cfDiffusion: diffusion-based efficient generation of high quality scRNA-seq data with classifier-free guidance

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Abstract
Single-cell RNA sequencing (scRNA-seq) technology provides a powerful means to measure gene expression at the individual cell level, thereby uncovering the intricate cellular heterogeneity that underlies various biological processes, including embryonic development, tumor metastasis, and microbial reproduction. However, the variable amounts of data generated across different cell types within tissues can compromise the accuracy of downstream analyses. Traditional approaches for generating scRNA-seq simulation data often rely on predefined data distributions, which can negatively impact the quality of the simulated data. Furthermore, these methods typically focus on simulating single-attribute cells, necessitating substantial additional data for the simulation of multi-attribute cells, which can lead to increased training times. To address these limitations, we propose cfDiffusion, a novel method grounded in diffusion models that incorporates Classifier-Free Guidance and a high-level feature caching mechanism. By leveraging Classifier-Free Guidance, cfDiffusion significantly reduces the training costs associated with model development compared to traditional Classifier Guidance methods. The integration of a caching mechanism further enhances efficiency by shortening inference times. While the inference duration of cfDiffusion remains longer than that of scDiffusion, it exhibits superior expressiveness and efficiency in generating multi-attribute single-cell data. Evaluated across datasets from multiple sequencing platforms, cfDiffusion consistently outperforms state-of-the-art models across various performance metrics. Additionally, cfDiffusion enables the simulation of single-cell data along a pseudo-time scale, facilitating advanced analyses such as tracking cell differentiation, investigating intercellular communication, and elucidating cellular heterogeneity.
Funding Information
  • National Science Foundation for Distinguished Young Scholars of China (62225109)
  • Natural Science Foundation of Heilongjiang Province, China (LH2024F003)
  • National Natural Science Foundation of China (62172087, 62473094)

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