Assessing tissue-specific gene expression of essential genes from human and mouse.

Abstract

A gene satisfies the definition of essentiality when the loss of its function compromises an organisms viability. Identifying essential genes is useful for understanding the core components that regulate a biological system and ensure its survival. Advances in gene editing techniques like CRISPR-Cas9 generate the capacity to comprehensively interrogate a genome to elucidate what genes are essential. However, these techniques are often applied in the context of a single cell line and even when studies have collated essential gene sets across multiple cell lines, this information is rarely probed at a level that incorporates multiple cell and tissue types. The recent availability of large-scale single-cell RNA-sequencing (scRNA-seq) atlases provides an unprecedented opportunity to investigate the distribution of essential gene expression in cell and tissue types. Here, we leverage information contained in benchmarking datasets, single cell tissue atlases, and databases of essential genes, and develop a computational method, scEssentials, which uses a statistical framework to report on the robustness and specificity of essential genes in human and mouse across multiple cell types. Using scEssentials, both mouse and human models showed consistently high in expression and exhibit limited variably across more than 60 cell types. We also demonstrate a substantial number of significantly correlated gene pairs within scEssentials, which produce densely connected co-expression networks with functional annotation. Furthermore, we showed high frequencies of scEssentials across 200 pathways. Finally, we develop a score to quantify the relative essentiality of genes within scEssentials, which further validates with significant association with gene mutation frequency and chromatin accessibility. Using the heterogeneous ageing process, we demonstrate the application of scEssentials and their robust gene expression profile. Only one-fifth of scEssentials showed significant ageing-related differential expression among three age groups, occurring primarily in muscle satellite cells of varying tissue origins and highly interacting brain cells. Collectively, the robustness of scEssentials serves as a reference for analysing scRNA-seq data and provides insight into the heterogeneous nature of biological processes such as ageing.