OmniNeo: a multi-omics pipeline incorporating proteomics and AI selection for neoantigen optimization in tumor

Manman Lu1,2, Yang Liu2, Linfeng Xu3

  • 1College of Food Science and Technology, Shanghai Ocean University, Shanghai, China.

Frontiers in Immunology
|January 2, 2026
PubMed

Insights

OmniNeo is a new framework for discovering cancer neoantigens using multi-omics data. It improves immunogenicity prediction and offers a scalable, portable solution for cancer immunotherapy development.

Area of Science:

  • Cancer immunotherapy
  • Genomics and Bioinformatics
  • Precision Medicine

Background:

  • Neoantigen-based vaccines are promising for cancer immunotherapy.
  • Current neoantigen identification methods lack multi-omics integration and robust filtering, limiting immunogenicity assessment and clinical applicability.
  • Complexity and poor portability of existing tools hinder widespread clinical use.

Purpose of the Study:

  • To develop an automated, multi-omics framework for comprehensive neoantigen discovery.
  • To enhance the prediction of immunogenic neoantigens by integrating diverse data types and advanced computational models.
  • To provide a scalable, portable, and user-friendly solution for rapid neoantigen identification.

Main Methods:

  • OmniNeo integrates whole-genome/exome sequencing (WGS/WES), transcriptomic, and proteomics data.
  • Identifies neoantigenic epitopes from various genetic variations including SNVs/Indels, frameshift mutations, gene fusions, and non-coding region variations.
  • Employs a convolutional neural network (OmniNeo-CNN) and multiple filtering steps to quantify immunogenicity and T-cell receptor (TCR) recognition potential.
  • Utilizes Nextflow for a scalable and portable workflow.

Main Results:

  • OmniNeo successfully integrates multi-omics data for comprehensive neoantigen identification.
  • The OmniNeo-CNN model effectively quantifies neoantigen immunogenicity and TCR recognition potential.
  • The Nextflow-based workflow provides a rapid, scalable, and portable solution for neoantigen prediction.
  • Demonstrated practical application in liver cancer samples for potential immunotherapy.

Conclusions:

  • OmniNeo offers an advanced, automated framework for discovering immunogenic neoantigens by leveraging multi-omics data.
  • The tool addresses limitations of existing methods, improving the accuracy and efficiency of neoantigen prediction for cancer immunotherapy.
  • OmniNeo is an open-source resource, facilitating its accessibility and application in clinical research and development.

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