ASNEO: Identification of personalized alternative splicing based neoantigens with RNA-seq

Zhanbing Zhang1, Chi Zhou1, Lihua Tang2

  • 1Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital; Bioinformatics Department, School of Life Sciences and Technology, Tongji University, Shanghai 200009, China.

Aging
|July 23, 2020
PubMed

Insights

This study introduces ASNEO, a tool identifying cancer neoantigens from alternative splicing events using RNA-seq. These novel neoantigens show higher immune scores and can predict patient survival, advancing personalized cancer vaccines.

Area of Science:

  • Oncology
  • Immunology
  • Bioinformatics

Background:

  • Cancer neoantigens are crucial for immunotherapy.
  • Current methods primarily identify neoantigens from SNVs, indels, or gene fusions.
  • Alternative splicing is prevalent in tumors and generates neoantigens.

Purpose of the Study:

  • To present ASNEO, a computational pipeline for identifying personalized alternative splicing-based neoantigens (ASNEOs) from RNA-seq data.
  • To validate ASNEO's capability in identifying MHC I-presented neopeptides.
  • To explore the clinical relevance of ASNEOs in cancer immunotherapy.

Main Methods:

  • Development of the ASNEO pipeline for alternative splicing neoantigen identification.
  • Validation using mass spectrometry data for MHC I presentation.
  • Application of ASNEO to immunotherapy-treated patient cohorts.

Main Results:

  • ASNEO successfully identified neopeptides presented by MHC I.
  • Alternative splicing-based neopeptides exhibited higher immune scores compared to somatic neoantigens.
  • ASNEOs demonstrated potential as biomarkers for predicting patient survival.

Conclusions:

  • ASNEO enhances the understanding of the tumor immune landscape by including alternative splicing-derived neoantigens.
  • ASNEOs represent a promising avenue for developing personalized cancer vaccines.
  • The identification of ASNEOs contributes to more comprehensive neoantigen discovery for cancer immunotherapy.

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