NEAT-seq

NEAT-seq profiles nuclear protein epitope abundance, chromatin accessibility, and the transcriptome in single cells to jointly characterize transcription factor activity and regulatory interactions between chromatin and gene expression.


Key Features:

  • Multi-modal single-cell sequencing: Simultaneously sequences nuclear protein epitope abundance, chromatin accessibility, and the transcriptome in the same single cells.
  • Intra-nuclear protein epitope profiling: Profiles intra-nuclear proteins including transcription factors (TFs) via nuclear protein epitope abundance measurements.
  • Chromatin accessibility measurement: Measures chromatin accessibility to assess DNA accessibility states.
  • Transcriptome profiling: Performs single-cell transcriptome sequencing to quantify gene expression and RNA synthesis.
  • Integrated TF–chromatin–transcriptome analysis: Integrates measurements to explore interplay between transcription factors (TFs), chromatin dynamics, and transcriptomic outputs.
  • Stage-resolved regulation analysis: Enables analysis across stages from DNA accessibility to RNA synthesis, linking chromatin state to transcriptomic output.
  • Application to CD4 memory T cells: Has been applied to CD4 memory T cells using a panel of master transcription factors to interrogate T cell differentiation and function.
  • Detection of TF regulatory modulation: Identifies TFs whose regulatory activities are modulated by transcription, translation, and chromatin binding dynamics.
  • Variant-to-function mapping: Links noncoding genome-wide association study single-nucleotide polymorphisms (SNPs) within regulatory motifs, such as a GATA motif, to effects on target gene regulation including GATA3.

Scientific Applications:

  • Regulatory mechanism dissection: Dissects regulatory networks coupling TF activity, chromatin dynamics, and gene expression at single-cell resolution.
  • Immunology and T cell differentiation: Profiles CD4 memory T cell subsets and master transcription factors governing differentiation and function.
  • Genetic variant functionalization: Maps noncoding GWAS SNPs in motifs (e.g., a GATA motif) to functional impacts on target genes such as GATA3.

Methodology:

The provided description does not specify computational methods, algorithms, or file formats.

Topics

Details

License:
Not licensed
Cost:
Free of charge
Tool Type:
library
Operating Systems:
Mac, Linux, Windows
Programming Languages:
R, C++
Added:
8/27/2022
Last Updated:
11/24/2024

Operations

Publications

Chen AF, Parks B, Kathiria AS, Ober-Reynolds B, Goronzy JJ, Greenleaf WJ. NEAT-seq: simultaneous profiling of intra-nuclear proteins, chromatin accessibility and gene expression in single cells. Nature Methods. 2022;19(5):547-553. doi:10.1038/s41592-022-01461-y. PMID:35501385. PMCID:PMC11192021.

PMID: 35501385
Funding: - U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute: P50HG007735, UM1HG009442 - U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences: F32GM135996 - Division of Intramural Research, National Institute of Allergy and Infectious Diseases: U19AI057266