{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T04:58:29Z","timestamp":1772773109973,"version":"3.50.1"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2016,12,16]],"date-time":"2016-12-16T00:00:00Z","timestamp":1481846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/about_us\/legal\/notices"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"crossref","award":["OPP1061177"],"award-info":[{"award-number":["OPP1061177"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH BTP training","award":["T32-GM008449-23"],"award-info":[{"award-number":["T32-GM008449-23"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>High throughput screening by fluorescence activated cell sorting (FACS) is a common task in protein engineering and directed evolution. It can also be a rate-limiting step if high false positive or negative rates necessitate multiple rounds of enrichment. Current FACS software requires the user to define sorting gates by intuition and is practically limited to two dimensions. In cases when multiple rounds of enrichment are required, the software cannot forecast the enrichment effort required.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We have developed CellSort, a support vector machine (SVM) algorithm that identifies optimal sorting gates based on machine learning using positive and negative control populations. CellSort can take advantage of more than two dimensions to enhance the ability to distinguish between populations. We also present a Bayesian approach to predict the number of sorting rounds required to enrich a population from a given library size. This Bayesian approach allowed us to determine strategies for biasing the sorting gates in order to reduce the required number of enrichment rounds. This algorithm should be generally useful for improve sorting outcomes and reducing effort when using FACS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and Implementation<\/jats:title>\n                  <jats:p>Source code available at http:\/\/tyolab.northwestern.edu\/tools\/.<\/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\/btw710","type":"journal-article","created":{"date-parts":[[2016,11,8]],"date-time":"2016-11-08T20:07:04Z","timestamp":1478635624000},"page":"909-916","source":"Crossref","is-referenced-by-count":13,"title":["CellSort: a support vector machine tool for optimizing fluorescence-activated cell sorting and reducing experimental effort"],"prefix":"10.1093","volume":"33","author":[{"given":"Jessica S","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dante A","family":"Pertusi","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adebola V","family":"Adeniran","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith E J","family":"Tyo","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,12,16]]},"reference":[{"key":"2023020204514531700_btw710-B1","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. Genetics"},{"key":"2023020204514531700_btw710-B2","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1093\/emboj\/20.12.3167","article-title":"Cell signaling can direct either binary or graded transcriptional responses","volume":"20","author":"Biggar","year":"2001","journal-title":"EMBO J"},{"key":"2023020204514531700_btw710-B3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1145\/1961189.1961199","article-title":"LIBSVM: A library for support vector machines","volume":"2","author":"Chang","year":"2011","journal-title":"ACM Trans. Intell. Syst. Technol"},{"key":"2023020204514531700_btw710-B4","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ymeth.2012.03.009","article-title":"Directed evolution as a powerful synthetic biology tool","volume":"60","author":"Cobb","year":"2013","journal-title":"Methods"},{"key":"2023020204514531700_btw710-B5","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0022-1759(00)00236-2","article-title":"Flow cytometric screening of cell-based libraries","volume":"243","author":"Daugherty","year":"2000","journal-title":"J. Immunol. Methods"},{"key":"2023020204514531700_btw710-B6","volume-title":"Non-Radioactive Labelling: A Practical Introduction","author":"Garman","year":"1997"},{"key":"2023020204514531700_btw710-B7","volume-title":"Coding and Information Theory","author":"Hamming","year":"1986","edition":"2nd edn."},{"key":"2023020204514531700_btw710-B8","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1093\/clinchem\/48.10.1819","article-title":"The history and future of the fluorescence activated cell sorter and flow cytometry: a view from Stanford","volume":"48","author":"Herzenberg","year":"2002","journal-title":"Clin. Chem"},{"key":"2023020204514531700_btw710-B9","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1073\/pnas.69.7.1934","article-title":"Demonstration that antigen-binding cells are precursors of antibody-producing cells after purification with a fluorescence-activated cell sorter","volume":"69","author":"Julius","year":"1972","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"2023020204514531700_btw710-B10","doi-asserted-by":"crossref","first-page":"145.","DOI":"10.1186\/1471-2105-10-145","article-title":"flowClust: a Bioconductor package for automated gating of flow cytometry data","volume":"10","author":"Lo","year":"2009","journal-title":"BMC Bioinform"},{"key":"2023020204514531700_btw710-B11","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/0378-1119(95)00037-7","article-title":"Yeast vectors for the controlled expression of heterologous proteins in different genetic backgrounds","volume":"156","author":"Mumberg","year":"1995","journal-title":"Gene"},{"key":"2023020204514531700_btw710-B12","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1038\/nbt1206-1565","article-title":"What is a support vector machine?","volume":"24","author":"Noble","year":"2006","journal-title":"Nat. Biotechnol"},{"key":"2023020204514531700_btw710-B13","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrg3927","article-title":"Methods for the directed evolution of proteins","volume":"16","author":"Packer","year":"2015","journal-title":"Nat. Rev. Genet"},{"key":"2023020204514531700_btw710-B14","first-page":"2825","article-title":"Scikit-learn: Machine Learning in Python","volume":"12","author":"Pedregosa","year":"2011","journal-title":"J. Mach. Learn. Res"},{"key":"2023020204514531700_btw710-B15","doi-asserted-by":"crossref","first-page":"S69","DOI":"10.1002\/cyto.b.20554","article-title":"Elucidation of seventeen human peripheral blood B-cell subsets and quantification of the tetanus response using a density-based method for the automated identification of cell populations in multidimensional flow cytometry data","volume":"78B","author":"Qian","year":"2010","journal-title":"Cytometry B Clin. Cytometry"},{"key":"2023020204514531700_btw710-B16","volume-title":"Learning with Kernels: Support Vector Machines, Regularization, Optimization, and beyond. Adaptive Computation and Machine Learning","author":"Sch\u00f6lkopf","year":"2002"},{"key":"2023020204514531700_btw710-B17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2105-7-282","article-title":"Automated in-silico detection of cell populations in flow cytometry readouts and its application to leukemia disease monitoring","volume":"7","author":"Toedling","year":"2006","journal-title":"BMC Bioinform"},{"key":"2023020204514531700_btw710-B18","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1021\/bp990133s","article-title":"Fine affinity discrimination by yeast surface display and flow cytometry","volume":"16","author":"VanAntwerp","year":"2000","journal-title":"Biotechnol. Progress"},{"key":"2023020204514531700_btw710-B19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2015.00380","article-title":"An introduction to automated flow cytometry gating tools and their implementation","volume":"6","author":"Verschoor","year":"2015","journal-title":"Front. Immunol"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/33\/6\/909\/49038293\/bioinformatics_33_6_909.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/33\/6\/909\/49038293\/bioinformatics_33_6_909.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T04:55:05Z","timestamp":1675313705000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/33\/6\/909\/2725493"}},"subtitle":[],"editor":[{"given":"Jonathan","family":"Wren","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2016,12,16]]},"references-count":19,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,3,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btw710","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,3,15]]},"published":{"date-parts":[[2016,12,16]]}}}