Drug-induced regulation of target expression

Research output: Contribution to journalJournal articlepeer-review

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Drug-induced regulation of target expression. / Iskar, Murat; Campillos, Monica; Kuhn, Michael; Jensen, Lars Juhl; van Noort, Vera; Bork, Peer.

In: PLoS Computational Biology, Vol. 6, No. 9, 01.01.2010.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Iskar, M, Campillos, M, Kuhn, M, Jensen, LJ, van Noort, V & Bork, P 2010, 'Drug-induced regulation of target expression', PLoS Computational Biology, vol. 6, no. 9. https://doi.org/10.1371/journal.pcbi.1000925

APA

Iskar, M., Campillos, M., Kuhn, M., Jensen, L. J., van Noort, V., & Bork, P. (2010). Drug-induced regulation of target expression. PLoS Computational Biology, 6(9). https://doi.org/10.1371/journal.pcbi.1000925

Vancouver

Iskar M, Campillos M, Kuhn M, Jensen LJ, van Noort V, Bork P. Drug-induced regulation of target expression. PLoS Computational Biology. 2010 Jan 1;6(9). https://doi.org/10.1371/journal.pcbi.1000925

Author

Iskar, Murat ; Campillos, Monica ; Kuhn, Michael ; Jensen, Lars Juhl ; van Noort, Vera ; Bork, Peer. / Drug-induced regulation of target expression. In: PLoS Computational Biology. 2010 ; Vol. 6, No. 9.

Bibtex

@article{32a1e606428347418b3b384ab36fa0ef,
title = "Drug-induced regulation of target expression",
abstract = "Drug perturbations of human cells lead to complex responses upon target binding. One of the known mechanisms is a (positive or negative) feedback loop that adjusts the expression level of the respective target protein. To quantify this mechanism systems-wide in an unbiased way, drug-induced differential expression of drug target mRNA was examined in three cell lines using the Connectivity Map. To overcome various biases in this valuable resource, we have developed a computational normalization and scoring procedure that is applicable to gene expression recording upon heterogeneous drug treatments. In 1290 drug-target relations, corresponding to 466 drugs acting on 167 drug targets studied, 8% of the targets are subject to regulation at the mRNA level. We confirmed systematically that in particular G-protein coupled receptors, when serving as known targets, are regulated upon drug treatment. We further newly identified drug-induced differential regulation of Lanosterol 14-alpha demethylase, Endoplasmin, DNA topoisomerase 2-alpha and Calmodulin 1. The feedback regulation in these and other targets is likely to be relevant for the success or failure of the molecular intervention.",
keywords = "Cell Line, Tumor, Databases, Genetic, Drug Discovery, Feedback, Physiological, Gene Expression Profiling, Genomics, HL-60 Cells, Humans, Molecular Targeted Therapy, Oligonucleotide Array Sequence Analysis, Pharmaceutical Preparations, Pharmacological Processes, Proteins, RNA, Messenger, Receptors, G-Protein-Coupled, Statistics, Nonparametric, Systems Biology",
author = "Murat Iskar and Monica Campillos and Michael Kuhn and Jensen, {Lars Juhl} and {van Noort}, Vera and Peer Bork",
year = "2010",
month = jan,
day = "1",
doi = "10.1371/journal.pcbi.1000925",
language = "English",
volume = "6",
journal = "P L o S Computational Biology (Online)",
issn = "1553-734X",
publisher = "Public Library of Science",
number = "9",

}

RIS

TY - JOUR

T1 - Drug-induced regulation of target expression

AU - Iskar, Murat

AU - Campillos, Monica

AU - Kuhn, Michael

AU - Jensen, Lars Juhl

AU - van Noort, Vera

AU - Bork, Peer

PY - 2010/1/1

Y1 - 2010/1/1

N2 - Drug perturbations of human cells lead to complex responses upon target binding. One of the known mechanisms is a (positive or negative) feedback loop that adjusts the expression level of the respective target protein. To quantify this mechanism systems-wide in an unbiased way, drug-induced differential expression of drug target mRNA was examined in three cell lines using the Connectivity Map. To overcome various biases in this valuable resource, we have developed a computational normalization and scoring procedure that is applicable to gene expression recording upon heterogeneous drug treatments. In 1290 drug-target relations, corresponding to 466 drugs acting on 167 drug targets studied, 8% of the targets are subject to regulation at the mRNA level. We confirmed systematically that in particular G-protein coupled receptors, when serving as known targets, are regulated upon drug treatment. We further newly identified drug-induced differential regulation of Lanosterol 14-alpha demethylase, Endoplasmin, DNA topoisomerase 2-alpha and Calmodulin 1. The feedback regulation in these and other targets is likely to be relevant for the success or failure of the molecular intervention.

AB - Drug perturbations of human cells lead to complex responses upon target binding. One of the known mechanisms is a (positive or negative) feedback loop that adjusts the expression level of the respective target protein. To quantify this mechanism systems-wide in an unbiased way, drug-induced differential expression of drug target mRNA was examined in three cell lines using the Connectivity Map. To overcome various biases in this valuable resource, we have developed a computational normalization and scoring procedure that is applicable to gene expression recording upon heterogeneous drug treatments. In 1290 drug-target relations, corresponding to 466 drugs acting on 167 drug targets studied, 8% of the targets are subject to regulation at the mRNA level. We confirmed systematically that in particular G-protein coupled receptors, when serving as known targets, are regulated upon drug treatment. We further newly identified drug-induced differential regulation of Lanosterol 14-alpha demethylase, Endoplasmin, DNA topoisomerase 2-alpha and Calmodulin 1. The feedback regulation in these and other targets is likely to be relevant for the success or failure of the molecular intervention.

KW - Cell Line, Tumor

KW - Databases, Genetic

KW - Drug Discovery

KW - Feedback, Physiological

KW - Gene Expression Profiling

KW - Genomics

KW - HL-60 Cells

KW - Humans

KW - Molecular Targeted Therapy

KW - Oligonucleotide Array Sequence Analysis

KW - Pharmaceutical Preparations

KW - Pharmacological Processes

KW - Proteins

KW - RNA, Messenger

KW - Receptors, G-Protein-Coupled

KW - Statistics, Nonparametric

KW - Systems Biology

U2 - 10.1371/journal.pcbi.1000925

DO - 10.1371/journal.pcbi.1000925

M3 - Journal article

C2 - 20838579

VL - 6

JO - P L o S Computational Biology (Online)

JF - P L o S Computational Biology (Online)

SN - 1553-734X

IS - 9

ER -

ID: 33748459