TransAnno-Net: A Deep Learning Framework for Accurate Cell Type Annotation of Mouse Lung Tissue Using Self-supervised Pretraining.

Background: Single-cell RNA sequencing (scRNA-seq) has become a significant tool for addressing complex issuess in the field of biology. In the context of scRNA-seq analysis, it is imperative to accurately determine the type of each cell. However, conventional supervised or semi-supervised methodologies are contingent on expert labels and incur substantial labeling costs, In contrast self-supervised pre-training strategies leverage unlabeled data during the pre-training phase and utilise a limited amount of labeled data in the fine-tuning phase, thereby greatly reducing labor costs. Furthermore, the fine-tuning does not need to learn the feature representations from scratch, enhancing the efficiency and transferability of the model.

Methods: The proposed methodology is outlined below. The deep learning framework, TransAnno-Net, is based on transfer learning and a Transformer architecture. It has been designed for efficient and accurate cell type annotations in large-scale scRNA-seq datasets of mouse lung organs. Specifically, TransAnno-Net is pre-trained on the scRNA-seq lung data of approximately 100,000 cells to acquire gene-gene similarities via self-supervised learning. It is then migrated to a relatively small number of datasets to fine-tune specific cell type annotation tasks. To address the issue of imbalance in cell types commonly observed in scRNA-seq data, we applied a random oversampling technique is applied to the fine-tuned dataset. This is done to mitigate the impact of distributional imbalance on the annotation outcomes.

Results: The experimental findings demonstrate that TransAnno-Net exhibits superior performance with an AUC of 0.979, 0.901, and 0.982, respectively, on three mouse lung datasets, outperforming eight state-of-the-art (SOTA) methods. In addition, TransAnno-Net demonstrates robust performance on cross-organ, cross-platform datasets, and is competitive with the fully supervised learning-based method.

Conclusion: The TransAnno-Net method is a highly effective cross-platform and cross-data set single-cell type annotation method for mouse lung tissues and supports cross-organ cell type annotation. This approach is expected to enhance the efficiency of research on the biological mechanisms of complex biological systems and diseases.