Gene-Gene Relationship Modeling Based on Genetic Evidence for Single-Cell RNA-Seq Data Imputation

Single-cell RNA sequencing (scRNA-seq) technologies enable the exploration of cellular heterogeneity and facilitate the construction of cell atlases. However, scRNA-seq data often contain a large portion of missing values (false zeros) or noisy values, hindering downstream analyses. To recover these false zeros, propagation-based imputation methods have been proposed using k-NN graphs. However they model only associating relationships among genes within a cell, while, according to well-known genetic evidence, there are both associating and dissociating relationships among genes. To apply this genetic evidence to gene-gene relationship modeling, this paper proposes a novel imputation method that newly employs dissociating relationships in addition to associating relationships. Our method constructs a k-NN graph to additionally model dissociating relationships via the negation of a given cell-gene matrix. Moreover, our method standardizes the value distribution (mean and variance) of each gene to have standard distributions regardless of the gene. Through extensive experiments, we demonstrate that the proposed method achieves exceptional performance gains over state-of-the-art methods in both cell clustering and gene expression recovery across six scRNA-seq datasets, validating the significance of using complete gene-gene relationships in accordance with genetic evidence. The source code is available at https: //github.com/daehoum1/scCR.