Multicenter integrated analysis of noncoding CRISPRi screens

Mar 20, 2024Nature methods

Combined analysis of CRISPR interference screens targeting noncoding DNA from multiple centers

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Abstract

The ENCODE4 Functional Characterization Centers conducted 108 screens in human cell lines, comprising >540,000 perturbations across 24.85 megabases of the genome.

  • Pooled, noncoding CRISPR screens may enhance the study of gene regulatory mechanisms.
  • Guidelines were established for screening noncoding elements with CRISPR interference, focusing on detecting CREs with variable transcriptional effects.
  • CASA was identified as the analysis tool that produces the most conservative calls for CREs and is resilient to low-specificity single guide RNA artifacts.
  • A subtle DNA strand bias was observed for CRISPRi in transcribed regions, which may impact screen design and analysis.
  • An accessible data resource with predesigned single guide RNAs is available for targeting 3,275,697 ENCODE SCREEN candidate CREs.

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