A generic reference defined by consensus peaks for single-cell ATAC-seq data analysis

Area of Science:

• Genomics
• Molecular Biology
• Bioinformatics

Background:

• Single-cell ATAC-seq (scATAC-seq) advances gene regulation studies.
• Lack of a generic ATAC-seq reference hinders single-cell analysis and cell atlas development.

Purpose of the Study:

• To create a universal chromatin accessibility reference for scATAC-seq data.
• To enhance cell annotation and rare cell type identification in single-cell studies.

Main Methods:

• Aggregated 1.4 million consensus peaks (cPeaks) from 624 bulk ATAC-seq datasets.
• Utilized a deep neural network to expand cPeaks coverage.
• Validated cPeaks performance against existing methods in scATAC-seq analyses.

Main Results:

• Developed cPeaks, a robust chromatin accessibility reference.
• Demonstrated superior performance of cPeaks in scATAC-seq cell annotation and rare cell identification.
• Showcased cPeaks' utility in studying chromatin dynamics during differentiation and tumor progression.

Conclusions:

• cPeaks provide a consistent and comprehensive reference for chromatin accessibility.
• This reference promotes cross-dataset consistency and accelerates biological discoveries in gene regulation.
• cPeaks are crucial for advancing single-cell genomics and cell atlas initiatives.