{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:34:35Z","timestamp":1772138075538,"version":"3.50.1"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Sydney and an Australian Research Council Discovery Early Career Researcher","award":["DE200100944"],"award-info":[{"award-number":["DE200100944"]}]},{"DOI":"10.13039\/100015539","name":"Australian Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015539","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>As research advances in spatially resolving the biological archetype of various diseases, technologies that capture the spatial relationships between cells are demonstrating increasing value. Whilst there are an increasing number of analytical methods being developed to identify the complex web of interactions between cells, the downstream impacts of these cell\u2013cell relationships are under explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We present SpatioMark, a statistical framework that simplifies the assessment of gene or protein expression changes within a cell type that are associated with the spatial proximity to other cell types. We demonstrate its performance across spatial proteomics and transcriptomics datasets. We link identified relationships with differences in patient survival. We highlight key challenges in identifying changes in molecular markers associated with the localization of cells. We propose correction strategies that reduce artefact-induced relationships.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>SpatioMark is implemented in the Statial R package on Bioconductor: https:\/\/bioconductor.org\/packages\/release\/bioc\/html\/Statial.html.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaf409","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T10:03:28Z","timestamp":1752746608000},"source":"Crossref","is-referenced-by-count":0,"title":["SpatioMark: quantifying the impact of spatial proximity on cell phenotype"],"prefix":"10.1093","volume":"41","author":[{"given":"Sourish S","family":"Iyengar","sequence":"first","affiliation":[{"name":"Centre for Cancer Research, Westmead Institute for Medical Research, The University of Sydney , Westmead, NSW 2145,","place":["Australia"]},{"name":"Sydney Precision Data Science Centre, The University of Sydney , Sydney, NSW 2006,","place":["Australia"]},{"name":"School of Mathematics and Statistics, The University of Sydney , Sydney, NSW 2006,","place":["Australia"]}]},{"given":"Alex R","family":"Qin","sequence":"additional","affiliation":[{"name":"Centre for Cancer Research, Westmead Institute for Medical Research, The University of Sydney , Westmead, NSW 2145,","place":["Australia"]},{"name":"Sydney Precision Data Science Centre, The University of Sydney , Sydney, NSW 2006,","place":["Australia"]},{"name":"School of Mathematics and Statistics, The University of Sydney , Sydney, NSW 2006,","place":["Australia"]}]},{"given":"Nicholas","family":"Robertson","sequence":"additional","affiliation":[{"name":"Sydney Precision Data Science Centre, The University of Sydney , Sydney, NSW 2006,","place":["Australia"]},{"name":"School of Mathematics and Statistics, The University of Sydney , Sydney, NSW 2006,","place":["Australia"]}]},{"given":"Andrew N","family":"Harman","sequence":"additional","affiliation":[{"name":"Centre for Cancer Research, Westmead Institute for Medical Research, The University of Sydney , Westmead, NSW 2145,","place":["Australia"]},{"name":"School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney , Sydney, NSW 2006,","place":["Australia"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5253-4747","authenticated-orcid":false,"given":"Ellis","family":"Patrick","sequence":"additional","affiliation":[{"name":"Centre for Cancer Research, Westmead Institute for Medical Research, The University of Sydney , Westmead, NSW 2145,","place":["Australia"]},{"name":"Sydney Precision Data Science Centre, The University of Sydney , Sydney, NSW 2006,","place":["Australia"]},{"name":"School of Mathematics and Statistics, The University of Sydney , Sydney, NSW 2006,","place":["Australia"]}]}],"member":"286","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"2025081319172234100_btaf409-B1","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/s41576-020-00292-x","article-title":"Deciphering cell\u2013cell interactions and communication from gene expression","volume":"22","author":"Armingol","year":"2021","journal-title":"Nat Rev Genet"},{"key":"2025081319172234100_btaf409-B2","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.celrep.2019.08.077","article-title":"Modeling cell-cell interactions from spatial molecular data with spatial variance component analysis","volume":"29","author":"Arnol","year":"2019","journal-title":"Cell Rep"},{"key":"2025081319172234100_btaf409-B3","doi-asserted-by":"crossref","first-page":"652631","DOI":"10.3389\/fimmu.2021.652631","article-title":"Adjacent cell marker lateral spillover compensation and reinforcement for multiplexed images","volume":"12","author":"Bai","year":"2021","journal-title":"Front Immunol"},{"key":"2025081319172234100_btaf409-B4","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.3390\/molecules26071905","article-title":"Na+\/K+-ATPase revisited: on its mechanism of action, role in cancer, and activity modulation","volume":"26","author":"Bej\u010dek","year":"2021","journal-title":"Molecules"},{"key":"2025081319172234100_btaf409-B5","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1038\/s41592-019-0582-9","article-title":"ilastik: interactive machine learning for (bio)image analysis","volume":"16","author":"Berg","year":"2019","journal-title":"Nat Methods"},{"key":"2025081319172234100_btaf409-B6","doi-asserted-by":"publisher","first-page":"3099","DOI":"10.1093\/bioinformatics\/btac268","article-title":"spicyR: spatial analysis of in situ cytometry data in R","volume":"38","author":"Canete","year":"2022","journal-title":"Bioinformatics"},{"key":"2025081319172234100_btaf409-B7","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1038\/s41592-022-01728-4","article-title":"Screening cell\u2013cell communication in spatial transcriptomics via collective optimal transport","volume":"20","author":"Cang","year":"2023","journal-title":"Nat Methods"},{"key":"2025081319172234100_btaf409-B8","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s13059-021-02286-2","article-title":"Giotto: a toolbox for integrative analysis and visualization of spatial expression data","volume":"22","author":"Dries","year":"2021","journal-title":"Genome Biol"},{"key":"2025081319172234100_btaf409-B9","doi-asserted-by":"publisher","first-page":"2352","DOI":"10.1089\/ars.2012.4834","article-title":"CD163 and inflammation: biological, diagnostic, and therapeutic aspects","volume":"18","author":"Etzerodt","year":"2013","journal-title":"Antioxid Redox Signal"},{"key":"2025081319172234100_btaf409-B10","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/s41467-023-44560-w","article-title":"BIDCell: biologically-informed self-supervised learning for segmentation of subcellular spatial transcriptomics data","volume":"15","author":"Fu","year":"2024","journal-title":"Nat Commun"},{"key":"2025081319172234100_btaf409-B11","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1016\/j.cell.2018.08.039","article-title":"A structured tumor-immune microenvironment in triple negative breast cancer revealed by multiplexed ion beam imaging","volume":"174","author":"Keren","year":"2018","journal-title":"Cell"},{"key":"2025081319172234100_btaf409-B12","doi-asserted-by":"publisher","first-page":"e0193779","DOI":"10.1371\/journal.pone.0193779","article-title":"Na+\/K+ ATPase activity promotes invasion of endocrine resistant breast cancer cells","volume":"13","author":"Khajah","year":"2018","journal-title":"PLoS One"},{"key":"2025081319172234100_btaf409-B13","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1038\/s41592-021-01203-6","article-title":"Spatial omics and multiplexed imaging to explore cancer biology","volume":"18","author":"Lewis","year":"2021","journal-title":"Nat Methods"},{"key":"2025081319172234100_btaf409-B14","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s13059-023-03159-6","article-title":"Niche-DE: niche-differential gene expression analysis in spatial transcriptomics data identifies context-dependent cell\u2013cell interactions","volume":"25","author":"Mason","year":"2024","journal-title":"Genome Biol"},{"key":"2025081319172234100_btaf409-B15","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1002\/cyto.a.24729","article-title":"Spatial analysis for highly multiplexed imaging data to identify tissue microenvironments","volume":"103","author":"Patrick","year":"2023","journal-title":"Cytometry A"},{"key":"2025081319172234100_btaf409-B16","doi-asserted-by":"publisher","first-page":"2083","DOI":"10.1158\/1535-7163.MCT-11-0421","article-title":"Digitoxin-induced cytotoxicity in cancer cells is mediated through distinct kinase and interferon signaling networks","volume":"10","author":"Prassas","year":"2011","journal-title":"Mol Cancer Ther"},{"key":"2025081319172234100_btaf409-B17","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1016\/j.cell.2020.07.005","article-title":"Coordinated cellular neighborhoods orchestrate antitumoral immunity at the colorectal cancer invasive front","volume":"182","author":"Sch\u00fcrch","year":"2020","journal-title":"Cell"},{"key":"2025081319172234100_btaf409-B18","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/s12307-014-0145-7","article-title":"Macrophage infiltration in tumor stroma is related to tumor cell expression of CD163 in colorectal cancer","volume":"7","author":"Shabo","year":"2014","journal-title":"Cancer Microenviron"},{"key":"2025081319172234100_btaf409-B19","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.1093\/bioinformatics\/btv066","article-title":"ClassifyR: an R package for performance assessment of classification with applications to transcriptomics","volume":"31","author":"Strbenac","year":"2015","journal-title":"Bioinformatics"},{"key":"2025081319172234100_btaf409-B20","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/s13059-022-02663-5","article-title":"Explainable multiview framework for dissecting spatial relationships from highly multiplexed data","volume":"23","author":"Tanevski","year":"2022","journal-title":"Genome Biol"},{"key":"2025081319172234100_btaf409-B22","doi-asserted-by":"publisher","first-page":"17","DOI":"10.18637\/jss.v077.i01","article-title":"ranger: a fast implementation of random forests for high dimensional data in C++ and R","volume":"77","author":"Wright","year":"2017","journal-title":"J Stat Soft"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btaf409\/63790748\/btaf409.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/41\/8\/btaf409\/63790748\/btaf409.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/41\/8\/btaf409\/63790748\/btaf409.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T23:17:30Z","timestamp":1755127050000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btaf409\/8205670"}},"subtitle":[],"editor":[{"given":"Janet","family":"Kelso","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2025,7,17]]},"references-count":21,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8,2]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btaf409","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.12.04.626887","asserted-by":"object"}]},"ISSN":["1367-4811"],"issn-type":[{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,8]]},"published":{"date-parts":[[2025,7,17]]},"article-number":"btaf409"}}