Drug-induced regulation of target expression.

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 differen...

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Autores principales:	Murat Iskar, Monica Campillos, Michael Kuhn, Lars Juhl Jensen, Vera van Noort, Peer Bork
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/72a3c901b8714a26a016442b9f7a0740
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spelling	oai:doaj.org-article:72a3c901b8714a26a016442b9f7a07402021-11-18T05:49:19ZDrug-induced regulation of target expression.1553-734X1553-735810.1371/journal.pcbi.1000925https://doaj.org/article/72a3c901b8714a26a016442b9f7a07402010-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20838579/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Drug 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.Murat IskarMurat IskarMonica CampillosMichael KuhnLars Juhl JensenVera van NoortPeer BorkPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 6, Iss 9 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Murat Iskar Murat Iskar Monica Campillos Michael Kuhn Lars Juhl Jensen Vera van Noort Peer Bork Drug-induced regulation of target expression.
description	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.
format	article
author	Murat Iskar Murat Iskar Monica Campillos Michael Kuhn Lars Juhl Jensen Vera van Noort Peer Bork
author_facet	Murat Iskar Murat Iskar Monica Campillos Michael Kuhn Lars Juhl Jensen Vera van Noort Peer Bork
author_sort	Murat Iskar
title	Drug-induced regulation of target expression.
title_short	Drug-induced regulation of target expression.
title_full	Drug-induced regulation of target expression.
title_fullStr	Drug-induced regulation of target expression.
title_full_unstemmed	Drug-induced regulation of target expression.
title_sort	drug-induced regulation of target expression.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/72a3c901b8714a26a016442b9f7a0740
work_keys_str_mv	AT muratiskar druginducedregulationoftargetexpression AT muratiskar druginducedregulationoftargetexpression AT monicacampillos druginducedregulationoftargetexpression AT michaelkuhn druginducedregulationoftargetexpression AT larsjuhljensen druginducedregulationoftargetexpression AT veravannoort druginducedregulationoftargetexpression AT peerbork druginducedregulationoftargetexpression
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Drug-induced regulation of target expression.

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