Modeling drug mechanism of action with large scale gene-expression profiles using GPAR, an artificial intelligence platform
Open Access
- 7 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in BMC Bioinformatics
- Vol. 22 (1), 1-13
- https://doi.org/10.1186/s12859-020-03915-6
Abstract
Querying drug-induced gene expression profiles with machine learning method is an effective way for revealing drug mechanism of actions (MOAs), which is strongly supported by the growth of large scale and high-throughput gene expression databases. However, due to the lack of code-free and user friendly applications, it is not easy for biologists and pharmacologists to model MOAs with state-of-art deep learning approach. In this work, a newly developed online collaborative tool, Genetic profile-activity relationship (GPAR) was built to help modeling and predicting MOAs easily via deep learning. The users can use GPAR to customize their training sets to train self-defined MOA prediction models, to evaluate the model performances and to make further predictions automatically. Cross-validation tests show GPAR outperforms Gene set enrichment analysis in predicting MOAs. GPAR can serve as a better approach in MOAs prediction, which may facilitate researchers to generate more reliable MOA hypothesis.Keywords
Funding Information
- This work is supported by National Natural Science Foundation of China (81803431)
This publication has 42 references indexed in Scilit:
- Piperlongumine inhibits NF‐κB activity and attenuates aggressive growth characteristics of prostate cancer cellsThe Prostate, 2013
- GeneExpressionSignature: an R package for discovering functional connections using gene expression signaturesOMICS: A Journal of Integrative Biology, 2013
- DvD: An R/Cytoscape pipeline for drug repurposing using public repositories of gene expression dataBioinformatics, 2012
- The sva package for removing batch effects and other unwanted variation in high-throughput experimentsBioinformatics, 2012
- Drug-Induced Regulation of Target ExpressionPLoS Computational Biology, 2010
- The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes, and DiseaseScience, 2006
- NF‐kB inhibition as a strategy to enhance etoposide‐induced apoptosis in K562 cell lineAmerican Journal of Hematology, 2006
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005
- Suppression of IL-8 gene expression by radicicol is mediated through the inhibition of ERK1/2 and p38 signaling and negative regulation of NF-κB and AP-1International Immunopharmacology, 2001
- Competitive antagonism of serotonin (5-HT)2C and 5-HT2A receptormediated phosphoinositide (PI) turnover by clozapine in the rat: A comparison to other antipsychoticsNeuroscience Letters, 1994