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scifi-ATAC-seq: massive-scale single-cell chromatin accessibility sequencing using combinatorial fluidic indexing.

Xuan Zhang1, Alexandre P Marand1,2, Haidong Yan1

  • 1Department of Genetics, University of Georgia, Athens, GA, USA.

Genome Biology
|April 8, 2024
PubMed
Summary

We developed scifi-ATAC-seq, a new method for single-cell ATAC sequencing. This technique significantly increases throughput, enabling genome-wide analysis of regulatory elements in many more cells and samples.

Keywords:
ATAC-seqChromatin accessibilityCombinatorial fluidic indexingMassive-scaleSingle-cell

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Area of Science:

  • Genomics
  • Molecular Biology
  • Bioinformatics

Background:

  • Single-cell ATAC sequencing (scATAC-seq) is crucial for identifying cis-regulatory elements at single-cell resolution.
  • Existing scATAC-seq methods face limitations in throughput and cost, hindering large-scale studies.

Purpose of the Study:

  • To introduce scifi-ATAC-seq, a novel, high-throughput single-cell ATAC sequencing technique.
  • To overcome the throughput and cost limitations of current scATAC-seq methods.

Main Methods:

  • scifi-ATAC-seq combines combinatorial fluidic indexing with droplet-based single-cell ATAC sequencing.
  • A barcoded Tn5 pre-indexing step is integrated with the 10X Genomics platform.

Main Results:

  • scifi-ATAC-seq enables indexing of up to 200,000 nuclei in a single reaction.
  • This represents an approximately 20-fold increase in throughput compared to standard 10X Genomics workflows.

Conclusions:

  • scifi-ATAC-seq substantially enhances the scalability of single-cell ATAC sequencing.
  • This advancement facilitates comprehensive genome-wide analysis of regulatory elements across numerous cells and samples.