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These in situ methods are valuable in understanding cell\u2013cell interactions, but few standardized processing steps or normalization techniques of multiplexed imaging data are available.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We implement and compare data transformations and normalization algorithms in multiplexed imaging data. Our methods adapt the ComBat and functional data registration methods to remove slide effects in this domain, and we present an evaluation framework to compare the proposed approaches. We present clear slide-to-slide variation in the raw, unadjusted data and show that many of the proposed normalization methods reduce this variation while preserving and improving the biological signal. Furthermore, we find that dividing multiplexed imaging data by its slide mean, and the functional data registration methods, perform the best under our proposed evaluation framework. In summary, this approach provides a foundation for better data quality and evaluation criteria in multiplexed imaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>Source code is provided at: https:\/\/github.com\/statimagcoll\/MultiplexedNormalization and an R package to implement these methods is available here: https:\/\/github.com\/ColemanRHarris\/mxnorm.<\/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\/btab877","type":"journal-article","created":{"date-parts":[[2021,12,31]],"date-time":"2021-12-31T15:19:20Z","timestamp":1640963960000},"page":"1700-1707","source":"Crossref","is-referenced-by-count":33,"title":["Quantifying and correcting slide-to-slide variation in multiplexed immunofluorescence images"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6325-0694","authenticated-orcid":false,"given":"Coleman R","family":"Harris","sequence":"first","affiliation":[{"name":"Department of Biostatistics, Vanderbilt University Medical Center , Nashville, TN 37203, USA"}]},{"given":"Eliot T","family":"McKinley","sequence":"additional","affiliation":[{"name":"Epithelial Biology Center, Vanderbilt University Medical Center , Nashville, TN 37232, USA"},{"name":"Department of Cell and Developmental Biology, Vanderbilt University School of Medicine , Nashville, TN 37232, USA"}]},{"given":"Joseph T","family":"Roland","sequence":"additional","affiliation":[{"name":"Epithelial Biology Center, Vanderbilt University Medical Center , Nashville, TN 37232, USA"},{"name":"Department of Surgery, Vanderbilt University School of Medicine , Nashville, TN 37232, USA"}]},{"given":"Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Vanderbilt University Medical Center , Nashville, TN 37203, USA"},{"name":"Center for Quantitative Sciences, Vanderbilt University Medical Center , Nashville, TN 37232, USA"}]},{"given":"Martha J","family":"Shrubsole","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center , Nashville, TN 37232, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8438-0319","authenticated-orcid":false,"given":"Ken S","family":"Lau","sequence":"additional","affiliation":[{"name":"Epithelial Biology Center, Vanderbilt University Medical Center , Nashville, TN 37232, USA"},{"name":"Department of Cell and Developmental Biology, Vanderbilt University School of Medicine , Nashville, TN 37232, USA"}]},{"given":"Robert J","family":"Coffey","sequence":"additional","affiliation":[{"name":"Epithelial Biology Center, Vanderbilt University Medical Center , Nashville, TN 37232, USA"},{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN 37232, USA"}]},{"given":"Julia","family":"Wrobel","sequence":"additional","affiliation":[{"name":"Department of Biostatistics & Informatics, Colorado School of Public Health , Aurora, CO 80045, USA"}]},{"given":"Simon N","family":"Vandekar","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Vanderbilt University Medical Center , Nashville, TN 37203, USA"}]}],"member":"286","published-online":{"date-parts":[[2022,1,4]]},"reference":[{"key":"2023020108580481200_btab877-B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting linear mixed-effects models using lme4","volume":"67","author":"Bates","year":"2015","journal-title":"J. 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