{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T21:04:04Z","timestamp":1767906244842,"version":"3.49.0"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"23","license":[{"start":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T00:00:00Z","timestamp":1635984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005567","name":"H. Lee Moffitt Cancer Center & Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005567","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NCI designated Comprehensive Cancer Center","award":["P30-CA076292"],"award-info":[{"award-number":["P30-CA076292"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Summary<\/jats:title>\n                  <jats:p>Multiplex immunofluorescence (mIF) staining combined with quantitative digital image analysis is a novel and increasingly used technique that allows for the characterization of the tumor immune microenvironment (TIME). Generally, mIF data is used to examine the abundance of immune cells in the TIME; however, this does not capture spatial patterns of immune cells throughout the TIME, a metric increasingly recognized as important for prognosis. To address this gap, we developed an R package spatialTIME that enables spatial analysis of mIF data, as well as the iTIME web application that provides a robust but simplified user interface for describing both abundance and spatial architecture of the TIME. The spatialTIME package calculates univariate and bivariate spatial statistics (e.g. Ripley\u2019s K, Besag\u2019s L, Macron\u2019s M and G or nearest neighbor distance) and creates publication quality plots for spatial organization of the cells in each tissue sample. The iTIME web application allows users to statistically compare the abundance measures with patient clinical features along with visualization of the TIME for one tissue sample at a time.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>spatialTIME is implemented in R and can be downloaded from GitHub (https:\/\/github.com\/FridleyLab\/spatialTIME) or CRAN. An extensive vignette for using spatialTIME can also be found at https:\/\/cran.r-project.org\/web\/packages\/spatialTIME\/index.html. iTIME is implemented within a R Shiny application and can be accessed online (http:\/\/itime.moffitt.org\/), with code available on GitHub (https:\/\/github.com\/FridleyLab\/iTIME).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btab757","type":"journal-article","created":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T19:12:04Z","timestamp":1635534724000},"page":"4584-4586","source":"Crossref","is-referenced-by-count":27,"title":["spatialTIME and iTIME: R package and Shiny application for visualization and analysis of immunofluorescence data"],"prefix":"10.1093","volume":"37","author":[{"given":"Jordan H","family":"Creed","sequence":"first","affiliation":[{"name":"Department of Biostatistics and Bioinformatics , Tampa, FL, USA"}]},{"given":"Christopher M","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics , Tampa, FL, USA"}]},{"given":"Alex C","family":"Soupir","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics , Tampa, FL, USA"},{"name":"Department of Tumor Biology , Tampa, FL, USA"}]},{"given":"Christelle M","family":"Colin-Leitzinger","sequence":"additional","affiliation":[{"name":"Department of Cancer Epidemiology , Tampa, FL, USA"}]},{"given":"Gregory J","family":"Kimmel","sequence":"additional","affiliation":[{"name":"Department of Integrated Mathematical Oncology , Tampa, FL, USA"}]},{"given":"Oscar E","family":"Ospina","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics , Tampa, FL, USA"}]},{"given":"Nicholas H","family":"Chakiryan","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Oncology , Tampa, FL, USA"}]},{"given":"Joseph","family":"Markowitz","sequence":"additional","affiliation":[{"name":"Department of Cutaneous Oncology, Moffitt Cancer Center , Tampa, FL 33612, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6620-8600","authenticated-orcid":false,"given":"Lauren C","family":"Peres","sequence":"additional","affiliation":[{"name":"Department of Cancer Epidemiology , Tampa, FL, USA"}]},{"given":"Anna","family":"Coghill","sequence":"additional","affiliation":[{"name":"Department of Cancer Epidemiology , Tampa, FL, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7739-7956","authenticated-orcid":false,"given":"Brooke L","family":"Fridley","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics , Tampa, FL, USA"}]}],"member":"286","published-online":{"date-parts":[[2021,11,4]]},"reference":[{"key":"2023061310542682400_btab757-B1","doi-asserted-by":"crossref","first-page":"e94137","DOI":"10.1371\/journal.pone.0094137","article-title":"A systematic comparison of supervised classifiers","volume":"9","author":"Amancio","year":"2014","journal-title":"PLoS One"},{"key":"2023061310542682400_btab757-B2","volume-title":"Spatial Point Patterns: Methodology and Applications with R","author":"Baddeley","year":"2016"},{"key":"2023061310542682400_btab757-B3","first-page":"193","article-title":"Comments on Ripley's paper","volume":"B39","author":"Besag","year":"1977","journal-title":"J. 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