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A network-based phenotype mapping approach to identify genes that modulate drug response phenotypes.


ABSTRACT: To better address the problem of drug resistance during cancer chemotherapy and explore the possibility of manipulating drug response phenotypes, we developed a network-based phenotype mapping approach (P-Map) to identify gene candidates that upon perturbed can alter sensitivity to drugs. We used basal transcriptomics data from a panel of human lymphoblastoid cell lines (LCL) to infer drug response networks (DRNs) that are responsible for conferring response phenotypes for anthracycline and taxane, two common anticancer agents use in clinics. We further tested selected gene candidates that interact with phenotypic differentially expressed genes (PDEGs), which are up-regulated genes in LCL for a given class of drug response phenotype in triple-negative breast cancer (TNBC) cells. Our results indicate that it is possible to manipulate a drug response phenotype, from resistant to sensitive or vice versa, by perturbing gene candidates in DRNs and suggest plausible mechanisms regulating directionality of drug response sensitivity. More important, the current work highlights a new way to formulate systems-based therapeutic design: supplementing therapeutics that aim to target disease culprits with phenotypic modulators capable of altering DRN properties with the goal to re-sensitize resistant phenotypes.

SUBMITTER: Cairns J 

PROVIDER: S-EPMC5107984 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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A network-based phenotype mapping approach to identify genes that modulate drug response phenotypes.

Cairns Junmei J   Ung Choong Yong CY   da Rocha Edroaldo Lummertz EL   Zhang Cheng C   Correia Cristina C   Weinshilboum Richard R   Wang Liewei L   Li Hu H  

Scientific reports 20161114


To better address the problem of drug resistance during cancer chemotherapy and explore the possibility of manipulating drug response phenotypes, we developed a network-based phenotype mapping approach (P-Map) to identify gene candidates that upon perturbed can alter sensitivity to drugs. We used basal transcriptomics data from a panel of human lymphoblastoid cell lines (LCL) to infer drug response networks (DRNs) that are responsible for conferring response phenotypes for anthracycline and taxa  ...[more]

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