ESCFD: Probabilistic Flow Diffusion Model for Accelerated High-Quality Single-Cell RNA-seq Data Synthesis

Single-cell RNA sequencing (scRNA-seq) technology has emerged as a powerful tool for studying complex biological systems and diseases with high resolution. However, generating sufficient high quality scRNA-seq samples for accurate downstream analyses and ensuring reproducibility remains a challenge. Previous methods often produce low-quality samples or a limited number of useful specific cell subpopulations. To address this issue, we propose a novel Efficient Single-Cell RNA-seq Flow Diffusion (named ESCFD) method based on the Diffusion Model, capable of synthesizing large-scale, high-quality scRNA-seq samples and generating either ''holistic'' or specific cellular subpopulations within a single framework. A pre-guidance mechanism is designed for synthesizing specific cellular subpopulations of high quality, and a post-guidance mechanism was designed to accelerate the sampling of scRNA-seq samples. The ESCFD can efficiently synthesize large-scale and high-quality scRNA-seq samples for various downstream tasks, surpassing previous work with faster sampling speed. Experimental results demonstrate that the ESCFD model achieves state-of-the-art performance in cell classification and cell distribution similarity when evaluated on three scRNA-seq benchmarks, and verified the effectiveness of accelerated sampling. Visualization experiments also reveal the ESCFD's ability to synthesize specific cellular subpopulations. This innovative approach has the potential to significantly advance our understanding of complex biological systems and accelerate the development of novel therapeutic interventions and personalized medicine strategies.