Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Genetic Screens02:46

Genetic Screens

5.7K
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...
5.7K
What is Population Genetics?01:25

What is Population Genetics?

64.7K
A population is composed of members of the same species that simultaneously live and interact in the same area. When individuals in a population breed, they pass down their genes to their offspring. Many of these genes are polymorphic, meaning that they occur in multiple variants. Such variations of a gene are referred to as alleles. The collective set of all the alleles within a population is known as the gene pool.
64.7K
Mutation, Gene Flow, and Genetic Drift01:09

Mutation, Gene Flow, and Genetic Drift

64.1K
In a population that is not at Hardy-Weinberg equilibrium, the frequency of alleles changes over time. Therefore, any deviations from the five conditions of Hardy-Weinberg equilibrium can alter the genetic variation of a given population. Conditions that change the genetic variability of a population include mutations, natural selection, non-random mating, gene flow, and genetic drift (small population size).
64.1K
Genetics of Speciation02:16

Genetics of Speciation

21.0K
Speciation is the evolutionary process resulting in the formation of new, distinct species—groups of reproductively isolated populations.
21.0K
Leveling Effect01:29

Leveling Effect

1.4K
In acid-base chemistry, the leveling effect refers to the limitation imposed by the solvent on the strength of acids and bases in solution. When a base stronger than the solvent's conjugate base is used, it deprotonates the solvent until the base is entirely consumed, making it ineffective against weaker acids. Conversely, an acid stronger than the solvent's conjugate acid protonates the solvent until the acid is depleted, rendering it ineffective against weaker bases. Essentially, the...
1.4K
What is Genetic Engineering?00:49

What is Genetic Engineering?

80.1K
Overview
80.1K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

FDA-approved fulvestrant-induced CAR phase separation enables precise control of CAR T antitumor function.

Cell stem cell·2026
Same author

Mapping the dialogue: Decoding alveolar stem-niche interactions.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same author

Leveraging tumor dynamics to discover mutations influencing progression and treatment response for precision oncology.

Genome medicine·2026
Same author

Identification of highly expressed genes and efficient core promoters specific to buffalo skeletal muscles.

Archives animal breeding·2026
Same author

RNA sequencing reveals lncRNAs that specifically regulate unsaturated fatty acid generation in buffaloes.

Archives animal breeding·2026
Same author

Multiplexed perturbation enables scalable pooled screens.

Nature methods·2026

Related Experiment Video

Updated: Jan 29, 2026

Pooled CRISPR-Based Genetic Screens in Mammalian Cells
09:05

Pooled CRISPR-Based Genetic Screens in Mammalian Cells

Published on: September 4, 2019

23.2K

Tracing cellular heterogeneity in pooled genetic screens via multi-level barcoding.

Michael Boettcher1, Sergio Covarrubias1, Anne Biton2,3

  • 1Department of Microbiology and Immunology, UCSF Diabetes Center, University of California, San Francisco, San Francisco, CA, 94143, USA.

BMC Genomics
|February 8, 2019
PubMed
Summary

Cellular heterogeneity significantly impacts pooled CRISPR screens. Our multi-level barcoding method reveals how clonal cell line variations in growth and response skew genetic screen results.

Keywords:
CRISPRClonal heterogeneityGenome editingScreening

More Related Videos

Competitive Genomic Screens of Barcoded Yeast Libraries
11:59

Competitive Genomic Screens of Barcoded Yeast Libraries

Published on: August 11, 2011

18.8K
Multi-enzyme Screening Using a High-throughput Genetic Enzyme Screening System
08:10

Multi-enzyme Screening Using a High-throughput Genetic Enzyme Screening System

Published on: August 8, 2016

9.3K

Related Experiment Videos

Last Updated: Jan 29, 2026

Pooled CRISPR-Based Genetic Screens in Mammalian Cells
09:05

Pooled CRISPR-Based Genetic Screens in Mammalian Cells

Published on: September 4, 2019

23.2K
Competitive Genomic Screens of Barcoded Yeast Libraries
11:59

Competitive Genomic Screens of Barcoded Yeast Libraries

Published on: August 11, 2011

18.8K
Multi-enzyme Screening Using a High-throughput Genetic Enzyme Screening System
08:10

Multi-enzyme Screening Using a High-throughput Genetic Enzyme Screening System

Published on: August 8, 2016

9.3K

Area of Science:

  • Genomics
  • Molecular Biology
  • Cell Biology

Background:

  • Pooled loss- and gain-of-function CRISPR screening is widely used for mammalian gene function studies.
  • Existing methods often overlook cellular heterogeneity, analyzing bulk cell populations instead of individual clonal responses.

Purpose of the Study:

  • To develop and validate a novel barcoding approach to account for cellular heterogeneity in CRISPR screens.
  • To investigate the impact of clonal cell line variations on pooled genetic screen outcomes.

Main Methods:

  • Development of multi-level barcoded sgRNA libraries for tracing multiple clonal Cas9 cell lines.
  • Application of barcoding to monitor growth kinetics and treatment responses under identical conditions.
  • Enabling in-sample replication and sub-clonal lineage tracing within cells expressing the same sgRNA.

Main Results:

  • The developed method allows for the simultaneous monitoring of multiplexed clonal cell lines.
  • It enables precise tracking of growth kinetics and treatment responses across different clonal lines.
  • Demonstrated how clonal heterogeneity in growth and response can significantly affect pooled screen analyses.

Conclusions:

  • Cellular heterogeneity, specifically variations in growth kinetics and treatment response among clonal cell lines, can impair the accuracy of pooled genetic screens.
  • The multi-level barcoding approach provides a robust method to identify and mitigate the effects of such heterogeneity.
  • This methodology enhances the reliability of CRISPR screening for systematic gene function investigation.