Protocol for single-nucleus ATAC sequencing and bioinformatic analysis in frozen human brain tissue

STAR Protoc. 2022 Jun 17;3(3):101491. doi: 10.1016/j.xpro.2022.101491. eCollection 2022 Sep 16.

Abstract

Single-nucleus ATAC sequencing (snATAC-seq) employs a hyperactive Tn5 transposase to gain precise information about the cis-regulatory elements in specific cell types. However, the standard protocol of snATAC-seq is not optimized for all tissues, including the brain. Here, we present a modified protocol for single-nuclei isolation from postmortem frozen human brain tissue, followed by snATAC-seq library preparation and sequencing. We also describe an integrated bioinformatics analysis pipeline using an R package (ArchRtoSignac) to robustly analyze snATAC-seq data. For complete details on the use and execution of this protocol, please refer to Morabito et al. (2021).

Keywords: Bioinformatics; Genomics; Health Sciences; Neuroscience; Sequence analysis; Sequencing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Brain
  • Chromatin
  • Computational Biology*
  • High-Throughput Nucleotide Sequencing* / methods
  • Humans
  • Sequence Analysis, DNA / methods

Substances

  • Chromatin