{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:34:28Z","timestamp":1772138068242,"version":"3.50.1"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["U10 CA180819"],"award-info":[{"award-number":["U10 CA180819"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Spatial proteomics can reveal the spatial organization of immune cells in the tumor immune microenvironment. Relating measures of spatial clustering, such as Ripley\u2019s K or Besag\u2019s L, to patient outcomes may offer important clinical insights. However, these measures require pre-specifying a radius in which to quantify clustering, yet no consensus exists on the optimal radius which may be context-specific.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We propose a SPatial Omnibus Test (SPOT) which conducts this analysis across a range of candidate radii. At each radius, SPOT evaluates the association between the spatial summary and outcome, adjusting for confounders. SPOT then aggregates results across radii using the Cauchy combination test, yielding an omnibus P-value characterizing the overall degree of association. Using simulations, we verify that the type I error rate is controlled and show SPOT can be more powerful than alternatives. We also apply SPOT to ovarian and lung cancer studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>An R package and tutorial are provided at https:\/\/github.com\/sarahsamorodnitsky\/SPOT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btae425","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T17:08:27Z","timestamp":1719594507000},"source":"Crossref","is-referenced-by-count":5,"title":["A Spatial Omnibus Test (SPOT) for Spatial Proteomic Data"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7909-0245","authenticated-orcid":false,"given":"Sarah","family":"Samorodnitsky","sequence":"first","affiliation":[{"name":"Public Health Sciences Division, Fred Hutchinson Cancer Center , Seattle 98109, USA"},{"name":"SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Center , Seattle 98109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6491-4432","authenticated-orcid":false,"given":"Katie","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology\/Oncology, University of California Los Angeles, Los Angeles 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoni","family":"Ribas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology\/Oncology, University of California Los Angeles, Los Angeles 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael C","family":"Wu","sequence":"additional","affiliation":[{"name":"Public Health Sciences Division, Fred Hutchinson Cancer Center , Seattle 98109, USA"},{"name":"SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Center , Seattle 98109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,7,1]]},"reference":[{"key":"2024071900144438200_btae425-B1","doi-asserted-by":"crossref","first-page":"e1002194","DOI":"10.1371\/journal.pmed.1002194","article-title":"Patterns of immune infiltration in breast cancer and their clinical implications: a gene-expression-based retrospective study","volume":"13","author":"Ali","year":"2016","journal-title":"PLoS Med"},{"key":"2024071900144438200_btae425-B2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v012.i06","volume":"12","author":"Baddeley","year":"2005","journal-title":"J Stat Softw"},{"key":"2024071900144438200_btae425-B3","doi-asserted-by":"crossref","DOI":"10.1201\/b19708","volume-title":"Spatial Point Patterns: Methodology and Applications with R","author":"Baddeley","year":"2015"},{"key":"2024071900144438200_btae425-B4","doi-asserted-by":"crossref","first-page":"1176935118782880","DOI":"10.1177\/1176935118782880","article-title":"A functional spatial analysis platform for discovery of immunological interactions predictive of low-grade to high-grade transition of pancreatic intraductal papillary mucinous neoplasms","volume":"17","author":"Barua","year":"2018","journal-title":"Cancer Inform"},{"key":"2024071900144438200_btae425-B5","first-page":"327","article-title":"Simple Monte Carlo tests for spatial pattern","volume":"26","author":"Besag","year":"1977","journal-title":"J Roy Stat Soc Ser C: Appl Stat"},{"key":"2024071900144438200_btae425-B6","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.immuni.2013.10.003","article-title":"Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer","volume":"39","author":"Bindea","year":"2013","journal-title":"Immunity"},{"key":"2024071900144438200_btae425-B7","doi-asserted-by":"crossref","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":"2024071900144438200_btae425-B8","doi-asserted-by":"crossref","first-page":"4584","DOI":"10.1093\/bioinformatics\/btab757","article-title":"spatialTIME and iTIME: R package and shiny application for visualization and analysis of immunofluorescence data","volume":"37","author":"Creed","year":"2021","journal-title":"Bioinformatics"},{"key":"2024071900144438200_btae425-B9","doi-asserted-by":"crossref","first-page":"i140","DOI":"10.1093\/bioinformatics\/btad245","article-title":"Deriving spatial features from in situ proteomics imaging to enhance cancer survival analysis","volume":"39","author":"Dayao","year":"2023","journal-title":"Bioinformatics"},{"key":"2024071900144438200_btae425-B10","volume-title":"Ripley\u2019s K Function","author":"Dixon","year":"2002"},{"key":"2024071900144438200_btae425-B11","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.ccell.2023.01.010","article-title":"Spatial profiling technologies illuminate the tumor microenvironment","volume":"41","author":"Elhanani","year":"2023","journal-title":"Cancer Cell"},{"key":"2024071900144438200_btae425-B12","doi-asserted-by":"crossref","volume-title":"Statistical Analysis and Modelling of Spatial Point Patterns","author":"Illian","DOI":"10.1002\/9780470725160"},{"key":"2024071900144438200_btae425-B13","doi-asserted-by":"crossref","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":"2024071900144438200_btae425-B14","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1080\/01621459.2018.1554485","article-title":"Cauchy combination test: a powerful test with analytic p-value calculation under arbitrary dependency structures","volume":"115","author":"Liu","year":"2020","journal-title":"J Am Stat Assoc"},{"key":"2024071900144438200_btae425-B15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/619281","article-title":"Characterizing the relative spatial structure of point patterns","volume":"2012","author":"Marcon","year":"2012","journal-title":"Int J Ecol"},{"key":"2024071900144438200_btae425-B16","doi-asserted-by":"crossref","first-page":"100879","DOI":"10.1016\/j.patter.2023.100879","article-title":"Dimple: an R package to quantify, visualize, and model spatial cellular interactions from multiplex imaging with distance matrices","volume":"4","author":"Masotti","year":"2023","journal-title":"Patterns"},{"key":"2024071900144438200_btae425-B17","doi-asserted-by":"crossref","first-page":"255","DOI":"10.2307\/3212829","article-title":"The second-order analysis of stationary point processes","volume":"13","author":"Ripley","year":"1976","journal-title":"J Appl Probab"},{"key":"2024071900144438200_btae425-B18","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1021\/acs.jproteome.3c00462","volume":"23","author":"Seal","year":"2024","journal-title":"J Proteome Res"},{"key":"2024071900144438200_btae425-B19","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1093\/intimm\/dxw014","article-title":"Mechanisms of tumor escape in the context of the t-cell-inflamed and the non-t-cell-inflamed tumor microenvironment","volume":"28","author":"Spranger","year":"2016","journal-title":"Int Immunol"},{"key":"2024071900144438200_btae425-B20","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1158\/1541-7786.MCR-21-0411","article-title":"The spatial context of tumor-infiltrating immune cells associates with improved ovarian cancer survival","volume":"19","author":"Steinhart","year":"2021","journal-title":"Mol Cancer Res"},{"key":"2024071900144438200_btae425-B21","doi-asserted-by":"crossref","first-page":"e1009486","DOI":"10.1371\/journal.pcbi.1009486","article-title":"SPF: a spatial and functional data analytic approach to cell imaging data","volume":"18","author":"Vu","year":"2022","journal-title":"PLoS Comput Biol"},{"key":"2024071900144438200_btae425-B22","doi-asserted-by":"crossref","first-page":"e1011490","DOI":"10.1371\/journal.pcbi.1011490","article-title":"FunSpace: a functional and spatial analytic approach to cell imaging data using entropy measures","volume":"19","author":"Vu","year":"2023","journal-title":"PLoS Comput Biol"},{"key":"2024071900144438200_btae425-B23","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.3390\/cancers13123031","article-title":"Challenges and opportunities in the statistical analysis of multiplex immunofluorescence data","volume":"13","author":"Wilson","year":"2021","journal-title":"Cancers (Basel)"},{"key":"2024071900144438200_btae425-B24","author":"Wrobel","year":"2022"},{"key":"2024071900144438200_btae425-B25","author":"Wrobel","year":"2024"},{"key":"2024071900144438200_btae425-B26","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/978-1-0716-2986-4_8","volume-title":"Statistical Genomics","author":"Wrobel","year":"2023"},{"key":"2024071900144438200_btae425-B27","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1002\/gepi.21715","article-title":"Kernel machine SNP-set testing under multiple candidate kernels","volume":"37","author":"Wu","year":"2013","journal-title":"Genet Epidemiol"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btae425\/58382297\/btae425.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/40\/7\/btae425\/58591509\/btae425.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/40\/7\/btae425\/58591509\/btae425.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T20:15:00Z","timestamp":1721333700000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btae425\/7702328"}},"subtitle":[],"editor":[{"given":"Janet","family":"Kelso","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,7,1]]},"references-count":27,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btae425","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.03.08.584117","asserted-by":"object"}]},"ISSN":["1367-4811"],"issn-type":[{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,7]]},"published":{"date-parts":[[2024,7,1]]},"article-number":"btae425"}}