Peptide Vaccine Design by Evolutionary Multi-Objective Optimization

TL;DR

This paper introduces PVD-EMO, a novel evolutionary multi-objective optimization framework for peptide vaccine design that balances maximizing immune response coverage with minimizing peptide count, outperforming greedy algorithms.

Contribution

It reformulates peptide vaccine design as a bi-objective optimization problem and incorporates strategies to improve efficiency and solution quality.

Findings

PVD-EMO outperforms greedy algorithms in experiments.

Warm-start strategy maintains approximation guarantees.

Framework effectively addresses peptide selection for COVID-19 vaccine.

Abstract

Peptide vaccines are growing in significance for fighting diverse diseases. Machine learning has improved the identification of peptides that can trigger immune responses, and the main challenge of peptide vaccine design now lies in selecting an effective subset of peptides due to the allelic diversity among individuals. Previous works mainly formulated this task as a constrained optimization problem, aiming to maximize the expected number of peptide-Major Histocompatibility Complex (peptide-MHC) bindings across a broad range of populations by selecting a subset of diverse peptides with limited size; and employed a greedy algorithm, whose performance, however, may be limited due to the greedy nature. In this paper, we propose a new framework PVD-EMO based on Evolutionary Multi-objective Optimization, which reformulates Peptide Vaccine Design as a bi-objective optimization problem that maximizes the expected number of peptide-MHC bindings and minimizes the number of selected peptides simultaneously, and employs a Multi-Objective Evolutionary Algorithm (MOEA) to solve it. We also incorporate warm-start and repair strategies into MOEAs to improve efficiency and performance. We prove that the warm-start strategy ensures that PVD-EMO maintains the same worst-case approximation guarantee as the previous greedy algorithm, and meanwhile, the EMO framework can help avoid local optima. Experiments on a peptide vaccine design for COVID-19, caused by the SARS-CoV-2 virus, demonstrate the superiority of PVD-EMO.