Patient classification using single-cell RNA-sequencing data with deep learning convolutional neural networks

Abstract

Single-cell RNA sequencing (scRNA-seq) enables gene expression profiling at the resolution of individual cells, revealing cellular heterogeneity that is obscured in bulk RNA-seq. While this offers a powerful lens to study disease-specific changes, leveraging scRNA-seq data for patient phenotype classification remains challenging due to limited sample numbers, cell count variability, high dimensionality, and dependence on cell-type annotations. Existing tools attempt to address these issues using probabilistic models or attention mechanisms, but face limitations in scalability, interpretability, or representational power. In this work, we introduce DeepCelllify, a novel deep learning-based framework that harnesses convolutional neural networks (CNNs) to classify patients using their individual cell expression profiles. Our approach converts tabular gene expression data into image-like representations, enabling CNNs to learn spatial feature relationships between genes. Each cell is treated as an independent input labeled by its originating patient’s condition (e.g., disease or control), allowing us to sidestep the limitations posed by small patient cohorts and heterogeneous cell counts. The DeepCelllify pipeline includes a transformation module for data preprocessing and a classification module, culminating in CNN models trained through cross-validation to differentiate between disease states based on single-cell inputs. Our method demonstrates competitive performance compared to state-of-the-art approaches, with added benefits in scalability, interpretability, and practical applicability. DeepCelllify further addresses critical bottlenecks in scRNA-seq-based phenotype prediction, including overfitting from low patient counts, challenges in feature matrix construction, and dimensionality issues. Additionally, our method provides interpretability by assigning weights to individual cells, helping to down-weight misclassified or noisy cells. This work introduces deep learning framework for patient phenotype prediction from scRNA-seq data, with potential applications in precision medicine and biomarker discovery.