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Elife DOI:10.7554/eLife.24060

Systematic morphological profiling of human gene and allele function via Cell Painting.

Publication TypeJournal Article
Year of Publication2017
AuthorsRohban, MHossein, Singh, S, Wu, X, Berthet, JB, Bray, M-A, Shrestha, Y, Varelas, X, Boehm, JS, Carpenter, AE
JournalElife
Volume6
Date Published2017 Mar 18
ISSN2050-084X
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.

DOI10.7554/eLife.24060
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/28315521?dopt=Abstract

Alternate JournalElife
PubMed ID28315521
PubMed Central IDPMC5386591