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...
| Main Authors: | , , , , , |
|---|---|
| 格式: | 文件 |
| 语言: | English |
| 出版: |
Public Library of Science (PLoS)
2010-09-01
|
| 丛编: | PLoS Computational Biology |
| 在线阅读: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20838579/pdf/?tool=EBI |
| _version_ | 1828747979213766656 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-14T04:53:00Z |
| format | Article |
| id | doaj.art-72a3c901b8714a26a016442b9f7a0740 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-04-14T04:53:00Z |
| publishDate | 2010-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-72a3c901b8714a26a016442b9f7a07402022-12-22T02:11:13ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582010-09-0169e100092510.1371/journal.pcbi.1000925Drug-induced regulation of target expression. Murat IskarMurat IskarMonica CampillosMichael KuhnLars Juhl JensenVera van NoortPeer BorkDrug 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20838579/pdf/?tool=EBI |
| spellingShingle | Murat Iskar Murat Iskar Monica Campillos Michael Kuhn Lars Juhl Jensen Vera van Noort Peer Bork Drug-induced regulation of target expression. PLoS Computational Biology |
| title | 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_short | Drug-induced regulation of target expression. |
| title_sort | drug induced regulation of target expression |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20838579/pdf/?tool=EBI |
| 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 |