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

ABSTRACT: 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.

SUBMITTER: Barry T

PROVIDER: S-EPMC8686614 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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

Barry Timothy T Wang Xuran X Morris John A JA Roeder Kathryn K Katsevich Eugene E

Genome biology 20211220 1

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 betwee ...[more]

PMID: 34930414

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