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

Elife
Authors
Keywords
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.

Year of Publication
2017
Journal
Elife
Volume
6
Date Published
2017 03 18
ISSN
2050-084X
DOI
10.7554/eLife.24060
PubMed ID
28315521
PubMed Central ID
PMC5386591
Links
Grant list
F31 HL132506 / HL / NHLBI NIH HHS / United States
T32 HL007035 / HL / NHLBI NIH HHS / United States