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AI identifies potent inducers of breast cancer stem cell differentiation based on adversarial learning from gene expression data.
- Source :
- Briefings in Bioinformatics; May2024, Vol. 25 Issue 3, p1-14, 14p
- Publication Year :
- 2024
-
Abstract
- Cancer stem cells (CSCs) are a subpopulation of cancer cells within tumors that exhibit stem-like properties and represent a potentially effective therapeutic target toward long-term remission by means of differentiation induction. By leveraging an artificial intelligence approach solely based on transcriptomics data, this study scored a large library of small molecules based on their predicted ability to induce differentiation in stem-like cells. In particular, a deep neural network model was trained using publicly available single-cell RNA-Seq data obtained from untreated human-induced pluripotent stem cells at various differentiation stages and subsequently utilized to screen drug-induced gene expression profiles from the Library of Integrated Network-based Cellular Signatures (LINCS) database. The challenge of adapting such different data domains was tackled by devising an adversarial learning approach that was able to effectively identify and remove domain-specific bias during the training phase. Experimental validation in MDA-MB-231 and MCF7 cells demonstrated the efficacy of five out of six tested molecules among those scored highest by the model. In particular, the efficacy of triptolide, OTS-167, quinacrine, granisetron and A-443654 offer a potential avenue for targeted therapies against breast CSCs. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14675463
- Volume :
- 25
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Briefings in Bioinformatics
- Publication Type :
- Academic Journal
- Accession number :
- 177375832
- Full Text :
- https://doi.org/10.1093/bib/bbae207