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Related Concept Videos

Genetic Screens02:46

Genetic Screens

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Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing  genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
5.6K

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Related Experiment Video

Updated: Jan 19, 2026

A Combinatorial Single-cell Approach to Characterize the Molecular and Immunophenotypic Heterogeneity of Human Stem and Progenitor Populations
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High-throughput genome-wide phenotypic screening via immunomagnetic cell sorting.

Barbara Mair1, Peter M Aldridge2, Randy S Atwal2

  • 1Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.

Nature Biomedical Engineering
|September 25, 2019
PubMed
Summary

This study introduces a rapid, high-throughput immunomagnetic cell sorting method for CRISPR-Cas9 genetic screens. The novel technique efficiently identifies genetic modulators, like QPCTL, impacting cell surface targets such as CD47.

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Cell Surface Receptor Identification Using Genome-Scale CRISPR/Cas9 Genetic Screens
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Cell Surface Receptor Identification Using Genome-Scale CRISPR/Cas9 Genetic Screens

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Area of Science:

  • Genomics
  • Cell Biology
  • Biotechnology

Background:

  • Genome-scale functional genetic screens identify key genetic regulators of cellular phenotypes.
  • Current methods involving cell sorting are time-consuming, costly, and can reduce cell viability.
  • High-throughput screening is crucial for advancing fields like immuno-oncology.

Purpose of the Study:

  • To develop a rapid, scalable, and high-throughput method for loss-of-function phenotypic screening.
  • To overcome the limitations of existing cell sorting techniques in genetic screens.
  • To identify novel genetic regulators of cell surface protein display.

Main Methods:

  • Utilized immunomagnetic cell sorting integrated with a microfluidic chip for CRISPR-Cas9 screening.
  • Processed over 10^8 cells in under 1 hour, exceeding fluorescence-activated cell sorting throughput.
  • Maintained high cell viability throughout the genome-wide screen.

Main Results:

  • Successfully identified modulators of CD47 display, a key target in immuno-oncology.
  • Validated glutaminyl cyclase (QPCTL) as a top hit, demonstrating its role in modifying CD47.
  • Achieved significantly higher throughput than fluorescence-activated cell sorting while preserving cell health.

Conclusions:

  • The novel immunomagnetic cell sorting method offers a rapid and scalable solution for high-throughput genetic screening.
  • This technique bridges the gap between traditional cell sorting methods and higher-throughput systems.
  • The findings provide a new tool for discovering genetic regulators of important cell surface targets like CD47.