AI identifies potent inducers of breast cancer stem cell differentiation based on adversarial learning from gene expression data.
Brief Bioinform
; 25(3)2024 Mar 27.
Article
en En
| MEDLINE
| ID: mdl-38701411
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Células Madre Neoplásicas
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Neoplasias de la Mama
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Diferenciación Celular
Límite:
Female
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Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article