HLA3D

HLA3D integrates sequence, structural, population, and literature data to analyze human leukocyte antigen (HLA)/major histocompatibility complex (MHC) structural diversity and to predict antigenic peptides for immunotherapy and transplantation research.

Key Features:

• Extensive Data Integration: Consolidates 1,296 amino acid sequences, 256 Protein Data Bank (PDB) structures, 212 modelled HLA heterodimer structures, allele frequency information from 120,000 population samples, 73,000 related publications, and 39,000 disease-associated single nucleotide polymorphism (SNP) sites.
• Risk Alignment Pipeline: Leverages over 100,000 calculated HLA conformation differences and various online tools to perform structural and sequence alignment, residue visualization, and generation of mismatched HLA molecule risk reports.
• Antigenic Peptide Prediction Pipeline: Predicts 370,000 immunogenic peptides and compiles a neoantigen catalogue for 11 common tumors, supporting mutation prediction, peptide prediction, immunogenicity assessment, and docking simulation.
• Case Study Validation: Demonstrated prediction of antigenic peptides from hepatitis B virus mutations associated with liver cancer as an applied validation of the prediction pipeline.

Scientific Applications:

• Pathogenic mechanism investigation: Provides structural insights into HLA-linked disease mechanisms using integrated sequence, structure, SNP, and literature data.
• Transplantation risk assessment: Supports assessment of HLA mismatches and risk reporting for transplantation immunotherapy via structural and sequence alignment analyses.
• Cancer neoantigen discovery: Enables identification of tumor neoantigens and candidate immunogenic peptides for tumor immunotherapy across 11 common tumors.
• Precision medicine and targeted therapy design: Facilitates allele-specific association studies and the design of targeted immunotherapies informed by population allele frequencies and modeled HLA structures.

Methodology:

Integrates sequence and PDB structural data and modeled HLA heterodimers with allele frequency and SNP datasets; computes >100,000 HLA conformation differences; performs structural and sequence alignment, residue visualization, mismatched HLA risk report generation, mutation prediction, peptide affinity/immunogenicity prediction, and docking simulation within risk alignment and antigenic peptide prediction pipelines.