ArchR: An integrative and scalable software package for single-cell chromatin accessibility analysis

The advent of large-scale single-cell chromatin accessibility profiling has accelerated our ability to map gene regulatory landscapes, but has outpaced the development of scalable software to rapidly extract biological meaning from these data. Here we present a software suite for single-cell analysis of regulatory chromatin in R (ArchR; www.ArchRProject.com) that enables fast and comprehensive analysis of single-cell chromatin accessibility data. ArchR provides an intuitive, user-focused interface for complex single-cell analyses including doublet removal, single-cell clustering and cell type identification, unified peak set generation, cellular trajectory identification, DNA element to gene linkage, transcription factor footprinting, mRNA expression level prediction from chromatin accessibility, and multi-omic integration with scRNA-seq. Enabling the analysis of over 1.2 million single cells within 8 hours on a standard Unix laptop, ArchR is a comprehensive analytical suite for end-to-end analysis of single-cell chromatin accessibility data that will accelerate the understanding of gene regulation at the resolution of individual cells. 10x Genomics single-nucleus ATAC-seq and bulk ATAC-seq data obtained from 10 different cell lines. These cell lines include K562, Jurkat, THP1, GM12878, MCF7, MCF10A, HeLa, HT1080, T24, and 293T. In the context of 10x Genomics snATAC-seq, all cell lines were mixed together to enable detection of multiplet droplets based on genotype.大规模单细胞染色质可及性图谱分析技术的问世，极大提升了我们绘制基因调控景观的能力，但该技术带来的数据量增速已远超可扩展型软件的开发进度，导致无法快速从这些数据中提取生物学内涵。本文我们推出一款基于R语言的调控染色质单细胞分析软件套件（ArchR；www.ArchRProject.com），可实现单细胞染色质可及性数据的快速且全面分析。ArchR提供了直观且面向用户的交互界面，可支持各类复杂的单细胞分析任务，包括双细胞去除、单细胞聚类与细胞类型鉴定、统一峰集生成、细胞轨迹识别、DNA元件-基因关联分析、转录因子足迹分析、基于染色质可及性的mRNA表达水平预测，以及与单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）的多组学整合。在标准Unix笔记本电脑环境下，ArchR可在8小时内完成超120万个单细胞的分析工作，是一款可实现单细胞染色质可及性数据端到端分析的综合性分析套件，将助力在单细胞分辨率下解析基因调控机制的研究。本数据集包含10x Genomics平台产生的10种不同细胞系的单核ATAC-seq（single-nucleus Assay for Transposase-Accessible Chromatin using sequencing, snATAC-seq）与批量ATAC-seq数据，涉及的细胞系包括K562、Jurkat、THP1、GM12878、MCF7、MCF10A、HeLa、HT1080、T24及293T。在10x Genomics snATAC-seq实验中，所有细胞系被混合，以实现基于基因型的多重液滴检测。