Pooled genetic screens with image‐based profiling

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...

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Main Authors: Russell T Walton, Avtar Singh, Paul C Blainey
Format: Article
Language:English
Published: Springer Nature 2022-11-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.15252/msb.202110768
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author Russell T Walton
Avtar Singh
Paul C Blainey
author_facet Russell T Walton
Avtar Singh
Paul C Blainey
author_sort Russell T Walton
collection DOAJ
description 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.
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institution Kabale University
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publishDate 2022-11-01
publisher Springer Nature
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series Molecular Systems Biology
spelling doaj-art-d0dbc8fc7466427390ba183d21c1a17d2025-08-24T12:01:01ZengSpringer NatureMolecular Systems Biology1744-42922022-11-01181112310.15252/msb.202110768Pooled genetic screens with image‐based profilingRussell T Walton0Avtar Singh1Paul C Blainey2Broad Institute of MIT and HarvardBroad Institute of MIT and HarvardBroad Institute of MIT and HarvardAbstract 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.https://doi.org/10.15252/msb.202110768morphological profilingmultiplexed imagingoptical microscopy profilingoptical screeningpooled genetic screening
spellingShingle Russell T Walton
Avtar Singh
Paul C Blainey
Pooled genetic screens with image‐based profiling
Molecular Systems Biology
morphological profiling
multiplexed imaging
optical microscopy profiling
optical screening
pooled genetic screening
title Pooled genetic screens with image‐based profiling
title_full Pooled genetic screens with image‐based profiling
title_fullStr Pooled genetic screens with image‐based profiling
title_full_unstemmed Pooled genetic screens with image‐based profiling
title_short Pooled genetic screens with image‐based profiling
title_sort pooled genetic screens with image based profiling
topic morphological profiling
multiplexed imaging
optical microscopy profiling
optical screening
pooled genetic screening
url https://doi.org/10.15252/msb.202110768
work_keys_str_mv AT russelltwalton pooledgeneticscreenswithimagebasedprofiling
AT avtarsingh pooledgeneticscreenswithimagebasedprofiling
AT paulcblainey pooledgeneticscreenswithimagebasedprofiling