{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T08:04:37Z","timestamp":1772784277848,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1010715","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000}}],"reference-count":75,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020884","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["DOCTORADO BECAS CHILE\/2018 - 72190270"],"award-info":[{"award-number":["DOCTORADO BECAS CHILE\/2018 - 72190270"]}],"id":[{"id":"10.13039\/501100020884","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fulbright Chile Commission"},{"DOI":"10.13039\/100015597","name":"Siebel Scholars Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015597","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35 GM119850"],"award-info":[{"award-number":["R35 GM119850"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Lilly Innovation Fellows Award"},{"name":"Jefferson Foundation Award"},{"name":"J Yang Foundation Fellowship"},{"DOI":"10.13039\/100000875","name":"Pew Charitable Trusts","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000875","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000888","name":"W. M. Keck Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    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\n                    <jats:italic>cell2cell<\/jats:italic>\n                    , which uses the coexpression of ligand-receptor pairs to compute the potential for intercellular interactions, and we test it across the\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    \u2019 body. Leveraging a 3D atlas of\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>elegans<\/jats:italic>\n                    \u2019 cells, we also implement a genetic algorithm to identify the ligand-receptor pairs most informative of the spatial organization of cells across the whole body. Validating the spatial code extracted with this strategy, the resulting intercellular distances are negatively correlated with the inferred cell-cell interactions. Furthermore, for selected cell-cell and ligand-receptor pairs, we experimentally confirm the communicatory behavior inferred with\n                    <jats:italic>cell2cell<\/jats:italic>\n                    and the genetic algorithm. Thus, our framework helps identify a code that predicts the spatial organization of cells across a whole-animal body.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1010715","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T14:16:07Z","timestamp":1668694567000},"page":"e1010715","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":43,"title":["Inferring a spatial code of cell-cell interactions across a whole animal body"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1546-9165","authenticated-orcid":true,"given":"Erick","family":"Armingol","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8695-4694","authenticated-orcid":true,"given":"Abbas","family":"Ghaddar","sequence":"additional","affiliation":[]},{"given":"Chintan J.","family":"Joshi","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2739-8613","authenticated-orcid":true,"given":"Hratch","family":"Baghdassarian","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6122-2905","authenticated-orcid":true,"given":"Isaac","family":"Shamie","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1618-5516","authenticated-orcid":true,"given":"Jason","family":"Chan","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7691-3816","authenticated-orcid":true,"given":"Hsuan-Lin","family":"Her","sequence":"additional","affiliation":[]},{"given":"Samuel","family":"Berhanu","sequence":"additional","affiliation":[]},{"given":"Anushka","family":"Dar","sequence":"additional","affiliation":[]},{"given":"Fabiola","family":"Rodriguez-Armstrong","sequence":"additional","affiliation":[]},{"given":"Olivia","family":"Yang","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0503-4181","authenticated-orcid":true,"given":"Eyleen J.","family":"O\u2019Rourke","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7700-3654","authenticated-orcid":true,"given":"Nathan E.","family":"Lewis","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,11,17]]},"reference":[{"key":"pcbi.1010715.ref001","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1038\/s41580-020-00298-7","article-title":"Cell\u2013cell interfaces as specialized compartments directing cell function","volume":"21","author":"B Belardi","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"key":"pcbi.1010715.ref002","doi-asserted-by":"crossref","first-page":"12258","DOI":"10.1073\/pnas.94.23.12258","article-title":"Effective intercellular communication distances are determined by the relative time constants for cyto\/chemokine secretion and diffusion","volume":"94","author":"K Francis","year":"1997","journal-title":"Proc Natl Acad Sci U S 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Ren","year":"2020","journal-title":"Cell Res"},{"key":"pcbi.1010715.ref011","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/s41592-018-0009-z","article-title":"Mapping the physical network of cellular interactions","volume":"15","author":"J-C Boisset","year":"2018","journal-title":"Nat Methods"},{"key":"pcbi.1010715.ref012","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41556-019-0439-6","article-title":"Combined single-cell and spatial transcriptomics reveal the molecular, cellular and spatial bone marrow niche organization","volume":"22","author":"C Baccin","year":"2020","journal-title":"Nat Cell Biol"},{"key":"pcbi.1010715.ref013","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1038\/s41467-020-15968-5","article-title":"Inferring spatial and signaling relationships between cells from single cell transcriptomic data","volume":"11","author":"Z Cang","year":"2020","journal-title":"Nat 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Hussey","year":"2018","journal-title":"PLoS Genet"},{"key":"pcbi.1010715.ref039","first-page":"15","article-title":"Membrane-associated collagens with interrupted triple-helices (MACITs): evolution from a bilaterian common ancestor and functional conservation in C. elegans","author":"H Tu","year":"2015","journal-title":"BMC Evolutionary Biology"},{"key":"pcbi.1010715.ref040","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.ydbio.2006.06.050","article-title":"Multiple redundant Wnt signaling components function in two processes during C. elegans vulval development","volume":"298","author":"JE Gleason","year":"2006","journal-title":"Dev Biol"},{"key":"pcbi.1010715.ref041","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.cell.2007.06.046","article-title":"Wnt signaling positions neuromuscular connectivity by inhibiting synapse formation in C. elegans","volume":"130","author":"MP Klassen","year":"2007","journal-title":"Cell"},{"key":"pcbi.1010715.ref042","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0092-8674(95)90238-4","article-title":"The C. elegans gene lin-44, which controls the polarity of certain asymmetric cell divisions, encodes a Wnt protein and acts cell nonautonomously","volume":"83","author":"MA Herman","year":"1995","journal-title":"Cell"},{"key":"pcbi.1010715.ref043","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S1097-2765(00)80394-9","article-title":"A Wnt signaling system that specifies two patterns of cell migration in C. elegans","volume":"4","author":"J Whangbo","year":"1999","journal-title":"Mol Cell"},{"key":"pcbi.1010715.ref044","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.devcel.2006.02.010","article-title":"Multiple Wnts and frizzled receptors regulate anteriorly directed cell and growth cone migrations in Caenorhabditis elegans","volume":"10","author":"C-L 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Ginzburg","year":"2002","journal-title":"Development"},{"key":"pcbi.1010715.ref048","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1534\/genetics.106.067116","article-title":"The PLEXIN PLX-2 and the ephrin EFN-4 have distinct roles in MAB-20\/Semaphorin 2A signaling in Caenorhabditis elegans morphogenesis","volume":"176","author":"F Nakao","year":"2007","journal-title":"Genetics"},{"key":"pcbi.1010715.ref049","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S1534-5807(04)00057-7","article-title":"Integration of semaphorin-2A\/MAB-20, ephrin-4, and UNC-129 TGF-beta signaling pathways regulates sorting of distinct sensory rays in C. elegans","volume":"6","author":"R Ikegami","year":"2004","journal-title":"Dev Cell"},{"key":"pcbi.1010715.ref050","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ydbio.2005.03.002","article-title":"C. elegans PlexinA PLX-1 mediates a cell contact-dependent stop signal in vulval precursor cells","volume":"282","author":"Z Liu","year":"2005","journal-title":"Dev Biol"},{"key":"pcbi.1010715.ref051","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1083\/jcb.200704178","article-title":"The C. elegans L1CAM homologue LAD-2 functions as a coreceptor in MAB-20\/Sema2\u2013mediated axon guidance","volume":"180","author":"X Wang","year":"2008","journal-title":"J Cell Biol"},{"key":"pcbi.1010715.ref052","article-title":"Two new functions in the WormBase enrichment suite","author":"D Angeles-Albores","year":"2018","journal-title":"microPublication Biology"},{"key":"pcbi.1010715.ref053","doi-asserted-by":"crossref","first-page":"D463","DOI":"10.1093\/nar\/gkp952","article-title":"WormBase: a comprehensive resource for nematode research","volume":"38","author":"TW Harris","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1010715.ref054","doi-asserted-by":"crossref","first-page":"D480","DOI":"10.1093\/nar\/gkaa1100","article-title":"UniProt: the universal 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Tuck","year":"2014","journal-title":"Exp Cell Res"},{"key":"pcbi.1010715.ref058","doi-asserted-by":"crossref","first-page":"e1330246","DOI":"10.1080\/21624054.2017.1330246","article-title":"Molting in C. elegans","volume":"6","author":"V La\u017eeti\u0107","year":"2017","journal-title":"Worm"},{"key":"pcbi.1010715.ref059","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1534\/genetics.108.090290","article-title":"Complex network of Wnt signaling regulates neuronal migrations during Caenorhabditis elegans development","volume":"179","author":"AY Zinovyeva","year":"2008","journal-title":"Genetics"},{"key":"pcbi.1010715.ref060","first-page":"715912","article-title":"Gradient-independent Wnt signaling instructs asymmetric neurite pruning in C. elegans","author":"M Lu","year":"2019","journal-title":"bioRxiv"},{"key":"pcbi.1010715.ref061","doi-asserted-by":"crossref","first-page":"e1002308","DOI":"10.1371\/journal.pgen.1002308","article-title":"Multiple Wnts redundantly control 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