Pooled genetic screens with image‐based profiling. Issue 11 (11th November 2022)

• Record Type: Journal Article
• Authors: Walton, Russell T; Singh, Avtar; Blainey, Paul C
• Is Part Of: Molecular systems biology. Volume 18:Issue 11(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-11-11
• Subjects: morphological profiling -- multiplexed imaging -- optical microscopy profiling -- optical screening -- pooled genetic screening; Molecular biology -- Periodicals; Systems biology -- Periodicals; 572.8
• DOI: 10.15252/msb.202110768
• Languages: English
• ISSNs: 1744-4292

Abstract

Abstract: Spatial structure in biology, spanning molecular, organellular, cellular, tissue, and organismal scales, is encoded through a combination of genetic and epigenetic factors in individual cells. Microscopy remains the most direct approach to exploring the intricate spatial complexity defining biological systems and the structured dynamic responses of these systems to perturbations. Genetic screens with deep single‐cell profiling via image features or gene expression programs have the capacity to show how biological systems work in detail by cataloging many cellular phenotypes with one experimental assay. Microscopy‐based cellular profiling provides information complementary to next‐generation sequencing (NGS) profiling and has only recently become compatible with large‐scale genetic screens. Optical screening now offers the scale needed for systematic characterization and is poised for further scale‐up. We discuss how these methodologies, together with emerging technologies for genetic perturbation and microscopy‐based multiplexed molecular phenotyping, are powering new approaches to reveal genotype–phenotype relationships. Abstract : This review discusses the technological advances that enable studies of genotype‐to‐phenotype relationships with microscopy‐based imaging and proposes a roadmap for the future development and application of pooled profiling screens with image‐based phenotypes.