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NeoDesign: a Computational Tool for Optimal Selection of Polyvalent Neoantigen Combinations

Overview
Journal Bioinformatics
Specialty Biology
Date 2024 Sep 27
PMID 39331572
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Abstract

Motivation: Tumor polyvalent neoantigen mRNA vaccines are gaining prominence in immunotherapy. The design of sequences in vaccine development is crucial for enhancing both the immunogenicity and safety of vaccines. However, a major challenge lies in selecting the optimal sequences from the large pools generated by multiple peptide combinations and synonymous codons.

Results: We introduce NeoDesign, a computational tool designed to tackle the challenge of sequence design. NeoDesign comprises four modules: Library Construction, Optimal Path Filtering, Linker Addition, and λ-Evaluation. It aims to identify the optimal protein sequence for tumor polyvalent neoantigen vaccines by minimizing linker usage, avoiding unexpected neoantigens and functional domains, and simplifying the structure. It also provides a preference scheme to balance mRNA stability and protein expression when designing mRNA sequences for the optimal protein sequence. This tool can potentially improve the sequence design of tumor polyvalent neoantigen mRNA vaccines, thereby significantly advancing immunotherapy strategies.

Availability And Implementation: NeoDesign is freely available on https://github.com/HuangLab-Fudan/neoDesign and https://figshare.com/projects/NeoDesign/221704.

References
1.
Lata S, Mishra R, Banerjea A . Proteasomal Degradation Machinery: Favorite Target of HIV-1 Proteins. Front Microbiol. 2018; 9:2738. PMC: 6262318. DOI: 10.3389/fmicb.2018.02738. View

2.
Ott P, Hu-Lieskovan S, Chmielowski B, Govindan R, Naing A, Bhardwaj N . A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell Lung Cancer, or Bladder Cancer. Cell. 2020; 183(2):347-362.e24. DOI: 10.1016/j.cell.2020.08.053. View

3.
Mei Y, Wang X . RNA modification in mRNA cancer vaccines. Clin Exp Med. 2023; 23(6):1917-1931. PMC: 9928499. DOI: 10.1007/s10238-023-01020-5. View

4.
Yadav M, Jhunjhunwala S, Phung Q, Lupardus P, Tanguay J, Bumbaca S . Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature. 2014; 515(7528):572-6. DOI: 10.1038/nature14001. View

5.
Prakash S, Tian L, Ratliff K, Lehotzky R, Matouschek A . An unstructured initiation site is required for efficient proteasome-mediated degradation. Nat Struct Mol Biol. 2004; 11(9):830-7. DOI: 10.1038/nsmb814. View