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Global prediction of chromatin accessibility using small-cell-number and single-cell RNA-seq.

Weiqiang Zhou | Zhicheng Ji | Weixiang Fang | Hongkai Ji
Nucleic acids research | 2019

Conventional high-throughput genomic technologies for mapping regulatory element activities in bulk samples such as ChIP-seq, DNase-seq and FAIRE-seq cannot analyze samples with small numbers of cells. The recently developed low-input and single-cell regulome mapping technologies such as ATAC-seq and single-cell ATAC-seq (scATAC-seq) allow analyses of small-cell-number and single-cell samples, but their signals remain highly discrete or noisy. Compared to these regulome mapping technologies, transcriptome profiling by RNA-seq is more widely used. Transcriptome data in single-cell and small-cell-number samples are more continuous and often less noisy. Here, we show that one can globally predict chromatin accessibility and infer regulatory element activities using RNA-seq. Genome-wide chromatin accessibility predicted by RNA-seq from 30 cells can offer better accuracy than ATAC-seq from 500 cells. Predictions based on single-cell RNA-seq (scRNA-seq) can more accurately reconstruct bulk chromatin accessibility than using scATAC-seq. Integrating ATAC-seq with predictions from RNA-seq increases the power and value of both methods. Thus, transcriptome-based prediction provides a new tool for decoding gene regulatory circuitry in samples with limited cell numbers.

Pubmed ID: 31428792

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NHGRI NIH HHS, United States
    Id: R01 HG006282
  • Agency: NHGRI NIH HHS, United States
    Id: R01 HG009518

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