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In vitro transcription studies used in a proof of concept whole transcriptome model predition study

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE109514 | GEO | 2018/12/21

REPOSITORIES: GEO

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In vitro transcription studies used in a proof of concept whole transcriptome model predition study

Project description:In vitro transcription studies used in a proof of concept whole transcriptome model predition study

| PRJNA431283 | ENA

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Project description:In vitro transcription studies used in a proof of concept whole transcriptome model predition study - A673 cells (1 of 4)

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Project description:In vitro transcription studies used in a proof of concept whole transcriptome model predition study - HepG2 cells (4 of 4)

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Molecular phenotyping empowers drug discovery: a proof-of-concept study

Project description:Today, novel candidate therapeutics are identified in an environment which is intrinsically different from the clinical context in which they are ultimately evaluated. We present a strategy that allows biological relevance to be assessed in the early stages of drug discovery. Using molecular phenotyping and an in vitro model of diabetic cardiomyopathy, we show that by quantifying pathway reporter gene expression, molecular phenotyping can cluster compounds based on pathway profiles and dissect associations between pathway activities and disease phenotypes simultaneously. Molecular phenotyping identified a class of calcium-signaling modulators that can reverse disease-regulated pathways and phenotypes, which was validated by structurally distinct compounds of relevant classes. The technique was applicable to compounds with a range of binding specificities and detected false-positive hits missed by classical phenotypic assays. Our results advocate application of molecular phenotyping in drug discovery, promoting biological relevance as a key selection criterion early in the drug development cascade.

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