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Tumor-associated antigen prediction using a single-sample gene expression state inference algorithm.

Xinpei Yi1, Hongwei Zhao2, Shunjie Hu2

  • 1Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.

Cell Reports Methods
|November 19, 2024
PubMed
Summary
This summary is machine-generated.

Researchers identified 212 tumor-associated antigens (TAAs) using a novel algorithm and RNA sequencing data. Eighteen TAAs were validated, with 10 showing promise for liver cancer immunotherapy, including specific peptides with strong HLA binding.

Keywords:
Bayesian algorithmCAR-TCP: Cancer biologyCP: Systems biologyCPTACTCGAgene expression state inferenceimmunotherapyliver cancerpan-cancertherapeutic targettumor-associated antigen

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Area of Science:

  • Genomics
  • Immunology
  • Bioinformatics

Background:

  • Tumor-associated antigens (TAAs) are crucial targets for cancer immunotherapy.
  • Identifying novel TAAs requires robust computational and experimental validation methods.

Purpose of the Study:

  • To develop and apply a Bayesian-based algorithm for identifying TAAs across diverse cancer types.
  • To validate candidate TAAs using independent datasets and experimental methods.
  • To discover potential therapeutic targets for liver cancer immunotherapy.

Main Methods:

  • Bayesian-based algorithm for gene expression state inference.
  • Analysis of RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) projects.
  • Validation using independent RNA-seq datasets, proteomics data, and experimental assays for peptide binding and immunogenicity.

Main Results:

  • Identified 212 candidate TAAs across 33 cancer types.
  • Validated 78 TAAs in independent datasets and 18 TAAs with proteomics data.
  • Discovered 10 TAAs linked to liver cancer, with 21 predicted peptides showing strong HLA-A02 binding and immunogenicity.
  • Found that ~64% of liver tumors express TAAs associated with these validated peptides.

Conclusions:

  • The integrated computational and experimental approach successfully identified and validated promising TAAs for cancer immunotherapy.
  • The discovered TAAs and peptides represent potential therapeutic candidates for liver cancer, including peptide vaccines and T cell receptor (TCR)-T cell therapies.
  • This study underscores the value of multi-omics data integration for advancing precision oncology.