Delivering Robust Candidates to the Drug Pipeline through Computational Analysis of Arrayed CRISPR Screens

SLAS Discov. 2020 Jul;25(6):646-654. doi: 10.1177/2472555220921132. Epub 2020 May 12.

Abstract

Genome-wide arrayed CRISPR screening is a powerful method for drug target identification as it enables exploration of the effect of individual gene perturbations using diverse highly multiplexed functional and phenotypic assays. Using high-content imaging, we can measure changes in biomarker expression, intracellular localization, and cell morphology. Here we present the computational pipeline we have developed to support the analysis and interpretation of arrayed CRISPR screens. This includes evaluating the quality of guide RNA libraries, performing image analysis, evaluating assay results quality, data processing, hit identification, ranking, visualization, and biological interpretation.

Keywords: arrayed CRISPR screening; bioinformatics; data analysis; high-content imaging; target identification.

MeSH terms

  • Biomarkers / analysis
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics*
  • Computational Biology*
  • Drug Discovery
  • Gene Library
  • Genome, Human / genetics
  • High-Throughput Screening Assays / trends*
  • Humans
  • Molecular Imaging / trends
  • RNA, Guide, CRISPR-Cas Systems / genetics*

Substances

  • Biomarkers
  • RNA, Guide, CRISPR-Cas Systems