{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:13:29Z","timestamp":1790144009217,"version":"4.0.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Cell-cell communication plays a critical role in tissue organization, development, immune regulation, and disease progression. Spatial transcriptomics enables the inference of such communication within the native tissue context. However, existing methods often rely on ligand\u2013receptor co-expression or spatial proximity alone, without explicitly modeling the directional nature of intercellular signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We propose CauSTI, a causal spatial transcriptomic interaction inference framework for identifying direction-specific cell-cell communication. CauSTI integrates spatial neighborhood structure with ligand\u2013receptor-derived causal priors through a causal-prior-guided variational graph autoencoder. Spatial proximity defines the tissue graph, while ligand\u2013receptor evidence provides biologically informed directional constraints. An asymmetric decoder models sender\u2013receiver relationships between ordered cell pairs. The optimization objective jointly incorporates spatial reconstruction, causal-prior consistency, variational regularization, and directional regularization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Experiments on three spatial transcriptomic datasets\u2014seqFISH+, MERSCOPE, and Xenium\u2014demonstrate that CauSTI consistently outperforms representative baseline methods in AUROC, ACC, and AP. Ablation studies further confirm the contributions of causal priors and directional regularization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings suggest that integrating spatial context with causal priors and explicit directional modeling provides an effective framework for inferring biologically plausible, direction-specific cell-cell communication landscapes from spatial transcriptomic data.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1943696","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:55:40Z","timestamp":1790142940000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CauSTI: causal spatial transcriptomic interaction inference for cell-cell communication"],"prefix":"10.3389","volume":"14","author":[{"given":"Hongjie","family":"Ji","sequence":"first","affiliation":[{"name":"Department of Information Security Technology, Jilin Police College","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Huang","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Lyu","sequence":"additional","affiliation":[{"name":"Faculty of Innovation Engineering, Macau University of Science and Technology","place":["Taipa, Macao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"RE9","DOI":"10.1126\/stke.2003.187.re9","article-title":"Signaling receptome: a genomic and evolutionary perspective of plasma membrane receptors involved in signal transduction","volume":"2003","author":"Ben-Shlomo","year":"2003","journal-title":"Science\u2019s STKE"},{"key":"B2","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/s41592-019-0667-5","article-title":"Nichenet: modeling intercellular communication by linking ligands to target genes","volume":"17","author":"Browaeys","year":"2020","journal-title":"Nat. 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