{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T12:27:42Z","timestamp":1779107262065,"version":"3.51.4"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Quantifying variability in protein expression is a major goal of systems biology and cell-to-cell variability in subcellular localization pattern has not been systematically quantified.<\/jats:p><jats:p>Results: We define a local measure to quantify cell-to-cell variability in high-throughput microscope images and show that it allows comparable measures of variability for proteins with diverse subcellular localizations. We systematically estimate cell-to-cell variability in the yeast GFP collection and identify examples of proteins that show cell-to-cell variability in their subcellular localization.<\/jats:p><jats:p>Conclusions: Automated image analysis methods can be used to quantify cell-to-cell variability in microscope images.<\/jats:p><jats:p>Contact: \u00a0alan.moses@utoronto.ca<\/jats:p><jats:p>Availability and Implementation: Software and data are available at http:\/\/www.moseslab.csb.utoronto.ca\/louis-f\/<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btu759","type":"journal-article","created":{"date-parts":[[2014,11,15]],"date-time":"2014-11-15T04:10:48Z","timestamp":1416024648000},"page":"940-947","source":"Crossref","is-referenced-by-count":16,"title":["Local statistics allow quantification of cell-to-cell variability from high-throughput microscope images"],"prefix":"10.1093","volume":"31","author":[{"given":"Louis-Fran\u00e7ois","family":"Handfield","sequence":"first","affiliation":[{"name":"1 Department of Computer Science, 2Department of Cell & Systems Biology and 3Department of Molecular Genetics, University of Toronto, Ontario M5S 3B2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bob","family":"Strome","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science, 2Department of Cell & Systems Biology and 3Department of Molecular Genetics, University of Toronto, Ontario M5S 3B2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yolanda T.","family":"Chong","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science, 2Department of Cell & Systems Biology and 3Department of Molecular Genetics, University of Toronto, Ontario M5S 3B2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan M.","family":"Moses","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science, 2Department of Cell & Systems Biology and 3Department of Molecular Genetics, University of Toronto, Ontario M5S 3B2, Canada"},{"name":"1 Department of Computer Science, 2Department of Cell & Systems Biology and 3Department of Molecular Genetics, University of Toronto, Ontario M5S 3B2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,12,9]]},"reference":[{"key":"2023020116192428000_btu759-B1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1080\/00031305.1992.10475879","article-title":"An introduction to kernel and nearest-neighbor nonparametric regression","volume":"46","author":"Altman","year":"1992","journal-title":"Am. Stat."},{"key":"2023020116192428000_btu759-B2","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1093\/biomet\/77.4.669","article-title":"Identification of nonlinear time series: first order characterization and order determination","volume":"77","author":"Auestad","year":"1990","journal-title":"Biometrika"},{"key":"2023020116192428000_btu759-B3","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/ng1807","article-title":"Noise in protein expression scales with natural protein abundance","volume":"38","author":"Bar-Even","year":"2006","journal-title":"Nat. Genet."},{"key":"2023020116192428000_btu759-B4","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1080\/00401706.1977.10489521","article-title":"Variable kernel estimates of multivariate densities","volume":"19","author":"Breiman","year":"1977","journal-title":"Technometrics"},{"key":"2023020116192428000_btu759-B5","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/nature07292","article-title":"Frequency-modulated nuclear localization bursts coordinate gene regulation","volume":"455","author":"Cai","year":"2008","journal-title":"Nature"},{"key":"2023020116192428000_btu759-B6","first-page":"1183","article-title":"Stochastic gene expression in a single cell","volume":"297","author":"Elowitz","year":"2002","journal-title":"Sci. Signal."},{"key":"2023020116192428000_btu759-B7","doi-asserted-by":"crossref","first-page":"e1003085","DOI":"10.1371\/journal.pcbi.1003085","article-title":"Unsupervised clustering of subcellular protein expression patterns in high-throughput microscopy images reveals protein complexes and functional relationships between proteins","volume":"9","author":"Handfield","year":"2013","journal-title":"PLoS Comput. Biol."},{"key":"2023020116192428000_btu759-B8","doi-asserted-by":"crossref","DOI":"10.1017\/CCOL0521382483","volume-title":"Applied Nonparametric Regression","author":"Hardle","year":"1990"},{"key":"2023020116192428000_btu759-B9","first-page":"120","article-title":"Local regression: automatic kernel carpentry","volume":"8","author":"Hastie","year":"1993","journal-title":"Stat. Sci."},{"key":"2023020116192428000_btu759-B10","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/nature02026","article-title":"Global analysis of protein localization in budding yeast","volume":"425","author":"Huh","year":"2003","journal-title":"Nature"},{"key":"2023020116192428000_btu759-B11","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1083\/jcb.200303030","article-title":"Oscillatory nucleocytoplasmic shuttling of the general stress response transcriptional activators msn2 and msn4 in Saccharomyces cerevisiae","volume":"161","author":"Jacquet","year":"2003","journal-title":"J. Cell Biol."},{"key":"2023020116192428000_btu759-B12","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1126\/science.1239999","article-title":"Functional roles of pulsing in genetic circuits","volume":"342","author":"Levine","year":"2013","journal-title":"Science"},{"key":"2023020116192428000_btu759-B13","doi-asserted-by":"crossref","first-page":"e264","DOI":"10.1371\/journal.pbio.0060264","article-title":"Network hubs buffer environmental variation in Saccharomyces cerevisiae","volume":"6","author":"Levy","year":"2008","journal-title":"PLoS Biol."},{"key":"2023020116192428000_btu759-B14","doi-asserted-by":"crossref","first-page":"10472","DOI":"10.1073\/pnas.0914302107","article-title":"Exploiting the determinants of stochastic gene expression in Saccharomyces cerevisiae for genome-wide prediction of expression noise","volume":"107","author":"Li","year":"2010","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023020116192428000_btu759-B15","doi-asserted-by":"crossref","first-page":"e1003504","DOI":"10.1371\/journal.pcbi.1003504","article-title":"Quantitative protein localization signatures reveal an association between spatial and functional divergences of proteins","volume":"10","author":"Loo","year":"2014","journal-title":"PLoS Comput. Biol."},{"key":"2023020116192428000_btu759-B16","doi-asserted-by":"crossref","first-page":"10147","DOI":"10.1073\/pnas.0812771106","article-title":"Widespread reorganization of metabolic enzymes into reversible assemblies upon nutrient starvation","volume":"106","author":"Narayanaswamy","year":"2009","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023020116192428000_btu759-B17","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1038\/nature04785","article-title":"Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise","volume":"441","author":"Newman","year":"2006","journal-title":"Nature"},{"key":"2023020116192428000_btu759-B18","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0960-9822(00)00337-7","article-title":"Clb\/cdc28 kinases promote nuclear export of the replication initiator proteins mcm2\u20137","volume":"10","author":"Nguyen","year":"2000","journal-title":"Curr. Biol."},{"key":"2023020116192428000_btu759-B19","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s004380051084","article-title":"Regulated nuclear localisation of the yeast transcription factor ace2p controls expression of chitinase (cts1) in Saccharomyces cerevisiae","volume":"262","author":"O\u2019Conall\u00e1in","year":"1999","journal-title":"Mol. Gen. Genet."},{"key":"2023020116192428000_btu759-B20","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1083\/jcb.142.3.613","article-title":"The sorting of mitochondrial DNA and mitochondrial proteins in zygotes: preferential transmission of mitochondrial DNA to the medial bud","volume":"142","author":"Okamoto","year":"1998","journal-title":"J. Cell Biol."},{"key":"2023020116192428000_btu759-B21","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1126\/science.1222161","article-title":"Using cell-to-cell variability a new era in molecular biology","volume":"336","author":"Pelkmans","year":"2012","journal-title":"Science"},{"key":"2023020116192428000_btu759-B22","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1186\/1471-2105-11-263","article-title":"The yeast resource center public image repository: a large database of fluorescence microscopy images","volume":"11","author":"Riffle","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"2023020116192428000_btu759-B23","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0169-7161(04)24009-3","article-title":"Multi-dimensional density estimation","volume":"24","author":"Scott","year":"2004","journal-title":"Handbook Stat."},{"key":"2023020116192428000_btu759-B24","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4612-4026-6","volume-title":"Smoothing Methods in Statistics","author":"Simonoff","year":"1996"},{"key":"2023020116192428000_btu759-B25","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/nrm3044","article-title":"Origins of regulated cell-to-cell variability","volume":"12","author":"Snijder","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2023020116192428000_btu759-B26","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.cub.2009.02.024","article-title":"Regulation of spo12 phosphorylation and its essential role in the fear network","volume":"19","author":"Tomson","year":"2009","journal-title":"Curr. Biol."},{"key":"2023020116192428000_btu759-B27","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/19775","article-title":"Cfi1 prevents premature exit from mitosis by anchoring cdc14 phosphatase in the nucleolus","volume":"398","author":"Visintin","year":"1999","journal-title":"Nature"},{"key":"2023020116192428000_btu759-B28","doi-asserted-by":"crossref","first-page":"6628","DOI":"10.1073\/pnas.1131932100","article-title":"Subcellular localization of yeast ribonucleotide reductase regulated by the DNA replication and damage checkpoint pathways","volume":"100","author":"Yao","year":"2003","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023020116192428000_btu759-B29","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/1752-0509-7-54","article-title":"Single-cell phenomics reveals intra-species variation of phenotypic noise in yeast","volume":"7","author":"Yvert","year":"2013","journal-title":"BMC Syst. Biol."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/31\/6\/940\/49011830\/bioinformatics_31_6_940.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/31\/6\/940\/49011830\/bioinformatics_31_6_940.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T02:16:01Z","timestamp":1717553761000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/31\/6\/940\/215564"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12,9]]},"references-count":29,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,3,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btu759","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2015,3,15]]},"published":{"date-parts":[[2014,12,9]]}}}