biostudies-literatureArmingol ELilly Innovation Fellows AwardPew Charitable TrustsW. M. Keck FoundationJ Yang Foundation FellowshipAgencia Nacional de Investigación y DesarrolloJefferson Foundation AwardNational Institute of General Medical SciencesSiebel Scholars FoundationNIGMS NIH HHSFulbright Chile Commissione1010715https://www.ebi.ac.uk/biostudies/studies/S-EPMC9714814biostudies-literatureUnknown18(11)Cell-cell interactions shape cellular function and ultimately organismal phenotype. Interacting cells can sense their mutual distance using combinations of ligand-receptor pairs, suggesting the existence of a spatial code, i.e., signals encoding spatial properties of cellular organization. However, this code driving and sustaining the spatial organization of cells remains to be elucidated. Here we present a computational framework to infer the spatial code underlying cell-cell interactions from the transcriptomes of the cell types across the whole body of a multicellular organism. As core of this framework, we introduce our tool cell2cell, which uses the coexpression of ligand-receptor pairs to compute the potential for intercellular interactions, and we test it across the Caenorhabditis ePLoS computational biologyInferring a spatial code of cell-cell interactions across a whole animal body.PMC9714814R35 GM119850DOCTORADO BECAS CHILE/2018 - 72190270Shamie IBerhanu SChan JJoshi CJArmingol EHer HLLewis NEBaghdassarian HGhaddar ARodriguez-Armstrong FYang ODar AO'Rourke EJfalseInferring a spatial code of cell-cell interactions across a whole animal body.Cell-cell interactions shape cellular function and ultimately organismal phenotype. Interacting cells can sense their mutual distance using combinations of ligand-receptor pairs, suggesting the existence of a spatial code, i.e., signals encoding spatial properties of cellular organization. However, this code driving and sustaining the spatial organization of cells remains to be elucidated. Here we present a computational framework to infer the spatial code underlying cell-cell interactions from the transcriptomes of the cell types across the whole body of a multicellular organism. As core of this framework, we introduce our tool cell2cell, which uses the coexpression of ligand-receptor pairs to compute the potential for intercellular interactions, and we test it across the Caenorhabditis e2022-01-01T00:00:00Z2022 Nov2025-04-26T12:31:14.299Z2025-04-06T14:01:03.935ZS-EPMC97148143639533110.1371/journal.pcbi.1010715