++ and based on well supported package htslib, for genotyping in single-cell sequencing data for both droplet and well based platforms. On various experimental data sets, it shows substantial improvement in computational speed and memory efficiency with retaining highly concordant results compared to existing methods. Cellsnp-lite therefore lightens the genetic analysis for increasingly large single-cell data.AvailabilityThe source code is freely available at https://github.com/single-cell-genetics/cellsnp-lite.Contactyuanhua@hku.hk

MQuad enables clonal substructure discovery using single cell mitochondrial variants

“…This means that cell lineage information can be discovered with virtually no additional experimental cost. We make the MQuad source code and tool publicly available, and the program is designed to work seamlessly with other recently published tools, cellsnp-lite 18 and vireo 19 . Our analysis shows that leveraging mtDNA mutations can decipher not only tumor clonal dynamics but also resolve clonal substructure that may not be detectable based on nuclear DNA alone.…”

“…MQuad is a computational method for detecting clone discriminative mitochondrial variants. It is tailored to work seamlessly with cellsnp-lite 18 and vireoSNP 19 to create an automated end-to-end pipeline for single cell clonal discovery using mitochondrial variants (Fig. 1a).…”

“…The tailored variant detection pipeline can be briefly divided into 3 major steps: Firstly, raw reads from BAM files are piled up using cellSNP-lite (v1.2.0) 18 . This generates a SNP-by-cell matrix in the form of a VCF file or sparse matrices of each cell's AD and DP at each .…”

anonymizeBAM: Versatile anonymization of human sequence data for open data sharing

“…Genotype-informative base coverage was summarized per cell over 7.4 million common variants (AF>5% in the 1000 genomes project phase 3) with cellsnp-lite 17 (v 1.2.0) using the --UMItag None --minCOUNT 10 settings. The resulting sparse VCF file was loaded into vireo 18 (v 0.4.2) and donor deconvolution performed using the appropriate --nDonor flag (n = 2 for scATAC, n=5 for 10x scRNAseq and n=6 for Smart-seq3).…”

“…To illustrate the effectiveness of our program, we analyzed a recently published dataset of single-cell RNA sequencing (scRNA-seq) data generated from five equally abundant cell lines 14 via the popular 10x Genomics 15 protocol. After preprocessing the raw data with zUMIs 16 , we summarized SNP coverage and assigned the 2,937 high-quality (>= 66% exonic, >= 25,000 reads) cells to their donor of origin using cellsnp-lite 17 and vireo 18 . Clearly, each of the cells in the main clusters could be assigned to a single donor corresponding to one of the cell lines ( Figure 2a ).…”