Context-aware deconvolution of cell–cell communication with Tensor-cell2cell

• Published in: Nature communications 2022-06, Vol.13 (1), p.3665-3665, Article 3665
• Main Authors: Armingol, Erick, Baghdassarian, Hratch M., Martino, Cameron, Perez-Lopez, Araceli, Aamodt, Caitlin, Knight, Rob, Lewis, Nathan E.
• Format: Article
• Language: English
• Subjects: 38; 631/114/2391; 631/114/2397; 631/114/2398; 631/1647/514/1949; Autism; Autism Spectrum Disorder; Cell Communication; Cell interactions; Cellular communication; Communication; Computer applications; Context; Coronaviruses; COVID-19; Developmental stages; Humanities and Social Sciences; Humans; Ligands; Mathematical analysis; Microenvironments; multidisciplinary; Phenotype; Phenotypes; Receptors; Science; Science (multidisciplinary); Software; Tensors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-31369-2

Cell interactions determine phenotypes, and intercellular communication is shaped by cellular contexts such as disease state, organismal life stage, and tissue microenvironment. Single-cell technologies measure the molecules mediating cell–cell communication, and emerging computational tools can exploit these data to decipher intercellular communication. However, current methods either disregard cellular context or rely on simple pairwise comparisons between samples, thus limiting the ability to decipher complex cell–cell communication across multiple time points, levels of disease severity, or spatial contexts. Here we present Tensor-cell2cell, an unsupervised method using tensor decomposition, which deciphers context-driven intercellular communication by simultaneously accounting for multiple stages, states, or locations of the cells. To do so, Tensor-cell2cell uncovers context-driven patterns of communication associated with different phenotypic states and determined by unique combinations of cell types and ligand-receptor pairs. As such, Tensor-cell2cell robustly improves upon and extends the analytical capabilities of existing tools. We show Tensor-cell2cell can identify multiple modules associated with distinct communication processes (e.g., participating cell–cell and ligand-receptor pairs) linked to severities of Coronavirus Disease 2019 and to Autism Spectrum Disorder. Thus, we introduce an effective and easy-to-use strategy for understanding complex communication patterns across diverse conditions. Cellular contexts such as disease state, organismal life stage and tissue microenvironment, shape intercellular communication, and ultimately affect an organism’s phenotypes. Here, the authors present Tensor-cell2cell, an unsupervised method for deciphering context-driven intercellular communication.