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...
| Үндсэн зохиолчид: | , , , , , |
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| Формат: | Өгүүллэг |
| Хэл сонгох: | English |
| Хэвлэсэн: |
Public Library of Science (PLoS)
2010-09-01
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| Цуврал: | PLoS Computational Biology |
| Онлайн хандалт: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20838579/pdf/?tool=EBI |
| Тойм: | 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. |
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| ISSN: | 1553-734X 1553-7358 |