RESUMO
Human leukocyte antigen (HLA) molecules play critically significant role within the realm of immunotherapy due to their capacities to recognize and bind exogenous antigens such as peptides, subsequently delivering them to immune cells. Predicting the binding between peptides and HLA molecules (pHLA) can expedite the screening of immunogenic peptides and facilitate vaccine design. However, traditional experimental methods are time-consuming and inefficient. In this study, an efficient method based on deep learning was developed for predicting peptide-HLA binding, which treated peptide sequences as linguistic entities. It combined the architectures of textCNN and BiLSTM to create a deep neural network model called APEX-pHLA. This model operated without limitations related to HLA class I allele variants and peptide segment lengths, enabling efficient encoding of sequence features for both HLA and peptide segments. On the independent test set, the model achieved Accuracy, ROC_AUC, F1, and MCC is 0.9449, 0.9850, 0.9453, and 0.8899, respectively. Similarly, on an external test set, the results were 0.9803, 0.9574, 0.8835, and 0.7863, respectively. These findings outperformed fifteen methods previously reported in the literature. The accurate prediction capability of the APEX-pHLA model in peptide-HLA binding might provide valuable insights for future HLA vaccine design.
Assuntos
Antígenos de Histocompatibilidade Classe I , Peptídeos , Ligação Proteica , Humanos , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Peptídeos/química , Peptídeos/imunologia , Aprendizado Profundo , Antígenos HLA/imunologia , Antígenos HLA/genética , Redes Neurais de Computação , Biologia Computacional/métodosRESUMO
A seroepidemiological study was conducted in 2018 to assess diphtheria and tetanus antibodies in Guangzhou, China. Diphtheria and tetanus antibody concentrations were measured with an enzyme-linked immunosorbent assay. A total of 715 subjects were enrolled in the study. The overall diphtheria and tetanus toxoid IgG-specific antibody levels were 0.126 IU/mL (95% CI: 0.115, 0.137) and 0.210 IU/mL (95% CI: 0.185, 0.240), respectively; the overall positivity rate was 61.82% (95% CI: 58.14, 65.39) and 71.61% (95% CI: 68.3, 74.92), respectively. The diphtheria and tetanus antibody concentration was decreased by age and increased by doses. The geometric mean concentrations and positivity rate of diphtheria and tetanus antibodies were lowest and below the essential protection level in people over 14 years of age. Compared to children and adolescents, middle-aged people and the aged are at much higher risk of infection with Corynebacterium diphtheriae and Clostridium tetani. The current diphtheria and tetanus immunization schedule does not provide persistent protection after childhood. There is an urgent need to adjust the current immunization schedule.
RESUMO
Cyclic peptides are gaining attention for their strong binding affinity, low toxicity, and ability to target "undruggable" proteins; however, their therapeutic potential against intracellular targets is constrained by their limited membrane permeability, and researchers need much time and money to test this property in the laboratory. Herein, we propose an innovative multimodal model called Multi_CycGT, which combines a graph convolutional network (GCN) and a transformer to extract one- and two-dimensional features for predicting cyclic peptide permeability. The extensive benchmarking experiments show that our Multi_CycGT model can attain state-of-the-art performance, with an average accuracy of 0.8206 and an area under the curve of 0.8650, and demonstrates satisfactory generalization ability on several external data sets. To the best of our knowledge, it is the first deep learning-based attempt to predict the membrane permeability of cyclic peptides, which is beneficial in accelerating the design of cyclic peptide active drugs in medicinal chemistry and chemical biology applications.