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Reducing batch effects in single cell chromatin accessibility measurements by pooled transposition with MULTI-ATAC
Daniel N Conrad1, Kiet T Phong1, Ekaterina Korotkevich2
1Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
Biorxiv : the Preprint Server for Biology
|March 3, 2025
Summary
Large-scale single-cell ATAC sequencing (scATAC-seq) is prone to batch effects. We developed MULTI-ATAC, a novel multiplexing method that pools samples before transposition to eliminate these effects and enable scalable, batch-free experiments.
Area of Science:
- Single-cell genomics
- Epigenetics
- Drug discovery
Background:
- Large-scale single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) faces challenges including high costs, lengthy protocols, and batch effects.
- Existing sample multiplexing technologies do not fully address batch effects arising from parallel transposition reactions.
Purpose of the Study:
- To address batch effects in scATAC-seq caused by variable nuclei-to-Tn5 ratios.
- To develop a scalable and batch-free multiplexing method for scATAC-seq.
Main Methods:
- Developed MULTI-ATAC, a method that pools samples prior to the transposition step.
- Validated MULTI-ATAC using a 96-plex multiomic drug assay on immune cells.
- Assessed sample classification accuracy and doublet detection.
Main Results:
- MULTI-ATAC effectively eliminates batch effects stemming from variable nuclei-to-Tn5 ratios.
- The method achieves high accuracy in sample classification and doublet detection.
- A 96-plex drug assay revealed numerous drug-responsive chromatin regions and cell-type specific effects.
Conclusions:
- MULTI-ATAC enables batch-free and scalable scATAC-seq workflows.
- The method provides deeper insights into complex biological processes and therapeutic targets.
- MULTI-ATAC is powerful for multiomic drug screening and understanding epigenetic regulation.
