{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:34:15Z","timestamp":1772138055323,"version":"3.50.1"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"21","license":[{"start":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T00:00:00Z","timestamp":1662336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1U54CA209988"],"award-info":[{"award-number":["1U54CA209988"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54-HG008100"],"award-info":[{"award-number":["U54-HG008100"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>High-throughput fluorescent microscopy is a popular class of techniques for studying tissues and cells through automated imaging and feature extraction of hundreds to thousands of samples. Like other high-throughput assays, these approaches can suffer from unwanted noise and technical artifacts that obscure the biological signal. In this work, we consider how an experimental design incorporating multiple levels of replication enables the removal of technical artifacts from such image-based platforms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We develop a general approach to remove technical artifacts from high-throughput image data that leverages an experimental design with multiple levels of replication. To illustrate the methods, we consider microenvironment microarrays (MEMAs), a high-throughput platform designed to study cellular responses to microenvironmental perturbations. In application to MEMAs, our approach removes unwanted spatial artifacts and thereby enhances the biological signal. This approach has broad applicability to diverse biological assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>Raw data are on synapse (syn2862345), analysis code is on github: gjhunt\/mema_norm, a reproducible Docker image is available on dockerhub: gjhunt\/mema_norm.<\/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\/btac606","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T16:05:14Z","timestamp":1662048314000},"page":"4934-4940","source":"Crossref","is-referenced-by-count":3,"title":["Systematic replication enables normalization of high-throughput imaging assays"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7794-8404","authenticated-orcid":false,"given":"Gregory J","family":"Hunt","sequence":"first","affiliation":[{"name":"Department of Mathematics, College of William & Mary , Williamsburg, VA 23185, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A","family":"Dane","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Knight Cancer Institute OHSU Center for Spatial Systems Biomedicine Oregon Health and Science University , Portland, OR 97201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James E","family":"Korkola","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Knight Cancer Institute OHSU Center for Spatial Systems Biomedicine Oregon Health and Science University , Portland, OR 97201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura M","family":"Heiser","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Knight Cancer Institute OHSU Center for Spatial Systems Biomedicine Oregon Health and Science University , Portland, OR 97201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johann A","family":"Gagnon-Bartsch","sequence":"additional","affiliation":[{"name":"Department of Statistics, University of Michigan , Ann Arbor, MI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,9,5]]},"reference":[{"key":"2022103112492526000_btac606-B1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13040-016-0088-2","article-title":"Robust normalization protocols for multiplexed fluorescence bioimage analysis","volume":"9","author":"Ahmed Raza","year":"2016","journal-title":"BioData Min"},{"key":"2022103112492526000_btac606-B2","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/978-1-4939-9773-2_23","article-title":"Multiplexed immunohistochemical consecutive staining on single slide (MICSSS): multiplexed chromogenic IHC assay for high-dimensional tissue analysis","volume":"2055","author":"Akturk","year":"2020","journal-title":"Methods Mol. 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