ArticlePLoS computational biology2010
Drug-induced regulation of target expression.
Article in PLoS computational biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed.
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- Compartment Model and Neural Network-Based Analysis of Combination Medication Ratios.Pharmaceutics · 2025Article
- Increased expression of ER stress, inflammasome activation, and mitochondrial biogenesis-related genes in peripheral blood mononuclear cells in major depressive disorder.Molecular psychiatry · 2025Article
- SNHG4-mediated PTEN destabilization confers oxaliplatin resistance in colorectal cancer cells by inhibiting ferroptosis.Apoptosis : an international journal on programmed cell death · 2024Article
- Optimizing in silico drug discovery: simulation of connected differential expression signatures and applications to benchmarking.Briefings in bioinformatics · 2024Article
- Graph-DTI: A New Model for Drug-target Interaction Prediction Based on Heterogenous Network Graph Embedding.Current computer-aided drug design · 2024Article
- Cell-based screen identifies porphyrins as FGFR3 activity inhibitors with therapeutic potential for achondroplasia and cancer.JCI insight · 2023Article
- DOSE-L1000: unveiling the intricate landscape of compound-induced transcriptional changes.Bioinformatics (Oxford, England) · 2023Article
- A proteome-wide atlas of drug mechanism of action.Nature biotechnology · 2023Article
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- Navigating Transcriptomic Connectivity Mapping Workflows to Link Chemicals with Bioactivities.Chemical research in toxicology · 2022Review
- Regulome-based characterization of drug activity across the human diseasome.NPJ systems biology and applications · 2022Article
- Integrating and formatting biomedical data as pre-calculated knowledge graph embeddings in the Bioteque.Nature communications · 2022Article
- Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response.Pharmaceuticals (Basel, Switzerland) · 2022Review
- A Potential Indicator ARRDC2 Has Feasibility to Evaluate Prognosis and Immune Microenvironment in Ovarian Cancer.Frontiers in genetics · 2022Article
- Development of a chemogenomics library for phenotypic screening.Journal of cheminformatics · 2021Article
- Reconciling multiple connectivity scores for drug repurposing.Briefings in bioinformatics · 2021Article
- Modeling drug mechanism of action with large scale gene-expression profiles using GPAR, an artificial intelligence platform.BMC bioinformatics · 2021Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.