Parameterized quantum circuits (PQCs) provide a flexible substrate for hybrid quantum machine learning (QML), but their practical value on Noisy Intermediate-Scale Quantum (NISQ) devices remains an empirical question, especially because training depth and scale can introduce optimization challenges such as barren plateaus. Here we study how the number and topology of two-qubit entangling gates in the feature-map stage influence a fixed hybrid QNN workflow for classifying strong versus weak epitope-receptor binding in Porcine Reproductive and Respiratory Syndrome (PRRS) vaccine design. The dataset consists of docking-derived binding affinities for N=80 9-mer epitopes, labeled as Strong or Weak binding, and partitioned into training, validation, and test subsets using a 40:30:30 split. We compare a classical CNN benchmark with a hybrid Embedding-QNN architecture under four feature-map configurations: a non-entangling Z feature map, an all-to-all high-entanglement ZZ feature map, and two interleaved nearest-neighbour entanglement patterns of low and high depth. Among the configurations tested, the high-entanglement ZZ feature map is seen to provide the strongest evidence of reduced training-set overfit, with a lower training area under the accuracy curve (AUAC) and the highest test/training AUAC ratio, while preserving competitive test-set accuracy. These results do not establish a general QML advantage, but they suggest that feature-map entanglement topology is a meaningful design variable for sparse biological screening tasks and warrants further evaluation with additional metrics, larger datasets, and noise-aware or hardware-based experiments.
Parameterized quantum circuits (PQCs) provide a flexible substrate for hybrid quantum machine learning (QML), but their practical value on Noisy Intermediate-Scale Quantum (NISQ) devices remains an empirical question, especially because training depth and scale can introduce optimization challenges such as barren plateaus. Here we study how the number and topology of two-qubit entangling gates in the feature-map stage influence a fixed hybrid QNN workflow for classifying strong versus weak epitope-receptor binding in Porcine Reproductive and Respiratory Syndrome (PRRS) vaccine design. The dataset consists of docking-derived binding affinities for N=80 9-mer epitopes, labeled as Strong or Weak binding, and partitioned into training, validation, and test subsets using a 40:30:30 split. We compare a classical CNN benchmark with a hybrid Embedding-QNN architecture under four feature-map configurations: a non-entangling Z feature map, an all-to-all high-entanglement ZZ feature map, and two interleaved nearest-neighbour entanglement patterns of low and high depth. Among the configurations tested, the high-entanglement ZZ feature map is seen to provide the strongest evidence of reduced training-set overfit, with a lower training area under the accuracy curve (AUAC) and the highest test/training AUAC ratio, while preserving competitive test-set accuracy. These results do not establish a general QML advantage, but they suggest that feature-map entanglement topology is a meaningful design variable for sparse biological screening tasks and warrants further evaluation with additional metrics, larger datasets, and noise-aware or hardware-based experiments.
Quantum machine learning has emerged as a promising approach to enhance computational efficiency by leveraging the principles of quantum computing. However, the limitations of current Noisy Intermediate-Scale Quantum (NISQ) devices, such as noise, limited qubit availability, and circuit depth constraints, restrict the implementation of fully quantum models. To address these challenges, this study focuses on the design, implementation, and performance evaluation of hybrid quantum-classical machine learning (HQML) models. The proposed approach integrates parameterized quantum circuits with classical optimization techniques to enable efficient learning within NISQ environments. The study employs standard benchmark datasets, including Iris, Breast Cancer, and MNIST, to evaluate the performance of the hybrid model. The results indicate that the HQML model achieves competitive accuracy on small and medium-sized datasets while maintaining balanced precision, recall, and F1-score. However, performance declines for complex datasets due to hardware limitations and noise effects. Additionally, the hybrid model demonstrates a lower number of parameters compared to classical deep learning models but requires higher training time due to iterative quantum-classical optimization. The findings highlight that hybrid quantum-classical models provide a practical and scalable approach for utilizing quantum computing in the current technological landscape. Although challenges related to noise, scalability, and computational overhead persist, advancements in quantum hardware and algorithm design are expected to improve performance. This study contributes to the growing field of quantum machine learning by providing a systematic framework for evaluating hybrid models on NISQ devices and identifying key areas for future research.
Designing parameterized quantum circuits (PQCs) that are expressive, trainable, and robust to hardware noise is a central challenge for quantum machine learning (QML) on noisy intermediate-scale quantum (NISQ) devices. We present a Domain-Aware Quantum Circuit (DAQC) that leverages image priors to guide locality-preserving encoding and entanglement via non-overlapping DCT-style zigzag windows. The design employs interleaved encode-entangle-train cycles, where entanglement is applied among qubits hosting neighboring pixels, aligned to device connectivity. This staged, locality-preserving information flow expands the effective receptive field without deep global mixing, enabling efficient use of limited depth and qubits. The design concentrates representational capacity on short-range correlations, reduces long-range two-qubit operations, and encourages stable optimization, thereby mitigating depth-induced and globally entangled barren-plateau effects. We evaluate DAQC on MNIST, FashionMNIST, and PneumoniaMNIST datasets. On quantum hardware, DAQC achieves performance competitive with strong classical baselines (e.g., ResNet-18/50, DenseNet-121, EfficientNet-B0) and substantially outperforming Quantum Circuit Search (QCS) baselines. To the best of our knowledge, DAQC, which uses a quantum feature extractor with only a linear classical readout (no deep classical backbone), currently achieves the best reported performance on real quantum hardware for QML-based image classification tasks. Code and pretrained models are available at: https://github.com/gurinder-hub/DAQC.
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.
Hybrid quantum-classical computing offers a promising pathway to harness quantum advantages while mitigating the hardware limitations of noisy intermediate-scale quantum (NISQ) devices. This work proposes a modular hybrid architecture that combines classical preprocessing, quantum-enhanced feature mapping through parameterized quantum circuits (PQCs), and adaptive classical optimization. The framework is designed to improve robustness and generalization of machine learning models in noisy environments, addressing critical issues such as overfitting, noise sensitivity, and hardware-induced errors. Experimental evaluations were conducted on benchmark datasets, including Iris, reduced-dimension MNIST, synthetic noisy XOR, Wine Quality, and Breast Cancer Wisconsin. The proposed model was tested under multiple noise models, such as Gaussian, salt-and-pepper, Poisson, and quantum-specific errors (bit-flip, phase-flip, and depolarizing), using 5-fold cross-validation and repeated trials for statistical rigor. Key performance metrics included Classification Accuracy (CA), Robustness Index (RI), and Training Stability (TS), with results reported as mean ± standard deviation and supported by paired t-tests (p < 0.05). Results demonstrate that the hybrid model consistently outperforms classical support vector machines (SVM) and standalone variational quantum classifiers (VQC) in noisy conditions, achieving smaller accuracy degradation and higher stability. The combination of quantum- enhanced feature mapping, optimizer synergy, and modular design is shown to be central to its resilience.
Abstract—Quantum Machine Learning (QML) operating on Noisy Intermediate-Scale Quantum (NISQ) hardware represents an emerging computational paradigm to address high-dimensional optimization problems that challenge classical Von Neumann supercomputing architectures. By mapping complex feature vectors into exponentially large 2^N Hilbert state spaces via Parameterized Quantum Circuits (PQCs) and Variational Quantum Algorithms (VQAs), QML targets computational advantages in combinatorial optimization, high-dimensional classification, and quantum-enhanced molecular modeling. However, the theoretical promise of NISQ-era variational computing is severely constrained by three fundamental bottlenecks: (1) Barren Plateaus, characterized by the exponential concentration of measure and vanishing variance of cost function gradients; (2) Hardware Decoherece Noise and readout error rates that corrupt quantum state fidelity; and (3) Classical-to-Quantum State Preparation bottlenecks that can erase theoretical computational speedups. This paper delivers an exhaustive, mathematically formal technical investigation and empirical benchmark of QML architectures for high-dimensional optimization. We formalize the Haar-distributed geometric mechanics of barren plateaus under 2-design unitary assumptions, evaluate barren plateau mitigation through shallow local cost operators and layer-by-layer parameter initialization, and contrast Variational Quantum Eigensolvers (VQE) with Quantum Kernel Support Vector Machines (Q-SVM). Furthermore, we construct an empirical benchmarking testbed executing across both state-vector simulators and superconducting quantum backends (IBM Quantum Heron / Eagle architectures), evaluating 127-qubit Hamiltonian optimization and high-dimensional financial portfolio allocation. Our findings demonstrate that while global cost functions suffer exponential gradient decay Var[grad] ~ O(2^-N) across circuit depth d >= 4, local Hamiltonian decomposition maintains trainable variance, achieving a 98.2% ground-state fidelity under zero-noise extrapolation (ZNE) error mitigation. Finally, we formulate open challenges in quantum error mitigation scaling, non-perturbative barren plateau escapes, and quantum data loading efficiency. Index Terms—Quantum Machine Learning (QML), Parameterized Quantum Circuits (PQCs), Variational Quantum Eigensolver (VQE), Barren Plateaus, Quantum Kernel Methods, NISQ Computing, Error Mitigation, Hilbert Space.
This study presents a comparative empirical evaluation of Variational Quantum Classifier (VQC) performance within the Quantum Machine Learning (QML) framework, focusing on VQC architectural analysis under NISQ-era qubit constraints. The VQC was designed utilizing ZFeatureMap for data encoding and EfficientSU2 as the ansatz. A systematic test was performed to evaluate the impact of three entanglement topologies (default, circular, pairwise) and two qubit scales (4 and 8) with four classical optimizers on standard classification datasets: Iris, Wine, and Breast Cancer. The results demonstrated that no single configuration is universally optimal. The default topology achieved the highest peak accuracy on multi-class datasets (Iris: 97% with P-BFGS), suggesting its efficiency in simpler parameter landscapes. Conversely, the pairwise and circular topologies showed superior stability and competitive accuracy (up to 92%) on the high-dimensional Breast Cancer dataset, confirming that richer qubit connectivity is essential for effective feature separation in more complex classification problems. Increasing the scale from 4 to 8 qubits was found to be crucial for improving the overall stability and consistency of performance rather than merely increasing peak accuracy. These findings provide essential empirical guidance for designing optimal and trainable VQC architectures under current quantum device limitations.