{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T03:46:05Z","timestamp":1777693565226,"version":"3.51.4"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Automated identification of cell cycle phases captured via fluorescent microscopy is very important for understanding cell cycle and for drug discovery. In this article, we propose a novel cell detection method that utilizes both the intensity and shape information of the cell for better segmentation quality. In contrast to conventional off-line learning algorithms, an Online Support Vector Classifier (OSVC) is thus proposed, which removes support vectors from the old model and assigns new training examples weighted according to their importance to accommodate the ever-changing experimental conditions.<\/jats:p>\n               <jats:p>Results: We image three cell lines using fluorescent microscopy under different experiment conditions, including one treated with taxol. Then, we segment and classify the cell types into interphase, prophase, metaphase and anaphase. Experimental results show the effectiveness of the proposed system in image segmentation and cell phase identification.<\/jats:p>\n               <jats:p>Availability: The software and test datasets are available from the authors.<\/jats:p>\n               <jats:p>Contact: \u00a0zhou@crystal.harvard.edu<\/jats:p>\n               <jats:p>Supplementary information: Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btm530","type":"journal-article","created":{"date-parts":[[2007,11,8]],"date-time":"2007-11-08T01:26:33Z","timestamp":1194485193000},"page":"94-101","source":"Crossref","is-referenced-by-count":116,"title":["Novel cell segmentation and online SVM for cell cycle phase identification in automated microscopy"],"prefix":"10.1093","volume":"24","author":[{"given":"Meng","family":"Wang","sequence":"first","affiliation":[{"name":"1 Center for Bioinformatics, Harvard Center for Neurodegeneration and Repair, Harvard Medical School, 3rd floor, 1249 Boylston, Boston, MA 02215, 2Functional and Molecular Imaging Center, Department of Radiology, Brigham and Women's Hospital, One Brigham Circle, 1620 Tremont Street, Boston, MA 02121 and 3Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaobo","family":"Zhou","sequence":"additional","affiliation":[{"name":"1 Center for Bioinformatics, Harvard Center for Neurodegeneration and Repair, Harvard Medical School, 3rd floor, 1249 Boylston, Boston, MA 02215, 2Functional and Molecular Imaging Center, Department of Radiology, Brigham and Women's Hospital, One Brigham Circle, 1620 Tremont Street, Boston, MA 02121 and 3Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA"},{"name":"1 Center for Bioinformatics, Harvard Center for Neurodegeneration and Repair, Harvard Medical School, 3rd floor, 1249 Boylston, Boston, MA 02215, 2Functional and Molecular Imaging Center, Department of Radiology, Brigham and Women's Hospital, One Brigham Circle, 1620 Tremont Street, Boston, MA 02121 and 3Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuhai","family":"Li","sequence":"additional","affiliation":[{"name":"1 Center for Bioinformatics, Harvard Center for Neurodegeneration and Repair, Harvard Medical School, 3rd floor, 1249 Boylston, Boston, MA 02215, 2Functional and Molecular Imaging Center, Department of Radiology, Brigham and Women's Hospital, One Brigham Circle, 1620 Tremont Street, Boston, MA 02121 and 3Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy","family":"Huckins","sequence":"additional","affiliation":[{"name":"1 Center for Bioinformatics, Harvard Center for Neurodegeneration and Repair, Harvard Medical School, 3rd floor, 1249 Boylston, Boston, MA 02215, 2Functional and Molecular Imaging Center, Department of Radiology, Brigham and Women's Hospital, One Brigham Circle, 1620 Tremont Street, Boston, MA 02121 and 3Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randall W.","family":"King","sequence":"additional","affiliation":[{"name":"1 Center for Bioinformatics, Harvard Center for Neurodegeneration and Repair, Harvard Medical School, 3rd floor, 1249 Boylston, Boston, MA 02215, 2Functional and Molecular Imaging Center, Department of Radiology, Brigham and Women's Hospital, One Brigham Circle, 1620 Tremont Street, Boston, MA 02121 and 3Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen T.C.","family":"Wong","sequence":"additional","affiliation":[{"name":"1 Center for Bioinformatics, Harvard Center for Neurodegeneration and Repair, Harvard Medical School, 3rd floor, 1249 Boylston, Boston, MA 02215, 2Functional and Molecular Imaging Center, Department of Radiology, Brigham and Women's Hospital, One Brigham Circle, 1620 Tremont Street, Boston, MA 02121 and 3Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA"},{"name":"1 Center for Bioinformatics, Harvard Center for Neurodegeneration and Repair, Harvard Medical School, 3rd floor, 1249 Boylston, Boston, MA 02215, 2Functional and Molecular Imaging Center, Department of Radiology, Brigham and Women's Hospital, One Brigham Circle, 1620 Tremont Street, Boston, MA 02121 and 3Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2007,11,7]]},"reference":[{"key":"2023020209470508000_B1","first-page":"423","article-title":"Inhibitors of the G2 DNA damage checkpoint and their potential for cancer therapy","volume":"5","author":"Anderson","year":"2003","journal-title":"Prog. Cell Cycle Res"},{"key":"2023020209470508000_B2","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.ejca.2003.12.019","article-title":"In vitro modeling of human tumour behaviour in drug discovery programmes","volume":"40","author":"Baguley","year":"2004","journal-title":"Eur. J. Cancer"},{"key":"2023020209470508000_B3","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1093\/bioinformatics\/17.12.1213","article-title":"A neural network classifier capable of recognizing the patterns of all major subcellular structures in fluorescence microscope image of HeLa cells","volume":"17","author":"Boland","year":"2001","journal-title":"Bioinformatics"},{"key":"2023020209470508000_B4","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1002\/(SICI)1097-0320(19981101)33:3<366::AID-CYTO12>3.0.CO;2-R","article-title":"Automated recognition of pattern characteristic of subcellular structures in fluorescence microscopy images","volume":"33","author":"Boland","year":"1998","journal-title":"Cytometry"},{"key":"2023020209470508000_B5","first-page":"1579","article-title":"Fast kernel classifiers with online and active learning","volume":"6","author":"Borders","year":"2005","journal-title":"J. Mach. Lean. Res"},{"key":"2023020209470508000_B6","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1109\/34.391389","article-title":"Linear time Euclidean distance transform algorithms","volume":"17","author":"Breu","year":"1995","journal-title":"IEEE Trans. Pattern Anal. Mach. Intell"},{"key":"2023020209470508000_B7","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1177\/1087057107300707","article-title":"A Support Vector Machine Classifier for recognizing mitotic subphases using high-content screening data","volume":"12","author":"Charles","year":"2007","journal-title":"J. Biomol. Screen"},{"key":"2023020209470508000_B8","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/1471-2105-7-90","article-title":"A graphical model approach to automated classification of protein subcellular location patterns in multi-cell images","volume":"7","author":"Chen","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"2023020209470508000_B9","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1109\/TBME.2006.870201","article-title":"Automated segmentation, classification, and tracking of cancer cell nuclei in time-lapse microscopy","volume":"53","author":"Chen","year":"2006","journal-title":"IEEE Trans. Biomed. Eng"},{"key":"2023020209470508000_B10","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/BF00994018","article-title":"Support vector networks","volume":"20","author":"Cortes","year":"1995","journal-title":"Mach. Learn"},{"key":"2023020209470508000_B11","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1158\/0008-5472.708.65.3","article-title":"P300 Modulates Nuclear Morphology in Prostate Cancer","volume":"65","author":"Debes","year":"2005","journal-title":"Cancer Res"},{"key":"2023020209470508000_B12","doi-asserted-by":"crossref","first-page":"362","DOI":"10.4161\/cc.1.6.257","article-title":"Therapeutic exploitation of checkpoint defects in cancer cells lacking p53 function","volume":"1","author":"Dixon","year":"2002","journal-title":"Cell Cycle"},{"key":"2023020209470508000_B13","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.cam.2005.09.009","article-title":"Efficient optimization of support vector machine learning parameters for unbalanced datasets","volume":"196","author":"Eitrich","year":"2006","journal-title":"J. Comput. Appl. Math."},{"key":"2023020209470508000_B14","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1023\/A:1007662407062","article-title":"Large margin classification using the perceptron algorithm","volume":"37","author":"Freund","year":"1999","journal-title":"Mach. Learn"},{"key":"2023020209470508000_B15","first-page":"661","article-title":"Mitotic cell recognition with hidden markov models","volume":"5367","author":"Gallardo","year":"2004","journal-title":"Med. Imaging SPIE"},{"key":"2023020209470508000_B16","first-page":"5","article-title":"utomatic capacity tuning of very large VC-dimension classifiers","volume-title":"Advances in Neural Information Processing Systems.","author":"Guyon"},{"key":"2023020209470508000_B17","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1023\/A:1012487302797","article-title":"Gene selection for cancer classification using support vector machines","volume":"46","author":"Guyon","year":"2002","journal-title":"Mach. Learn"},{"key":"2023020209470508000_B18","first-page":"610","article-title":"Textural features for image classification","volume":"3","author":"Haralick","year":"1973","journal-title":"IEEE Trans. SMC"},{"key":"2023020209470508000_B19","first-page":"840","article-title":"Automated analysis of the mitotic phases of human cells in 3D fluorescence microscopy image sequences","volume-title":"Proceedings of the MICCAI\u201906.","author":"Harder","year":"2006"},{"key":"2023020209470508000_B20","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1117\/12.477903","article-title":"Feature reduction for improved recognition of subcellular location patterns in fluorescence microscope image","volume":"4962","author":"Huang","year":"2003","journal-title":"Proc. SPIE"},{"key":"2023020209470508000_B21","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1109\/TSP.2004.830991","article-title":"Online learning with Kernels","volume":"52","author":"Kivinen","year":"2004","journal-title":"IEEE Trans. Signal Process"},{"key":"2023020209470508000_B22","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1016\/S0031-3203(03)00038-4","article-title":"Online training of support vector classifier","volume":"36","author":"Lau","year":"2003","journal-title":"Pattern Recognit"},{"key":"2023020209470508000_B23","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1007\/978-3-540-28633-2_32","article-title":"Feature selection for multi-class problems using support vector machines","volume":"3157","author":"Li","year":"2004","journal-title":"Lect. Notes Comput. Sci"},{"key":"2023020209470508000_B24","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/cyto.a.10079","article-title":"A hybrid 3-D watershed algorithm incorporating gradient cues and object models for automatic segmentation of nuclei in confocal image stacks","volume":"56","author":"Lin","year":"2003","journal-title":"Cytometry A"},{"key":"2023020209470508000_B25","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/cyto.a.10107","article-title":"Image analysis for automatic segmentation of cytoplasms and classification of Rac1 activation","volume":"57","author":"Lindblad","year":"2004","journal-title":"Cytometry A"},{"key":"2023020209470508000_B26","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1109\/34.531803","article-title":"Texture features for browsing and retrieval of image data","volume":"18","author":"Manjunath","year":"1996","journal-title":"IEEE Trans. PAMI (PAMI-Special issuer on Digital Libraries)"},{"key":"2023020209470508000_B27","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1023\/B:VLSI.0000003028.71666.44","article-title":"Robust numerical features for description and classification of subcellular location patterns in fluorescence microscope images","volume":"35","author":"Murphy","year":"2003","journal-title":"J. VLSI Signal Process"},{"key":"2023020209470508000_B28","first-page":"185","article-title":"Fast training of support vector machines using sequential minimal optimization","volume-title":"Advances in Kernel Methods-Support Vector Learning.","author":"Platt","year":"1999"},{"key":"2023020209470508000_B29","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1037\/h0042519","article-title":"The perceptron: a probability model for information storage and organization in the brain","volume":"6","author":"Rosenblatt","year":"1958","journal-title":"Psychol. Rev"},{"key":"2023020209470508000_B30","first-page":"423","article-title":"Online learning meets optimization in the dual","volume-title":"Proceedings of the 19th Annual Conference on Learning Theory.","author":"Shalev-Shwartz","year":"2006"},{"key":"2023020209470508000_B31","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1109\/34.659930","article-title":"An unbiased detector of curvilinear structures","volume":"20","author":"Steger","year":"1998","journal-title":"IEEE Trans. Pattern Anal"},{"key":"2023020209470508000_B32","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/nchembio749","article-title":"Small molecules that delay S phase suppress a zebrafish bmyb mutant","volume":"1","author":"Stern","year":"2005","journal-title":"Nat. Chem. Biol"},{"key":"2023020209470508000_B33","volume-title":"Statistical Learning Theory.","author":"Vapnik","year":"1998"},{"key":"2023020209470508000_B34","first-page":"774","article-title":"Pattern recognition using generalized portrait method","volume":"24","author":"Vapnik","year":"1963","journal-title":"Automat. Rem. Contr"},{"key":"2023020209470508000_B35","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1109\/34.87344","article-title":"Watersheds in digital spaces: an efficient algorithm based on immersion simulations","volume":"13","author":"Vincent","year":"1991","journal-title":"IEEE Trans. PAMI"},{"key":"2023020209470508000_B36","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1155\/2002\/821782","article-title":"Algorithms for cytoplasm segmentation of fluorescence labelled cells","volume":"24","author":"Wahlby","year":"2002","journal-title":"Anal. Cell Pathol"},{"key":"2023020209470508000_B37","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1093\/protein\/gzh061","article-title":"Weighted-support vector machines for predicting membrane protein types based on pseudo-amino acid composition","volume":"17","author":"Wang","year":"2005","journal-title":"Protein Eng. Des. Sel"},{"key":"2023020209470508000_B38","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1471-2105-8-32","article-title":"Context based mixture model for cell phase identification in automated fluorescence microscopy","volume":"8","author":"Wang","year":"2007","journal-title":"BMC Bioinformatics"},{"key":"2023020209470508000_B39","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1109\/83.661186","article-title":"Snakes, shapes, and gradient vector flow","volume":"7","author":"Xu","year":"1998","journal-title":"IEEE Trans. Image Process"},{"key":"2023020209470508000_B40","first-page":"1536","article-title":"An efficient system for optical microscopy cell image segmentation, tracking and cell phase identification","volume-title":"Proceedings of IEEE ICIP.","author":"Yan","year":"2006"},{"key":"2023020209470508000_B41","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1109\/MSP.2006.1628879","article-title":"Informatics challenges of high-throughput microscopy","volume":"23","author":"Zhou","year":"2006","journal-title":"IEEE Signal Process. Mag"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/24\/1\/94\/49044677\/bioinformatics_24_1_94.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/24\/1\/94\/49044677\/bioinformatics_24_1_94.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T10:22:38Z","timestamp":1675333358000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/24\/1\/94\/205039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,11,7]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,1,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btm530","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2008,1,1]]},"published":{"date-parts":[[2007,11,7]]}}}