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HLA3D: an integrated structure-based computational toolkit for immunotherapy.
Li, Xingyu; Lin, Xue; Mei, Xueyin; Chen, Pin; Liu, Anna; Liang, Weicheng; Chang, Shan; Li, Jian.
  • Li X; Key Laboratory of DGHD, MOE, School of Life Science and Technology, Southeast University, Nanjing, China.
  • Lin X; Department of Bioinformatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China.
  • Mei X; Key Laboratory of DGHD, MOE, School of Life Science and Technology, Southeast University, Nanjing, China.
  • Chen P; Key Laboratory of DGHD, MOE, School of Life Science and Technology, Southeast University, Nanjing, China.
  • Liu A; Key Laboratory of DGHD, MOE, School of Life Science and Technology, Southeast University, Nanjing, China.
  • Liang W; Key Laboratory of DGHD, MOE, School of Life Science and Technology, Southeast University, Nanjing, China.
  • Chang S; Institute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou, China.
  • Li J; Key Laboratory of DGHD, MOE, School of Life Science and Technology, Southeast University, Nanjing, China.
Brief Bioinform ; 23(3)2022 05 13.
Article en En | MEDLINE | ID: mdl-35289353
ABSTRACT
MOTIVATION The human major histocompatibility complex (MHC), also known as human leukocyte antigen (HLA), plays an important role in the adaptive immune system by presenting non-self-peptides to T cell receptors. The MHC region has been shown to be associated with a variety of diseases, including autoimmune diseases, organ transplantation and tumours. However, structural analytic tools of HLA are still sparse compared to the number of identified HLA alleles, which hinders the disclosure of its pathogenic mechanism.

RESULT:

To provide an integrative analysis of HLA, we first collected 1296 amino acid sequences, 256 protein data bank structures, 120 000 frequency data of HLA alleles in different populations, 73 000 publications and 39 000 disease-associated single nucleotide polymorphism sites, as well as 212 modelled HLA heterodimer structures. Then, we put forward two new strategies for building up a toolkit for transplantation and tumour immunotherapy, designing risk alignment pipeline and antigenic peptide prediction pipeline by integrating different resources and bioinformatic tools. By integrating 100 000 calculated HLA conformation difference and online tools, risk alignment pipeline provides users with the functions of structural alignment, sequence alignment, residue visualization and risk report generation of mismatched HLA molecules. For tumour antigen prediction, we first predicted 370 000 immunogenic peptides based on the affinity between peptides and MHC to generate the neoantigen catalogue for 11 common tumours. We then designed an antigenic peptide prediction pipeline to provide the functions of mutation prediction, peptide prediction, immunogenicity assessment and docking simulation. We also present a case study of hepatitis B virus mutations associated with liver cancer that demonstrates the high legitimacy of our antigenic peptide prediction process. HLA3D, including different HLA analytic tools and the prediction pipelines, is available at http//www.hla3d.cn/.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Antígenos de Histocompatibilidad Clase I / Neoplasias Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Año: 2022 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Antígenos de Histocompatibilidad Clase I / Neoplasias Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Año: 2022 Tipo del documento: Article