ArticleMolecular systems biology2016
Parallel reverse genetic screening in mutant human cells using transcriptomics.
Article in Molecular systems biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Detecting subtle transcriptomic perturbations induced by lncRNAs knock-down in single-cell CRISPRi screening using a new sparse supervised autoencoder neural network.Frontiers in bioinformatics · 2024Article
- Application of modular response analysis to medium- to large-size biological systems.PLoS computational biology · 2022Article
- STAT1 gain-of-function heterozygous cell models reveal diverse interferon-signature gene transcriptional responses.NPJ genomic medicine · 2021Article
- Integrative analysis of microRNA and mRNA expression profiles of monocyte-derived dendritic cells differentiation during experimental cerebral malaria.Journal of leukocyte biology · 2020Article
- Incremental data integration for tracking genotype-disease associations.PLoS computational biology · 2020Article
- Discovery of a Highly Selective Cell-Active Inhibitor of the Histone Lysine Demethylases KDM2/7.Angewandte Chemie (International ed. in English) · 2017Article
- A small cassette enables conditional gene inactivation by CRISPR/Cas9.Scientific reports · 2017Article
- Pooled CRISPR screening with single-cell transcriptome readout.Nature methods · 2017Article
- Parallel reverse genetic screening in mutant human cells using transcriptomics.Molecular systems biology · 2016Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Reverse genetic screens have driven gene annotation and target discovery in model organisms. However, many disease-relevant genotypes and phenotypes cannot be studied in lower organisms. It is therefore essential to overcome technical hurdles associated with large-scale reverse genetics in human cells. Here, we establish a reverse genetic approach based on highly robust and sensitive multiplexed RNA sequencing of mutant human cells. We conduct 10 parallel screens using a collection of engineered haploid isogenic cell lines with knockouts covering tyrosine kinases and identify known and unexpected effects on signaling pathways. Our study provides proof of concept for a scalable approach to link genotype to phenotype in human cells, which has broad applications. In particular, it clears the way for systematic phenotyping of still poorly characterized human genes and for systematic study of uncharacterized genomic features associated with human disease.
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