{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T07:14:59Z","timestamp":1780730099658,"version":"3.54.1"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T00:00:00Z","timestamp":1560384000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T00:00:00Z","timestamp":1560384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM093123"],"award-info":[{"award-number":["R01GM093123"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM065546"],"award-info":[{"award-number":["R01GM065546"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008982","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DBI1759934"],"award-info":[{"award-number":["DBI1759934"]}],"id":[{"id":"10.13039\/501100008982","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008982","name":"National Science Foundation","doi-asserted-by":"publisher","award":["IIS1763246"],"award-info":[{"award-number":["IIS1763246"]}],"id":[{"id":"10.13039\/501100008982","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1186\/s12859-019-2926-y","type":"journal-article","created":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T10:47:14Z","timestamp":1560422834000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["AutoCryoPicker: an unsupervised learning approach for fully automated single particle picking in Cryo-EM images"],"prefix":"10.1186","volume":"20","author":[{"given":"Adil","family":"Al-Azzawi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anes","family":"Ouadou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Tanner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0305-2853","authenticated-orcid":false,"given":"Jianlin","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,6,13]]},"reference":[{"issue":"4","key":"2926_CR1","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.molcel.2015.02.019","volume":"58","author":"E Nogales","year":"2015","unstructured":"Nogales E, Scheres SH. Cryo-EM: a unique tool for the visualization of macromolecular complexity. Mol Cell. 2015;58(4):677\u201389.","journal-title":"Mol Cell"},{"issue":"7","key":"2926_CR2","doi-asserted-by":"publisher","first-page":"1698","DOI":"10.1016\/j.cell.2016.05.040","volume":"165","author":"A Merk","year":"2016","unstructured":"Merk A, Bartesaghi A, Banerjee S, Falconieri V, Rao P, Davis MI, Pragani R, Boxer MB, Earl LA, Milne JLS, Subramaniam S. Breaking Cryo-EM resolution barriers to facilitate drug discovery. Cell. 2016;165(7):1698\u2013707.","journal-title":"Cell"},{"key":"2926_CR3","doi-asserted-by":"crossref","unstructured":"Doerr, Allison. 2016. \u201cSingle-particle cryo-electron microscopy.\u201d Nat Methods 23. \n                    https:\/\/www.nature.com\/articles\/nmeth.3700?draft=collection\n                    \n                  .","DOI":"10.1038\/nmeth.3700"},{"issue":"7553","key":"2926_CR4","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1038\/nature14247","volume":"521","author":"J Jiang","year":"2015","unstructured":"Jiang J, Pentelute BL, Collier RJ, Zhou ZH. Atomic structure of anthrax protective antigen pore elucidates toxin translocation. Nature. 2015;521(7553):545\u20139.","journal-title":"Nature"},{"issue":"6239","key":"2926_CR5","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1126\/science.aab1576","volume":"348","author":"A Bartesaghi","year":"2015","unstructured":"Bartesaghi A, Merk A, Banerjee S, Matthies D, Wu X, Milne JL, Subramaniam S. 2.2 a resolution cryo-EM structure of beta-galactosidase in complex with a cell-permeant inhibitor. Science. 2015;348(6239):1147\u201351.","journal-title":"Science"},{"key":"2926_CR6","doi-asserted-by":"crossref","unstructured":"Campbell, M.G., D. Veesler, A. Cheng, C.S. Potter, B. Carragher. 2015. \u201c2.8 a resolution reconstruction of the Thermoplasma acidophilum 20S proteasome using cryo-electron microscopy\u201d, Elife 4.","DOI":"10.7554\/eLife.06380.009"},{"issue":"11","key":"2926_CR7","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1038\/nmeth.4461","volume":"14","author":"Mark A Herzik","year":"2017","unstructured":"Herzik, M.A., Jr., M. Wu, G.C. Lander. 2017. \u201cAchieving better-than-3-a resolution by single-particle cryo-EM at 200 keV.\u201d, Nat Methods 14(11):1075\u20131078.","journal-title":"Nature Methods"},{"issue":"1-2","key":"2926_CR8","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.jsb.2003.09.033","volume":"145","author":"Y Zhu","year":"2004","unstructured":"Zhu Y, Carragher B, Robert M, Glaeser D, Fellmann C, Bajaj M. Automatic particle selection: results of a comparative study. J Struct Biol. 2004:3\u201314.","journal-title":"Journal of Structural Biology"},{"key":"2926_CR9","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1006\/jsbi.2001.4348","volume":"133","author":"RM Glaeser","year":"2001","unstructured":"Glaeser RM, Nicholson WV, Robert M. Review: automatic particle detection in electron. J Struct Biol. 2001;133:90\u2013101.","journal-title":"J Struct Biol"},{"key":"2926_CR10","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.jsb.2003.10.026","volume":"145","author":"PS Umesh Adiga","year":"2004","unstructured":"Umesh Adiga PS, Malladi R, Baxter W, Glaeser RM. A binary segmentation approach for boxing ribosome particles in cryo EM micrographs. Journal of Structural. 2004;145:142\u201351.","journal-title":"Journal of Structural"},{"key":"2926_CR11","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.jsb.2009.01.004","volume":"166","author":"NR Voss","year":"2009","unstructured":"Voss NR, Yoshioka CK, Radermacher M, Potter CS, Carragher B. DoG picker and TiltPicker: software tools to facilitate particle selection in single particle electron microscopy. J Struct Biol. 2009;166:205\u201313.","journal-title":"J Struct Biol"},{"key":"2926_CR12","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.jsb.2012.12.010","volume":"181","author":"J Zhao","year":"2013","unstructured":"Zhao J, Brubaker MA, Rubinstein JL. TMaCS: a hybrid template matching and classification system for partially-automated particle selection. J Struct Biol. 2013;181:234\u201342.","journal-title":"J Struct Biol"},{"key":"2926_CR13","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.str.2015.12.006","volume":"24","author":"Z Liu","year":"2016","unstructured":"Liu Z, Guo F, Wang F, Li T-C, Jiang W. A resolution cryo-em 3d reconstruction of close-packed virus particles. Structure. 2016;24:319\u201328.","journal-title":"Structure"},{"issue":"2","key":"2926_CR14","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.jsb.2013.02.008","volume":"182","author":"Ramin Norousi","year":"2013","unstructured":"Norousi R, Wickles S, Leidig C, Becker T, Schmid VJ, Beckmann R, Tresch A. Automatic post-picking using MAPPOS improves particle image detection from cryo-EM micrographs. J Struct Biol. 2013:59\u201366.","journal-title":"Journal of Structural Biology"},{"key":"2926_CR15","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.jsb.2006.05.004","volume":"157","author":"JZ Grigorieff","year":"2007","unstructured":"Grigorieff JZ, Chen N. SIGNATURE: a single-particle selection system for molecular electron microscopy. J Struct Biol. 2007;157:168\u201373.","journal-title":"J Struct Biol"},{"key":"2926_CR16","unstructured":"Patwardhan, Richard J Hall, Ardan. 2004. \u201cA two step approach for semi-automated particle selection from low contrast cryo-electron micrographs\u201d, J Struct Biol 19\u201328."},{"key":"2926_CR17","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.jsb.2003.11.004","volume":"145","author":"PA Penczek","year":"2004","unstructured":"Penczek PA, Huang Z, Pawel A. Application of template matching technique to particle detection in electron micrographs. J Struct Biol. 2004;145:29\u201340.","journal-title":"J Struct Biol"},{"key":"2926_CR18","doi-asserted-by":"crossref","unstructured":"Langlois R, Pallesen J, Frank J. Reference-free particle selection enhanced hanced with semi-supervised machine learning for cryo-electron microscopy. J Struct Biol. 2011:353\u201361.","DOI":"10.1016\/j.jsb.2011.06.004"},{"issue":"3","key":"2926_CR19","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.jsb.2009.06.011","volume":"167","author":"C.O.S. Sorzano","year":"2009","unstructured":"Sorzano C, Recarte E, Alcorlo M, Bilbao-Castro JR, San-Mart\u0142n C, Marabini R, Carazo JM. Automatic particle selection from electron micrographs using machine learning techniques. J Struct Biol. 2009:252\u201360.","journal-title":"Journal of Structural Biology"},{"key":"2926_CR20","doi-asserted-by":"crossref","unstructured":"Arbelez P, Han B-G, Typke D, Lim J, Glaeser RM, Malik J. Experimental evaluation of support vector machine-based and correlation-based approaches to automatic particle selection. J Struct Biol. 2011:319\u201328.","DOI":"10.1016\/j.jsb.2011.05.017"},{"issue":"3","key":"2926_CR21","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.jsb.2016.07.006","volume":"195","author":"Feng Wang","year":"2016","unstructured":"Wang F, Gong H, Liu G, Li M, Yan C, Xia T, Li X, Zeng J. DeepPicker: a deep learning approach for fully automated particle picking in Cryo-EM. J Struct Biol. 2016:325\u201336.","journal-title":"Journal of Structural Biology"},{"key":"2926_CR22","doi-asserted-by":"crossref","unstructured":"Zhu Y, Ouyang Q, Mao Y. A deep convolutional neural network approach to single-particle recognition in cryo-electron microscopy. BMC Bioinformatics. 2017:2\u201310.","DOI":"10.1186\/s12859-017-1757-y"},{"key":"2926_CR23","unstructured":"MacQueen, J. 1967. \u201cSome methods for classification and analysis of multivariate observations\u201d, in Proc. 5th Berkeley Symp. On math. Stat. And probability. Berkeley, CA. 281\u2013297."},{"issue":"3","key":"2926_CR24","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1080\/01969727308546046","volume":"3","author":"J. C. Dunn","year":"1973","unstructured":"Dunn JC. A fuzzy relative of the ISODATA process and its use in detecting compact well-separated clusters. J Cybern. 1973:32\u201357.","journal-title":"Journal of Cybernetics"},{"key":"2926_CR25","doi-asserted-by":"crossref","unstructured":"G. Tang, L. Peng, P.R. Baldwin, D.S. Mann, W. Jiang, I. Rees & S.J. Ludtke. n.d. \u201cEMAN2: an extensible image processing suite for electron microscopy\u201d, J Struct Biol 157 (PMID: 16859925): 38\u201346.","DOI":"10.1016\/j.jsb.2006.05.009"},{"key":"2926_CR26","first-page":"401","volume-title":"Methods in Molecular Biology","author":"Fei Guo","year":"2013","unstructured":"Guo F., Jiang W. (2014) Single Particle Cryo-electron Microscopy and 3-D Reconstruction of Viruses. In: Kuo J. (eds) Electron Microscopy. Methods in Molecular Biology (Methods and Protocols), vol 1117. Humana Press, Totowa, NJ."},{"key":"2926_CR27","unstructured":"Herv\u2019e, Abdi. 2010. \u201cNormalizing Data\u201d, By Herv\u2019e Abdi. The University of Texas at Dallas: In Neil Salkind (Ed.), Encyclopedia of Research Design."},{"key":"2926_CR28","unstructured":"The MathWorks, Inc. 2018. Image processing toolbox\u2122 User's guide. Natick, MA: The MathWorks, Inc. \n                    https:\/\/www.mathworks.com\/help\/images\/contrast-adjustment.html\n                    \n                  ."},{"key":"2926_CR29","unstructured":"Woods, R. C. Gonzalez, R. E. 2018. \u201cDigital Image Processing\u201d, 4th Edition. University of Tennessee."},{"key":"2926_CR30","unstructured":"Amit Singer,\u201d Mathematics for cryo-electron microscopy\u201d, arXiv:1803.06714v1 [physics.comp-ph] 12 Mar 2018."},{"issue":"1","key":"2926_CR31","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.jsb.2016.04.013","volume":"195","author":"Tejal Bhamre","year":"2016","unstructured":"Bhamre T, Zhang T. Singer A. Denoising and Covariance Estimation of Single Particle Cryo-EM Images. J Struct Bio. 2016. p. 195. \n                    https:\/\/doi.org\/10.1016\/j.jsb.2016.04.013\n                    \n                  .","journal-title":"Journal of Structural Biology"},{"issue":"5","key":"2926_CR32","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1109\/83.841534","volume":"9","author":"J.A. Stark","year":"2000","unstructured":"Stark JA. Adaptive image contrast enhancement using generalizations of histogram equalization. IEEE Trans Image Process. 2000:889\u201369.","journal-title":"IEEE Transactions on Image Processing"},{"key":"2926_CR33","doi-asserted-by":"crossref","unstructured":"He K, Sun J, Tang X. Guided image filtering. IEEE Trans Pattern Anal Mach Intell. 2013.","DOI":"10.1109\/TPAMI.2012.213"},{"key":"2926_CR34","unstructured":"Grant T, Rohou A , Grigorieff N. 2017. EMPIAR-10146. 07 12. Accessed 03 Sept 2018. \n                    https:\/\/www.ebi.ac.uk\/pdbe\/emdb\/empiar\/entry\/10146\/#&gid=1&pid=1\n                    \n                  ."},{"key":"2926_CR35","unstructured":"N.d.,\u201cKLH Dataset\u201d, available Online, \n                    http:\/\/nramm.nysbc.org\/\n                    \n                  ."},{"key":"2926_CR36","unstructured":"Atherton, D. Kerbyson, T. 1995. \u201ccircle detection using Hough transform filters.\u201d proc. 5th Int. Conf. Image process, Appl., U.K. 370\u2013374."},{"key":"2926_CR37","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.jsb.2011.03.009","volume":"175","author":"R Langlois","year":"2011","unstructured":"Langlois R. A clarification of the terms used in comparing semi-automated particle selection algorithms in Cryo-EM. J Struct Biol. 2011;175:348\u201352.","journal-title":"J Struct Biol"},{"issue":"2","key":"2926_CR38","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1109\/TMI.2011.2163944","volume":"31","author":"T. Rohlfing","year":"2012","unstructured":"Rohlfing T. Image similarity and tissue overlaps as surrogates for image registration accuracy: widely used but unreliable. IEEE Trans Med Imaging. 2012:153\u201363.","journal-title":"IEEE Transactions on Medical Imaging"},{"key":"2926_CR39","unstructured":"Steve on Image Processing, \u201c\n                    Feret Properties \u2013 Wrapping Up\n                    \n                  \u201d, concepts, algorithms & MATLAB, \n                    https:\/\/blogs.mathworks.com\/steve\/2018\/04\/17\/feret-properties-wrapping-up\/\n                    \n                  ."}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-019-2926-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12859-019-2926-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-019-2926-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,6,11]],"date-time":"2020-06-11T19:06:11Z","timestamp":1591902371000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-019-2926-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,13]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["2926"],"URL":"https:\/\/doi.org\/10.1186\/s12859-019-2926-y","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/561928","asserted-by":"object"}]},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,13]]},"assertion":[{"value":"19 November 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 May 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 June 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare they have no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"326"}}