Testing the gene expression classification of the EMT spectrum

Jia, Dongya and George, Jason T and Tripathi, Satyendra C and Kundnani, Deepali L and Lu, Mingyang and Hanash, Samir M and Onuchic, Jose N and Jolly, Mohit Kumar and Levine, Herbert (2019) Testing the gene expression classification of the EMT spectrum. In: PHYSICAL BIOLOGY, 16 (2).

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Abstract

The epithelial-mesenchymal transition (EMT) plays a central role in cancer metastasis and drug resistance-two persistent clinical challenges. Epithelial cells can undergo a partial or full EMT, attaining either a hybrid epithelial/mesenchymal (E/M) or mesenchymal phenotype, respectively. Recent studies have emphasized that hybrid E/M cells may be more aggressive than their mesenchymal counterparts. However, mechanisms driving hybrid E/M phenotypes remain largely elusive. Here, to better characterize the hybrid E/M phenotype (s) and tumor aggressiveness, we integrate two computational methods-(a) RACIPE-to identify the robust gene expression patterns emerging from the dynamics of a given gene regulatory network, and (b) EMT scoring metric-to calculate the probability that a given gene expression profile displays a hybrid E/M phenotype. We apply the EMT scoring metric to RACIPE-generated gene expression data generated from a core EMT regulatory network and classify the gene expression profiles into relevant categories (epithelial, hybrid E/M, mesenchymal). This categorization is broadly consistent with hierarchical clustering readouts of RACIPE-generated gene expression data. We also show how the EMT scoring metric can be used to distinguish between samples composed of exclusively hybrid E/M cells and those containing mixtures of epithelial and mesenchymal subpopulations using the RACIPE-generated gene expression data.

Item Type:	Journal Article
Publication:	PHYSICAL BIOLOGY
Publisher:	IOP PUBLISHING LTD
Additional Information:	Copyright of this article belongs to IOP PUBLISHING LTD
Keywords:	epithelial-mesenchymal transition; EMT; random circuit perturbation; RACIPE; EMT scoringmetric; hybrid epithelial/mesenchymal; hybrid E/M
Department/Centre:	Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited:	12 Feb 2019 04:48
Last Modified:	12 Feb 2019 04:48
URI:	http://eprints.iisc.ac.in/id/eprint/61687

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