4.5 Article

SCEPTRE improves calibration and sensitivity in single-cell CRISPR screen analysis

Journal

GENOME BIOLOGY
Volume 22, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s13059-021-02545-2

Keywords

-

Funding

  1. National Institute of Mental Health (NIMH) [R01MH123184]
  2. SFARI [575547]
  3. National Science Foundation [ACI-1548562]
  4. NSF, at the Pittsburgh Supercomputing Center (PSC) [ACI-1445606]

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SCEPTRE is a method that analyzes single-cell perturbation screens through conditional resampling, effectively addressing calibration issues in these screens and yielding new regulatory relationships supported by orthogonal biological evidence.
Single-cell CRISPR screens are a promising biotechnology for mapping regulatory elements to target genes at genome-wide scale. However, technical factors like sequencing depth impact not only expression measurement but also perturbation detection, creating a confounding effect. We demonstrate on two single-cell CRISPR screens how these challenges cause calibration issues. We propose SCEPTRE: analysis of single-cell perturbation screens via conditional resampling, which infers associations between perturbations and expression by resampling the former according to a working model for perturbation detection probability in each cell. SCEPTRE demonstrates very good calibration and sensitivity on CRISPR screen data, yielding hundreds of new regulatory relationships supported by orthogonal biological evidence.

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