PMID- 35289353 OWN - NLM STAT- MEDLINE DCOM- 20220523 LR - 20220611 IS - 1477-4054 (Electronic) IS - 1467-5463 (Print) IS - 1467-5463 (Linking) VI - 23 IP - 3 DP - 2022 May 13 TI - HLA3D: an integrated structure-based computational toolkit for immunotherapy. LID - 10.1093/bib/bbac076 [doi] LID - bbac076 AB - 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/. CI - (c) The Author(s) 2022. Published by Oxford University Press. FAU - Li, Xingyu AU - Li X AD - Key Laboratory of DGHD, MOE, School of Life Science and Technology, Southeast University, Nanjing, China. FAU - Lin, Xue AU - Lin X AD - Department of Bioinformatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China. FAU - Mei, Xueyin AU - Mei X AD - Key Laboratory of DGHD, MOE, School of Life Science and Technology, Southeast University, Nanjing, China. FAU - Chen, Pin AU - Chen P AD - Key Laboratory of DGHD, MOE, School of Life Science and Technology, Southeast University, Nanjing, China. FAU - Liu, Anna AU - Liu A AD - Key Laboratory of DGHD, MOE, School of Life Science and Technology, Southeast University, Nanjing, China. FAU - Liang, Weicheng AU - Liang W AUID- ORCID: 0000-0002-8708-1143 AD - Key Laboratory of DGHD, MOE, School of Life Science and Technology, Southeast University, Nanjing, China. FAU - Chang, Shan AU - Chang S AUID- ORCID: 0000-0001-7169-9398 AD - Institute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou, China. FAU - Li, Jian AU - Li J AUID- ORCID: 0000-0001-8706-6421 AD - Key Laboratory of DGHD, MOE, School of Life Science and Technology, Southeast University, Nanjing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Brief Bioinform JT - Briefings in bioinformatics JID - 100912837 RN - 0 (HLA Antigens) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Peptides) SB - IM MH - Computational Biology MH - HLA Antigens/genetics MH - *Histocompatibility Antigens Class I/chemistry MH - Humans MH - Immunotherapy MH - *Neoplasms MH - Peptides/chemistry MH - Protein Binding PMC - PMC9116210 OTO - NOTNLM OT - HLA structure OT - mutation OT - neoantigen prediction OT - organ transplantation EDAT- 2022/03/16 06:00 MHDA- 2022/05/24 06:00 PMCR- 2022/03/14 CRDT- 2022/03/15 08:43 PHST- 2021/12/20 00:00 [received] PHST- 2022/02/12 00:00 [revised] PHST- 2022/02/14 00:00 [accepted] PHST- 2022/03/16 06:00 [pubmed] PHST- 2022/05/24 06:00 [medline] PHST- 2022/03/15 08:43 [entrez] PHST- 2022/03/14 00:00 [pmc-release] AID - 6548371 [pii] AID - bbac076 [pii] AID - 10.1093/bib/bbac076 [doi] PST - ppublish SO - Brief Bioinform. 2022 May 13;23(3):bbac076. doi: 10.1093/bib/bbac076.