Systematic morphological profiling of human gene and allele function via Cell Painting
- Broad Institute, United States
- Boston University School of Medicine, United States
- Novartis Institutes for BioMedical Research, United States
Abstract
We hypothesized that human genes and disease-associated alleles might be systematically functionally annotated using morphological profiling of cDNA constructs, via a microscopy-based Cell Painting assay. Indeed, 50% of the 220 tested genes yielded detectable morphological profiles, which grouped into biologically meaningful gene clusters consistent with known functional annotation (e.g., the RAS-RAF-MEK-ERK cascade). We used novel subpopulation-based visualization methods to interpret the morphological changes for specific clusters. This unbiased morphologic map of gene function revealed TRAF2/c-REL negative regulation of YAP1/WWTR1-responsive pathways. We confirmed this discovery of functional connectivity between the NF-κB pathway and Hippo pathway effectors at the transcriptional level, thereby expanding knowledge of these two signaling pathways that critically regulate tumor initiation and progression. We make the images and raw data publicly available, providing an initial morphological map of major biological pathways for future study.
Data availability
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Target Accelerator OEPublicly available at the Image Data Resource (http://idr-demo.openmicroscopy.org/about/).
Article and author information
Author details
Mohammad Hossein Rohban
Funding
National Science Foundation (NSF CAREER DBI 1148823)
- Anne E Carpenter
Broad Institute
- Anne E Carpenter
Carlos Slim Foundation
- Anne E Carpenter
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jeffrey Settleman, Calico Life Sciences, United States
Version history
- Received: December 7, 2016
- Accepted: March 14, 2017
- Accepted Manuscript published: March 18, 2017 (version 1)
- Version of Record published: April 10, 2017 (version 2)
Copyright
© 2017, Rohban et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Systematic morphological profiling of human gene and allele function via Cell Painting
eLife 6:e24060.
https://doi.org/10.7554/eLife.24060
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