scDiffCom – a tool for differential analysis of cell–cell interactions from single-cell transcriptomics data

Dysregulation of intercellular communication is a hallmark of aging. To better quantify and explore changes in intercellular communication, University of Liverpool researchers have developed scDiffCom and scAgeCom. scDiffCom is an R package, relying on approximately 5,000 curated ligand-receptor interactions, that performs differential intercellular communication analysis between two conditions from single-cell transcriptomics data. Built upon scDiffCom, scAgeCom is an atlas of age-related cell-cell communication changes covering 23 mouse tissues from 58 single-cell RNA sequencing datasets from Tabula Muris Senis and the Calico murine aging cell atlas. It offers a comprehensive resource of tissue-specific and sex-specific aging dysregulations and highlights age-related intercellular communication changes widespread across the whole body, such as the upregulation of immune system processes and inflammation, the downregulation of developmental processes, angiogenesis and extracellular matrix organization and the deregulation of lipid metabolism. Our analysis emphasizes the relevance of the specific ligands, receptors and cell types regulating these processes.

Workflow summary of scDiffCom

Fig. 2

Read counts/UMIs from the single-cell dataset are aggregated by cell types and conditions (1). Genes are then joined with our database of LRIs (2) to build all the potential CCIs that can occur between cell types (3). Statistical permutation tests are then performed to evaluate the biological significance of each CCI and its differential expression (4). They are then classified based on several computed variables, such as their scores, P values and log fold change (5). Results are returned in a convenient format for downstream analyses and interpretation (6). FC, fold change; tSNE, t-distributed stochastic neighbor embedding.

Availability – The scAgeCom atlas is available at: The R package scDiffCom is available at:

Lagger C, Ursu E, Equey A, Avelar RA, Pisco AO, Tacutu R, de Magalhães JP. (2023) scDiffCom: a tool for differential analysis of cell-cell interactions provides a mouse atlas of aging changes in intercellular communication. Nat Aging [Epub ahead of print]. [article]

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