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Science Advances

Quantum convolutional HLA immunogenic peptide prediction (Q-CHIPP): Next-generation neoantigen prediction with quantum neural network

Ryan Peters, Kahn Rhrissorrakrai, Prerana Bangalore Parthasarathy, Vadim Ratner, Tanvi P. Gujarati, Meltem Tolunay, Jie Shi, Jeffrey K. Weber, Timothy An-thy Chan, Laxmi Parida, Sara Capponi, Filippo Utro, Tyler Joseph Alban

Published Jul 24, 2026• 0 citations
Publisher

Abstract

The rapid growth of quantum computing is driven by promises of performing complex calculations with unprecedented speed; however, current use cases have been limited by quantum hardware and the difficulty of identifying problems that classical computers cannot easily address. Within these constraints, biological problems including drug discovery, protein folding, and precision medicine present an opportunity to understand how current quantum hardware can make advances. In immunology, accurate prediction of cancer neoantigens remains a major challenge, limited by small, noisy datasets and the inability of classical models to generalize. In approaching the problem, we explore multiple noise mitigation techniques, including Pauli twirling and dynamical decoupling, in conjunction with controlled shot-based sampling to stabilize training on real hardware and in a warm start hybrid approach. With these approaches, we demonstrate the use of Quantum Convolutional Neural Networks (QCNNs) for both MHC binding and immunogenicity prediction, including a quantum hardware experiment involving 46 qubits that achieved a 6% increase in classification accuracy with fewer training samples compared to classical approaches. Building on these models, we introduce Quantum Convolutional HLA Immunogenic Peptide Prediction (Q-CHIPP), a combinatorial framework integrating MHC binding and T-cell recognition. It targets HLA-A*02:01-restricted 9-mer peptides and, more accurately, identifies those peptides known to be immunogenic, improving the prognostic impact of predicted neoantigen load. Together, these represent a large-scale application of QCNNs in biomedical modeling, highlighting both the feasibility and promise of quantum machine learning for data-limited biological systems and establishing a scalable foundation for quantum-enhanced biomedical research.

DOI
10.1126/sciadv.aec3824

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Quantum Convolutional HLA Immunogenic Peptide Prediction (Q-CHIPP): Next-Generation Neoantigen Prediction with Quantum Neural Networks

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arXiv:2509.11046•EPJ Quantum Technology•Oct 22, 2025•2 citations
The rapid growth of quantum computing is driven by promises of performing complex calculations with unprecedented speed; however, current use cases have been limited by quantum hardware and the difficulty of identifying problems that classical computers cannot easily address. Within these constraints, biological problems including drug discovery, protein folding, and precision medicine present an opportunity to understand how current quantum hardware can make advances. In immunology, accurate prediction of cancer neoantigens remains a major challenge, limited by small, noisy datasets and the inability of classical models to generalize. In approaching the problem, we explore multiple noise mitigation techniques, including Pauli twirling and dynamical decoupling, in conjunction with controlled shot-based sampling to stabilize training on real hardware and in a warm start hybrid approach. With these approaches, we demonstrate the use of Quantum Convolutional Neural Networks (QCNNs) for both MHC binding and immunogenicity prediction, including a quantum hardware experiment involving 46 qubits that achieved a 6% increase in classification accuracy with fewer training samples compared to classical approaches. Building on these models, we introduce Quantum Convolutional HLA Immunogenic Peptide Prediction (Q-CHIPP), a combinatorial framework integrating MHC binding and T-cell recognition. It targets HLA-A*02:01-restricted 9-mer peptides and, more accurately, identifies those peptides known to be immunogenic, improving the prognostic impact of predicted neoantigen load. Together, these represent a large-scale application of QCNNs in biomedical modeling, highlighting both the feasibility and promise of quantum machine learning for data-limited biological systems and establishing a scalable foundation for quantum-enhanced biomedical research.
ABSTRACT The immune system is an intricately evolved series of cellular and protein-protein interactions, which defend the body against pathogens and abnormal cells such as cancer. A key player in the immunologic recognition of non-self is the immune synapse, where T cell receptors (TCRs) scan peptides presented on major histocompatibility complex (MHC) molecules to detect and eliminate cells displaying non-self antigens. While this interaction is vital for vaccine and immunotherapy success, the underlying rules of TCR recognition remain poorly understood. This is only further challenged as the application of predictive models is very limited due to small training datasets. While traditional machine learning models excel at predicting neoantigen binding to MHC, they often struggle to accurately predict immunogenicity. To address these challenges, we developed a quantum computing approach using Quantum Convolutional Neural Networks (QCNNs). Here we present Quantum Convolutional Human Leukocyte Antigen (HLA) Immunogenic Peptide Prediction (Q-CHIPP), the first application of quantum hardware based on training/predicting both MHC binding and immunogenicity in a combinatorial approach. Additionally, we present a large scale use of quantum hardware at scale with 46 qubits. This study underscores how quantum technology can be used for biological modeling and presents a scalable QCNN design with the potential to overcome current computational bottlenecks as quantum hardware advances.
Peptide-HLA binding prediction is a critical step in neoantigen identification for personalized cancer immunotherapy and holds significant clinical value. However, the training data available for many HLA alleles are extremely limited, which severely constrains the performance of conventional methods on this task. Parameterized quantum circuits are hypothesized to induce inductive biases beneficial for learning from small datasets, yet their application to biological sequence prediction remains underexplored. To address this, we propose a hybrid quantum-classical neural network (HQNN) specifically designed for peptide-HLA binding prediction. HQNN integrates multi-source biological feature encoding with parallel quantum feature extractors and a quantum-enhanced classifier. On two HLA alleles (A*02:01 and B*07:02), HQNN outperforms a parameter-matched classical CNN baseline across all training sizes, with the performance gap widening as training data decreases. Ablation studies confirm the respective contributions of the quantum feature extraction module and the quantum classifier. In noise-aware simulations, performance degrades only mildly, and such degradation is reasonable and acceptable under realistic quantum hardware noise levels. These results suggest that hybrid quantum-classical architectures can provide practical sample-efficiency gains for immunoinformatics tasks in low-data regimes.
One of the main challenges in drug discovery is to find molecules that bind specifically and strongly to their target protein while having minimal binding to other proteins. By predicting binding affinity, it is possible to identify the most promising candidates from a large pool of potential compounds, reducing the number of compounds that need to be tested experimentally. Recently, deep learning methods have shown superior performance than traditional computational methods for making accurate predictions on large datasets. However, the complexity and time-consuming nature of these methods have limited their usage and development. Quantum machine learning is an emerging technology that has the potential to improve many classical machine learning algorithms. In this work we present a hybrid quantum-classical convolutional neural network, which is able to reduce by 20% the complexity of the classical network while maintaining optimal performance in the predictions. Additionally, it results in a significant time savings of up to 40% in the training process, which means a meaningful speed up of the drug discovery process.
Drug repositioning is a less expensive and time-consuming method than the traditional method of drug discovery. It is a strategy for identifying new uses for approved or investigational drugs that are outside the scope of the original medical indication. A key strategy in repositioning approved or investigational drugs is determining the binding affinity of these drugs to target proteins. The large increase in available experimental data has helped deep learning methods to demonstrate superior performance compared to conventional prediction and other traditional computational methods in precise binding affinity prediction. However, these methods are complex and time-consuming, presenting a significant barrier to their development and practical application. In this context, quantum computing (QC) and quantum machine learning (QML) theoretically offer promising solutions to effectively address these challenges. In this work, we introduce a hybrid quantum–classical framework to predict binding affinity. Our approach involves, initially, the implementation of an efficient classical model using convolutional neural networks (CNNs) for feature extraction and three fully connected layers for prediction. Subsequently, retaining the classical module for feature extraction, we implement various quantum and classical modules for binding affinity prediction, which accept the concatenated features as input. Quantum predicted modules are implemented with Variational Quantum Regressions (VQRs), while classical predicted modules are implemented with various fully connected layers. Our findings clearly show that hybrid quantum–classical models accelerate the training process in terms of epochs and achieve faster stabilization. Also, these models demonstrate quantum superiority in terms of complexity, accuracy, and generalization, thereby indicating a promising direction for QML.
Image classification plays a vital role in large-scale data analysis, especially in object recognition tasks using advanced Deep Learning (DL) frameworks. However, the growing complexity and computational demands of modern DL models have introduced challenges related to scalability and efficiency. Quantum Computing (QC) has emerged as a promising alternative, capable of addressing these limitations by leveraging the principles of Quantum Machine Learning (QML). However, many existing QML models require a large number of qubits, which poses limitations within the current Noisy Intermediate-Scale Quantum (NISQ) era. This work introduces a novel Adaptive Quantum Convolutional Neural Network (AQCNN) designed for efficient and scalable image classification within the constraints of NISQ devices. Addressing the limitations of existing QML approaches, particularly the high qubit requirements, AQCNN incorporates a resource-efficient quantum convolutional layer that performs localized quantum filtering using parameterized quantum circuits. A classical preprocessing layer encodes input features to reduce qubit load, followed by quantum embedding and hybrid quantum-classical layers that optimize feature extraction and classification performance. The model leverages an adaptive quantum convolution strategy, minimizing quantum gate depth and circuit complexity while preserving critical spatial hierarchies in image data. Evaluated on benchmark datasets, AQCNN achieved 95.88% accuracy on MNIST and 95.68% on FMNIST, outperforming comparable QML architectures. Additionally, the model supports scalable execution through parallel quantum circuit arrays, enabling practical deployment on current quantum hardware. This architecture demonstrates a significant advance in quantum-assisted image classification, balancing performance with qubit and gate efficiency. The integration of adaptive quantum convolution and hybrid processing not only enhances classification accuracy but also provides a viable path forward for deploying QML solutions under realistic hardware constraints.
Protein-ligand binding affinity is critical in drug discovery, but experimentally determining it is time-consuming and expensive. Artificial intelligence (AI) has been used to predict binding affinity, significantly accelerating this process. However, the high-performance requirements and vast datasets involved in affinity prediction demand increasingly large AI models, requiring substantial computational resources and training time. Quantum machine learning has emerged as a promising solution to these challenges. In particular, hybrid quantum-classical models can reduce the number of parameters while maintaining or improving performance compared to classical counterparts. Despite these advantages, challenges persist: why hybrid quantum models achieve these benefits, whether quantum neural networks (QNNs) can replace classical neural networks, and whether such models are feasible on noisy intermediate-scale quantum (NISQ) devices. This study addresses these challenges by proposing a hybrid quantum neural network (HQNN) that empirically demonstrates the capability to approximate non-linear functions in the latent feature space derived from classical embedding. The primary goal of this study is to achieve a parameter-efficient model in binding affinity prediction while ensuring feasibility on NISQ devices. Numerical results indicate that HQNN achieves comparable or superior performance and parameter efficiency compared to classical neural networks, underscoring its potential as a viable replacement. This study highlights the potential of hybrid QML in computational drug discovery, offering insights into its applicability and advantages in addressing the computational challenges of protein-ligand binding affinity prediction.