Systematic exploration of cell morphological phenotypes associated with a transcriptomic query

Nucleic Acids Research
Isar Nassiri, Matthew N McCall

Abstract

Cell morphological phenotypes, including shape, size, intensity, and texture of cellular compartments have been shown to change in response to perturbation with small molecule compounds. Image-based cell profiling or cell morphological profiling has been used to associate changes of cell morphological features with alterations in cellular function and to infer molecular mechanisms of action. Recently, the Library of Integrated Network-based Cellular Signatures (LINCS) Project has measured gene expression and performed image-based cell profiling on cell lines treated with 9515 unique compounds. These data provide an opportunity to study the interdependence between transcription and cell morphology. Previous methods to investigate cell phenotypes have focused on targeting candidate genes as components of known pathways, RNAi morphological profiling, and cataloging morphological defects; however, these methods do not provide an explicit model to link transcriptomic changes with corresponding alterations in morphology. To address this, we propose a cell morphology enrichment analysis to assess the association between transcriptomic alterations and changes in cell morphology. Additionally, for a new transcriptomic query, our approac...Continue Reading

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Citations

Feb 6, 2020·Molecular Biology of the Cell·Saradha VenkatachalapathyG V Shivashankar
Aug 5, 2020·Nature Communications·Benoît SchmauchGilles Wainrib
Feb 18, 2021·Trends in Biotechnology·Nathaniel F C HenningMonica M Laronda
Nov 5, 2020·Proceedings of the National Academy of Sciences of the United States of America·Rabih Darwiche, Kevin Struhl
Dec 24, 2020·Nature Reviews. Drug Discovery·Srinivas Niranj ChandrasekaranAnne E Carpenter

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Methods Mentioned

BETA
fluorescence imaging
RNA-seq

Software Mentioned

ZARDAVERINE
NOMILIN
CLR
CellProfiler
R
Funrich package
HYDROCOTARNINE
LASSO
CMEA ( Cell Morphology Enrichment Analysis )
qgraph

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