Single-cell RNA sequencing data imputation using bi-level feature propagation

Abstract

Abstract Single-cell RNA sequencing (scRNA-seq) enables the exploration of cellular heterogeneity by analyzing gene expression profiles in complex tissues. However, scRNA-seq data often suffer from technical noise, dropout events and sparsity, hindering downstream analyses. Although existing works attempt to mitigate these issues by utilizing graph structures for data denoising, they involve the risk of propagating noise and fall short of fully leveraging the inherent data relationships, relying mainly on one of cell–cell or gene–gene associations and graphs constructed by initial noisy data. To this end, this study presents single-cell bilevel feature propagation (scBFP), two-step graph-based feature propagation method. It initially imputes zero values using non-zero values, ensuring that the imputation process does not affect the non-zero values due to dropout. Subsequently, it denoises the entire dataset by leveraging gene–gene and cell–cell relationships in the respective steps. Extensive experimental results on scRNA-seq data demonstrate the effectiveness of scBFP in various downstream tasks, uncovering valuable biological insights.