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Interpretable Prediction of SARS-CoV-2 Epitope-Specific TCR Recognition Using a Pre-Trained Protein Language Model.
Article en En | MEDLINE | ID: mdl-38381638
ABSTRACT
The emergence of the novel coronavirus, designated as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has posed a significant threat to public health worldwide. There has been progress in reducing hospitalizations and deaths due to SARS-CoV-2. However, challenges stem from the emergence of SARS-CoV-2 variants, which exhibit high transmission rates, increased disease severity, and the ability to evade humoral immunity. Epitope-specific T-cell receptor (TCR) recognition is key in determining the T-cell immunogenicity for SARS-CoV-2 epitopes. Although several data-driven methods for predicting epitope-specific TCR recognition have been proposed, they remain challenging due to the enormous diversity of TCRs and the lack of available training data. Self-supervised transfer learning has recently been proven useful for extracting information from unlabeled protein sequences, increasing the predictive performance of fine-tuned models, and using a relatively small amount of training data. This study presents a deep-learning model generated by fine-tuning pre-trained protein embeddings from a large corpus of protein sequences. The fine-tuned model showed markedly high predictive performance and outperformed the recent Gaussian process-based prediction model. The output attentions captured by the deep-learning model suggested critical amino acid positions in the SARS-CoV-2 epitope-specific TCRß sequences that are highly associated with the viral escape of T-cell immune response.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Antígenos de Linfocitos T / Epítopos de Linfocito T / Biología Computacional / SARS-CoV-2 / COVID-19 Límite: Humans Idioma: En Revista: ACM Trans Comput Biol Bioinform Asunto de la revista: BIOLOGIA / INFORMATICA MEDICA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Antígenos de Linfocitos T / Epítopos de Linfocito T / Biología Computacional / SARS-CoV-2 / COVID-19 Límite: Humans Idioma: En Revista: ACM Trans Comput Biol Bioinform Asunto de la revista: BIOLOGIA / INFORMATICA MEDICA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos