SpaRx: elucidate single-cell spatial heterogeneity of drug responses for personalized treatment.
Brief Bioinform
; 24(6)2023 09 22.
Article
em En
| MEDLINE
| ID: mdl-37798249
ABSTRACT
Spatial cellular authors heterogeneity contributes to differential drug responses in a tumor lesion and potential therapeutic resistance. Recent emerging spatial technologies such as CosMx, MERSCOPE and Xenium delineate the spatial gene expression patterns at the single cell resolution. This provides unprecedented opportunities to identify spatially localized cellular resistance and to optimize the treatment for individual patients. In this work, we present a graph-based domain adaptation model, SpaRx, to reveal the heterogeneity of spatial cellular response to drugs. SpaRx transfers the knowledge from pharmacogenomics profiles to single-cell spatial transcriptomics data, through hybrid learning with dynamic adversarial adaption. Comprehensive benchmarking demonstrates the superior and robust performance of SpaRx at different dropout rates, noise levels and transcriptomics coverage. Further application of SpaRx to the state-of-the-art single-cell spatial transcriptomics data reveals that tumor cells in different locations of a tumor lesion present heterogenous sensitivity or resistance to drugs. Moreover, resistant tumor cells interact with themselves or the surrounding constituents to form an ecosystem for drug resistance. Collectively, SpaRx characterizes the spatial therapeutic variability, unveils the molecular mechanisms underpinning drug resistance and identifies personalized drug targets and effective drug combinations.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ecossistema
/
Medicina de Precisão
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Brief Bioinform
Assunto da revista:
BIOLOGIA
/
INFORMATICA MEDICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos