Contextual AI models for single-cell protein biology.
Nat Methods
; 21(8): 1546-1557, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-39039335
ABSTRACT
Understanding protein function and developing molecular therapies require deciphering the cell types in which proteins act as well as the interactions between proteins. However, modeling protein interactions across biological contexts remains challenging for existing algorithms. Here we introduce PINNACLE, a geometric deep learning approach that generates context-aware protein representations. Leveraging a multiorgan single-cell atlas, PINNACLE learns on contextualized protein interaction networks to produce 394,760 protein representations from 156 cell type contexts across 24 tissues. PINNACLE's embedding space reflects cellular and tissue organization, enabling zero-shot retrieval of the tissue hierarchy. Pretrained protein representations can be adapted for downstream tasks enhancing 3D structure-based representations for resolving immuno-oncological protein interactions, and investigating drugs' effects across cell types. PINNACLE outperforms state-of-the-art models in nominating therapeutic targets for rheumatoid arthritis and inflammatory bowel diseases and pinpoints cell type contexts with higher predictive capability than context-free models. PINNACLE's ability to adjust its outputs on the basis of the context in which it operates paves the way for large-scale context-specific predictions in biology.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Análise de Célula Única
/
Aprendizado Profundo
Limite:
Humans
Idioma:
En
Revista:
Nat Methods
Ano de publicação:
2024
Tipo de documento:
Article