Revolutionizing Personalized Cancer Vaccines with NEO: Novel Epitope Optimization Using an Aggregated Feed Forward and Recurrent Neural Network with LSTM Architecture

TL;DR

This paper introduces NEO, a neural network-based tool combining feed forward and LSTM RNN architectures to improve the speed and accuracy of neoepitope binding predictions for personalized cancer vaccines.

Contribution

NEO integrates ensemble scoring with neural network architectures to enhance neoepitope prediction accuracy and efficiency for personalized cancer immunotherapy.

Findings

Achieved an AUC of 0.9166 in predictions

Recall rate of 91.67% for neoepitope binding

Combines FFNN and LSTM RNN for improved analysis

Abstract

As cancer cases continue to rise, with a 2023 study from Zhejiang and Harvard predicting a 31 percent increase in cases and a 21 percent increase in deaths by 2030, the need to find more effective treatments for cancer is greater than ever before. Traditional approaches to treating cancer, such as chemotherapy, often kill healthy cells because of their lack of targetability. In contrast, personalized cancer vaccines can utilize neoepitopes - distinctive peptides on cancer cells that are often missed by the body's immune system - that have strong binding affinities to a patient's MHC to provide a more targeted treatment approach. The selection of optimal neoepitopes that elicit an immune response is a time-consuming and costly process due to the required inputs of modern predictive methods. This project aims to facilitate faster, cheaper, and more accurate neoepitope binding predictions using Feed Forward Neural Networks (FFNN) and Recurrent Neural Networks (RNN). To address this, NEO was created. NEO requires next-generation sequencing data and uses a stacking ensemble method by calculating scores from state-of-the-art models (MHCFlurry 1.6, NetMHCstabpan 1.0, and IEDB). The model's architecture includes an FFNN and an RNN with LSTM layers capable of analyzing both sequential and non-sequential data. The results from both models are aggregated to produce predictions. Using this model, personalized cancer vaccines can be produced with improved results (AUC = 0.9166, recall = 91.67 percent).