No cell is an island. All cells interact with others to build higher-order phenotypes. To enable the study of complex cell-cell interactions from omics data, we have developed the cell2cell package. This includes two main sub-tools:

• The regular cell2cell, which includes the main approaches described here (Armingol*, Officer*, et al. Nat Rev Genetics, 2021).
• Tensor-cell2cell, a novel method that uses tensor factorization to deconvolve patterns of cell-cell communication across multiple cellular contexts (e.g., time points, disease states, cellular location, patients, etc.) (see Armingol*, Baghdassarian*, et al., Nature Communications, 2022).

Project link: https://earmingol.github.io/cell2cell/

cell2cell is a user-friendly tool to infer cell-cell interactions and communication from gene expression of interacting proteins. It allows the use of both bulk and single-cell data, and uses any list of ligand-receptor interactions and a selection of computational methods for analyzing the intercellular interactions. Cell2cell also includes multiple visualization options that facilitate the interpretation of results.
Example of application in C. elegans: https://github.com/LewisLabUCSD/Celegans-cell2cell

Tensor-cell2cell is an unsupervised method using tensor decomposition, which allows one to decipher 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. This dimensionality reduction approach is able to use scores from any other tool for inferring cell-cell interactions and communication, and detect context-driven patterns from these scores.
It is implemented as part of our cell2cell suite, along with Tutorials and Documentation: https://earmingol.github.io/cell2cell/

• Jupyter notebooks for reproducing the results in the manuscript of Tensor-cell2cell are available and can be run online in codeocean.com.
• Detailed tutorials for running Tensor-cell2cell and downstream analyses: Obtaining patterns of cell-cell communication with Tensor-cell2cell
• Downstream analysis 1: Factor-specific analyses
• Downstream analysis 2: Gene Set Enrichment Analysis
• Do you have precomputed communication scores? Re-use them as a prebuilt tensor as exemplified here. This allows reusing previous tensors you built or even plugging in communication scores from other tools.
• Run Tensor-cell2cell much faster! An example to perform the analysis using a NVIDIA GPU is available here