{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:13:43Z","timestamp":1789478023588,"version":"build-2803163510"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Progressive optic neuropathies such as glaucoma are major causes of blindness globally. Multiple sources of subjectivity and analytical challenges are often encountered by clinicians in the process of early diagnosis and clinical management of these diseases. In glaucoma, the structural damage is often characterized by neuroretinal rim (NRR) thinning of the optic nerve head, and other clinical parameters. Baseline structural heterogeneity in the eyes can play a key role in the progression of optic neuropathies, and present challenges to clinical decision-making. We generated a dataset of Optical Coherence Tomography (OCT) based high-resolution circular measurements on NRR phenotypes, along with other clinical covariates, of 3973 healthy eyes as part of an established clinical cohort of Asian Indian participants. We introduced CIFU, a new computational pipeline for\n                    <jats:underline>CI<\/jats:underline>\n                    rcular\n                    <jats:underline>FU<\/jats:underline>\n                    nctional data modeling and analysis. We demonstrated CIFU by unsupervised circular functional clustering of the OCT NRR data, followed by meta-clustering to characterize the clusters using clinical covariates, and presented a circular visualization of the results. Upon stratification by age, we identified a healthy NRR phenotype cluster in the age group 40\u201349\u00a0years with predictive potential for glaucoma. Our dataset also addresses the disparity of representation of this particular population in normative OCT databases.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-02025-4","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T06:03:04Z","timestamp":1638424984000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Circular functional analysis of OCT data for precise identification of structural phenotypes in the eye"],"prefix":"10.1038","volume":"11","author":[{"given":"Md. Hasnat","family":"Ali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Wainwright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8184-5739","authenticated-orcid":false,"given":"Alexander","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2076-6957","authenticated-orcid":false,"given":"Ganesh B.","family":"Jonnadula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghana","family":"Desai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5866-9856","authenticated-orcid":false,"given":"Harsha L.","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. B.","family":"Srinivas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Rao","family":"Jammalamadaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirisha","family":"Senthil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saumyadipta","family":"Pyne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"2025_CR1","unstructured":"Global Initiative for the Elimination of Avoidable Blindness: Action Plan 2006\u20132011. (World Health Organization, 2007). https:\/\/apps.who.int\/iris\/handle\/10665\/43754."},{"key":"2025_CR2","doi-asserted-by":"publisher","first-page":"2081","DOI":"10.1016\/j.ophtha.2014.05.013","volume":"121","author":"Y-C Tham","year":"2014","unstructured":"Tham, Y.-C. et al. Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis. Ophthalmology 121, 2081\u20132090 (2014).","journal-title":"Ophthalmology"},{"key":"2025_CR3","first-page":"741","volume":"41","author":"LA Kerrigan-Baumrind","year":"2000","unstructured":"Kerrigan-Baumrind, L. A., Quigley, H. A., Pease, M. E., Kerrigan, D. F. & Mitchell, R. S. Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons. Investig. Ophthalmol. Vis. Sci. 41, 741\u2013748 (2000).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"2025_CR4","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1136\/bjo.81.10.840","volume":"81","author":"D Garway-Heath","year":"1997","unstructured":"Garway-Heath, D., Wollstein, G. & Hitchings, R. Aging changes of the optic nerve head in relation to open angle glaucoma. Br. J. Ophthalmol. 81, 840\u2013845 (1997).","journal-title":"Br. J. Ophthalmol."},{"key":"2025_CR5","first-page":"91","volume":"3","author":"TS Prata","year":"2014","unstructured":"Prata, T. S. et al. Eyes with large disc cupping and normal intraocular pressure: using optical coherence tomography to discriminate those with and without glaucoma. Med. Hypothesis Discov. Innov. Ophthalmol. J. 3, 91\u201398 (2014).","journal-title":"Med. Hypothesis Discov. Innov. Ophthalmol. J."},{"key":"2025_CR6","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1056\/NEJMra0804630","volume":"360","author":"Y Kwon","year":"2009","unstructured":"Kwon, Y., Fingert, J., Kuehm, M. & Alward, W. Primary open-angle glaucoma. N. Engl. J. Med. 360, 1113\u20131124 (2009).","journal-title":"N. Engl. J. Med."},{"key":"2025_CR7","doi-asserted-by":"publisher","first-page":"1684","DOI":"10.1016\/j.ophtha.2010.01.026","volume":"117","author":"CKS Leung","year":"2010","unstructured":"Leung, C. K. S. et al. Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography: Analysis of the retinal nerve fiber layer map for glaucoma detection. Ophthalmology 117, 1684\u20131691 (2010).","journal-title":"Ophthalmology"},{"key":"2025_CR8","doi-asserted-by":"publisher","first-page":"2337","DOI":"10.1016\/j.ophtha.2010.04.002","volume":"117","author":"CKS Leung","year":"2010","unstructured":"Leung, C. K. S. et al. Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography: Pattern of RNFL defects in glaucoma. Ophthalmology 117, 2337\u20132344 (2010).","journal-title":"Ophthalmology"},{"key":"2025_CR9","doi-asserted-by":"publisher","first-page":"5724","DOI":"10.1167\/iovs.10-5222","volume":"51","author":"JC Mwanza","year":"2010","unstructured":"Mwanza, J. C. et al. Reproducibility of peripapillary retinal nerve fiber layer thickness and optic nerve head parameters measured with cirrus HD-OCT in glaucomatous eyes. Investig. Ophthalmol. Vis. Sci. 51, 5724\u20135730 (2010).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"2025_CR10","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.ophtha.2010.06.036","volume":"118","author":"JC Mwanza","year":"2011","unstructured":"Mwanza, J. C., Oakley, J. D., Budenz, D. L. & Anderson, D. R. Ability of cirrus HD-OCT optic nerve head parameters to discriminate normal from glaucomatous eyes. Ophthalmology 118, 241-248.e1 (2011).","journal-title":"Ophthalmology"},{"key":"2025_CR11","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1097\/IJG.0b013e318220dbb7","volume":"21","author":"KR Sung","year":"2012","unstructured":"Sung, K. R., Na, J. H. & Lee, Y. Glaucoma diagnostic capabilities of optic nerve head parameters as determined by cirrus HD optical coherence tomography. J. Glaucoma 21, 498\u2013504 (2012).","journal-title":"J. Glaucoma"},{"key":"2025_CR12","doi-asserted-by":"publisher","DOI":"10.1142\/4031","volume-title":"Topics in Circular Statistics","author":"SR Jammalamadaka","year":"2001","unstructured":"Jammalamadaka, S. R. & SenGupta, A. Topics in Circular Statistics (World Scientific, 2001)."},{"key":"2025_CR13","first-page":"401","volume":"62","author":"F Ieva","year":"2012","unstructured":"Ieva, F., Paganoni, A. M., Davide, P. & Valeria, V. Multivariate functional clustering for the morphological analysis of electrocardiograph curves. Appl. Stat. 62, 401\u2013418 (2012).","journal-title":"Appl. Stat."},{"key":"2025_CR14","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.neucom.2012.11.042","volume":"112","author":"J Jacques","year":"2013","unstructured":"Jacques, J. & Preda, C. Funclust: A curves clustering method using functional random variables density approximation. Neurocomputing 112, 164\u2013171 (2013).","journal-title":"Neurocomputing"},{"key":"2025_CR15","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1146\/annurev-statistics-041715-033624","volume":"3","author":"J-L Wang","year":"2016","unstructured":"Wang, J.-L., Chiou, J.-M. & M\u00fcller, H.-G. Functional data analysis. Annu. Rev. Stat. Appl. 3, 257\u2013295 (2016).","journal-title":"Annu. Rev. Stat. Appl."},{"key":"2025_CR16","first-page":"109","volume-title":"Statistical Sciences and Data Analysis","author":"SR Jammalamadaka","year":"1993","unstructured":"Jammalamadaka, S. R. & Sarma, Y. Circular regression. In Statistical Sciences and Data Analysis (eds Matusita, K. et al.) 109\u2013128 (VSP Intl Science, 1993)."},{"key":"2025_CR17","volume-title":"Cirrus HD-OCT User Manual","author":"Carl Zeiss Meditec Inc","year":"2015","unstructured":"Carl Zeiss Meditec Inc. Cirrus HD-OCT User Manual (Carl Zeiss Meditec Inc, 2015)."},{"key":"2025_CR18","first-page":"323","volume":"72","author":"B Thylefors","year":"1994","unstructured":"Thylefors, B. & N\u00e9grel, A. The global impact of glaucoma. Bull. World Health Organ 72, 323\u2013326 (1994).","journal-title":"Bull. World Health Organ"},{"key":"2025_CR19","doi-asserted-by":"publisher","first-page":"188","DOI":"10.3109\/09286586.2013.792938","volume":"20","author":"UK Addepalli","year":"2013","unstructured":"Addepalli, U. K. et al. LV Prasad Eye Institute Glaucoma Epidemiology and Molecular Genetic Study (LVPEI-GLEAMS). Report 1: study design and research methodology. Ophthalmic Epidemiol. 20, 188\u2013195 (2013).","journal-title":"Ophthalmic Epidemiol."},{"key":"2025_CR20","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1016\/j.ajo.2013.12.012","volume":"157","author":"H Rao","year":"2014","unstructured":"Rao, H. et al. Effect of scan quality on diagnostic accuracy of spectral-domain optical coherence tomography in glaucoma. Am. J. Ophthalmol. 157, 719\u2013727 (2014).","journal-title":"Am. J. Ophthalmol."},{"key":"2025_CR21","doi-asserted-by":"publisher","first-page":"4471","DOI":"10.1167\/iovs.09-3892","volume":"51","author":"C Samarawickrama","year":"2010","unstructured":"Samarawickrama, C. et al. Influence of OCT signal strength on macular, optic nerve head, and retinal nerve fiber layer parameters. Invest. Ophthalmol. Vis. Sci. 51, 4471\u20134475 (2010).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2025_CR22","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1097\/IJG.0b013e31817eee20","volume":"18","author":"Z Wu","year":"2009","unstructured":"Wu, Z., Huang, J., Dustin, L. & Sadda, S. Signal strength is an important determinant of accuracy of nerve fiber layer thickness measurement by optical coherence tomography. J. Glaucoma 18, 213\u2013216 (2009).","journal-title":"J. Glaucoma"},{"key":"2025_CR23","first-page":"1726","volume":"4","author":"C Bouveyron","year":"2015","unstructured":"Bouveyron, C., C\u00f4me, E. & Jacques, J. The discriminative functional mixture model for a comparative analysis of bike sharing systems. Ann. Appl. Stat. 4, 1726\u20131760 (2015).","journal-title":"Ann. Appl. Stat."},{"key":"2025_CR24","unstructured":"CRAN\u2014Package funFEM. https:\/\/cran.r-project.org\/web\/packages\/funFEM\/index.html."},{"key":"2025_CR25","volume-title":"The EM Algorithm and Extensions. Wiley Series in Probability and Statistics","author":"GJ McLachlan","year":"2008","unstructured":"McLachlan, G. J. & Krishnan, T. The EM Algorithm and Extensions. Wiley Series in Probability and Statistics (Wiley, 2008)."},{"key":"2025_CR26","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/s003579900058","volume":"16","author":"C Fraley","year":"1999","unstructured":"Fraley, C. & Raftery, A. E. MCLUST: Software for model-based cluster analysis. J. Classif. 16, 297\u2013306 (1999).","journal-title":"J. Classif."},{"key":"2025_CR27","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1109\/TAC.1974.1100705","volume":"19","author":"H Akaike","year":"1974","unstructured":"Akaike, H. A new look at the statistical model identification. IEEE Trans. Autom. Control 19, 716\u2013723 (1974).","journal-title":"IEEE Trans. Autom. Control"},{"key":"2025_CR28","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1109\/34.865189","volume":"22","author":"C Biernacki","year":"2000","unstructured":"Biernacki, C., Celeux, G. & Govaert, G. Assessing a mixture model for clustering with the integrated completed likelihood. IEEE Trans. Pattern Anal. Mach. Intell. 22, 719\u2013725 (2000).","journal-title":"IEEE Trans. Pattern Anal. Mach. Intell."},{"key":"2025_CR29","doi-asserted-by":"publisher","first-page":"455","DOI":"10.2307\/3315327","volume":"24","author":"L Manchester","year":"1996","unstructured":"Manchester, L. & Blanchard, W. When is a curve an outlier? An account of a tricky problem. Can. J. Stat. 24, 455\u2013466 (1996).","journal-title":"Can. J. Stat."},{"key":"2025_CR30","volume-title":"Finding Groups in Data: An Introduction to Cluster Analysis","author":"L Kaufman","year":"2005","unstructured":"Kaufman, L. & Rousseeuw, P. J. Finding Groups in Data: An Introduction to Cluster Analysis (Wiley, 2005)."},{"key":"2025_CR31","doi-asserted-by":"publisher","first-page":"101","DOI":"10.6026\/97320630013101","volume":"13","author":"M Sekula","year":"2017","unstructured":"Sekula, M., Datta, S. & Datta, S. optCluster: An R package for determining the optimal clustering algorithm. Bioinformation 13, 101 (2017).","journal-title":"Bioinformation"},{"key":"2025_CR32","unstructured":"CRAN\u2014Package factoextra. https:\/\/cran.r-project.org\/web\/packages\/factoextra\/index.html."},{"key":"2025_CR33","unstructured":"CRAN\u2014Package sparcl. https:\/\/cran.r-project.org\/web\/packages\/sparcl\/index.html."},{"key":"2025_CR34","first-page":"1151","volume":"29","author":"JB Jonas","year":"1988","unstructured":"Jonas, J. B., Gusek, G. C. & Naumann, G. O. Optic disc, cup and neuroretinal rim size, configuration and correlations in normal eyes. Invest. Ophthalmol. Vis. Sci. 29, 1151\u20131158 (1988).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2025_CR35","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1136\/bjophthalmol-2019-314894","volume":"104","author":"Y Tao","year":"2020","unstructured":"Tao, Y. et al. Profile of retinal nerve fibre layer symmetry in a multiethnic Asian population: The Singapore Epidemiology of Eye Diseases study. Br. J. Ophthalmol. 104, 836\u2013841 (2020).","journal-title":"Br. J. Ophthalmol."},{"key":"2025_CR36","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.ajo.2018.08.050","volume":"196","author":"C Bowd","year":"2018","unstructured":"Bowd, C. et al. Racial differences in rate of change of spectral domain OCT-measured minimum rim width and retinal nerve fiber layer thickness. Am. J. Ophthalmol. 196, 154\u2013164 (2018).","journal-title":"Am. J. Ophthalmol."},{"key":"2025_CR37","doi-asserted-by":"publisher","first-page":"1786","DOI":"10.1016\/j.ophtha.2015.06.001","volume":"122","author":"BC Chauhan","year":"2015","unstructured":"Chauhan, B. C. et al. Bruch\u2019s membrane opening-minimum rim width and retinal nerve fibre layer thickness in a normal white population. A Multi-centre study. Ophthalmology 122, 1786\u20131794 (2015).","journal-title":"Ophthalmology"},{"key":"2025_CR38","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1001\/archopthalmol.2011.1576","volume":"130","author":"OJ Knight","year":"2012","unstructured":"Knight, O. J., Girkin, C. A., Budenz, D. L., Durbin, M. K. & Feuer, W. J. Effect of race, age, and axial length on optic nerve head parameters and retinal nerve fiber layer thickness measured by cirrus HD-OCT. Arch. Ophthalmol. 130, 312\u2013318 (2012).","journal-title":"Arch. Ophthalmol."},{"key":"2025_CR39","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1136\/bjo.2005.081224","volume":"90","author":"H Quigley","year":"2006","unstructured":"Quigley, H. & Broman, A. T. The number of people with glaucoma worldwide in 2010 and 2020. Br. J. Ophthalmol. 90, 262\u2013267 (2006).","journal-title":"Br. J. Ophthalmol."},{"key":"2025_CR40","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.ophtha.2009.06.062","volume":"117","author":"HL Rao","year":"2010","unstructured":"Rao, H. L., Babu, G. J. & Sekhar, G. C. Comparison of the diagnostic capability of the Heidelberg retina tomographs 2 and 3 for glaucoma in the Indian population. Ophthalmology 117, 275\u2013281 (2010).","journal-title":"Ophthalmology"},{"key":"2025_CR41","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1016\/j.ophtha.2015.11.018","volume":"123","author":"N Hammel","year":"2016","unstructured":"Hammel, N. et al. Rate and pattern of rim area loss in healthy and progressing glaucoma eyes. Ophthalmology 123, 760\u2013770 (2016).","journal-title":"Ophthalmology"},{"key":"2025_CR42","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1136\/bjo.82.10.1118","volume":"82","author":"DF Garway-Heath","year":"1998","unstructured":"Garway-Heath, D. F., Ruben, S. T., Viswanathan, A. & Hitchings, R. A. Vertical cup\/disc ratio in relation to optic disc size: Its value in the assessment of the glaucoma suspect. Br. J. Ophthalmol. 82, 1118\u20131124 (1998).","journal-title":"Br. J. Ophthalmol."},{"key":"2025_CR43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0236819","volume":"15","author":"B Siesky","year":"2020","unstructured":"Siesky, B. et al. Baseline structural characteristics of the optic nerve head and retinal nerve fiber layer are associated with progressive visual field loss in patients with open-angle glaucoma. PLoS ONE 15, 1\u201311 (2020).","journal-title":"PLoS ONE"},{"key":"2025_CR44","doi-asserted-by":"publisher","first-page":"1852","DOI":"10.1167\/iovs.11-9309","volume":"53","author":"ASC Reis","year":"2012","unstructured":"Reis, A. S. C. et al. Influence of clinically invisible, but optical coherence tomography detected, optic disc margin anatomy on neuroretinal rim evaluation. Invest. Ophthalmol. Vis. Sci. 53, 1852\u20131860 (2012).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2025_CR45","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1136\/bjo.82.4.352","volume":"82","author":"DF Garway-Heath","year":"1998","unstructured":"Garway-Heath, D. F. & Hitchings, R. A. Quantitative evaluation of the optic nerve head in early glaucoma. Br. J. Ophthalmol. 82, 352\u2013361 (1998).","journal-title":"Br. J. Ophthalmol."},{"key":"2025_CR46","volume-title":"Statistical Shape Analysis: With Applications in R. Wiley Series in Probability and Statistics","author":"IL Dryden","year":"2016","unstructured":"Dryden, I. L. & Mardia, K. V. Statistical Shape Analysis: With Applications in R. Wiley Series in Probability and Statistics 2nd edn. (Wiley, 2016).","edition":"2"},{"key":"2025_CR47","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1002\/sim.5589","volume":"32","author":"C Abraham","year":"2013","unstructured":"Abraham, C., Molinari, N. & Servien, R. Unsupervised clustering of multivariate circular data. Stat. Med. 32, 1376\u20131382 (2013).","journal-title":"Stat. Med."},{"key":"2025_CR48","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez, C. E., N\u00fa\u00f1ez-Antonio, G. & Escarela, G. A Bayesian mixture model for clustering circular data. Comput. Stat. Data Anal. 143, 106842 (2020).","DOI":"10.1016\/j.csda.2019.106842"},{"key":"2025_CR49","unstructured":"Gaffney, S. & Smyth, P. Joint probabilistic curve clustering and alignment. In Proceedings of the 17th International Conference on Neural Information Processing Systems 473\u2013480 (2004)."},{"key":"2025_CR50","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1198\/016214505000000187","volume":"101","author":"NA Heard","year":"2006","unstructured":"Heard, N. A., Holmes, C. C. & Stephens, D. A. A quantitative study of gene regulation involved in the immune response of Anopheline mosquitoes: An application of Bayesian hierarchical clustering of curves. J. Am. Stat. Assoc. 101, 18\u201329 (2006).","journal-title":"J. Am. Stat. Assoc."},{"key":"2025_CR51","doi-asserted-by":"publisher","first-page":"e35693","DOI":"10.1371\/journal.pone.0035693","volume":"7","author":"S Ray","year":"2012","unstructured":"Ray, S. & Pyne, S. A computational framework to emulate the human perspective in flow cytometric data analysis. PLoS ONE 7, e35693 (2012).","journal-title":"PLoS ONE"},{"key":"2025_CR52","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1198\/016214503000189","volume":"98","author":"GM James","year":"2003","unstructured":"James, G. M. & Sugar, C. A. Clustering for sparsely sampled functional data. J. Am. Stat. Assoc. 98, 397\u2013408 (2003).","journal-title":"J. Am. Stat. Assoc."},{"key":"2025_CR53","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1111\/j.1467-842X.1992.tb01356.x","volume":"34","author":"PN Jones","year":"1992","unstructured":"Jones, P. N. & McLachlan, G. J. Fitting finite mixture models in a regression context. Aust. J. Stat. 34, 233\u2013240 (1992).","journal-title":"Aust. J. Stat."},{"key":"2025_CR54","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1111\/j.1467-9868.2006.00545.x","volume":"68","author":"S Ray","year":"2006","unstructured":"Ray, S. & Mallick, B. Functional clustering by Bayesian wavelet methods. J. R. Stat. Soc. Ser. B 68, 305\u2013332 (2006).","journal-title":"J. R. Stat. Soc. Ser. B"},{"key":"2025_CR55","doi-asserted-by":"publisher","first-page":"2226","DOI":"10.1167\/iovs.11-8689","volume":"53","author":"YH Hwang","year":"2012","unstructured":"Hwang, Y. H. & Kim, Y. Y. Glaucoma diagnostic ability of quadrant and clock-hour neuroretinal rim assessment using cirrus HD optical coherence tomography. Invest. Ophthalmol. Vis. Sci. 53, 2226\u20132234 (2012).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2025_CR56","doi-asserted-by":"publisher","first-page":"8519","DOI":"10.1073\/pnas.0903028106","volume":"106","author":"S Pyne","year":"2009","unstructured":"Pyne, S. et al. Automated high-dimensional flow cytometric data analysis. PNAS 106, 8519\u20138524 (2009).","journal-title":"PNAS"},{"key":"2025_CR57","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1007\/s11222-010-9225-9","volume":"22","author":"H Ho","year":"2012","unstructured":"Ho, H., Pyne, S. & Lin, T. Maximum likelihood inference for mixtures of skew Student-t-normal distributions through practical EM-type algorithms. Stat. Comput. 22, 287\u2013299 (2012).","journal-title":"Stat. Comput."},{"key":"2025_CR58","doi-asserted-by":"publisher","first-page":"e100334","DOI":"10.1371\/journal.pone.0100334","volume":"9","author":"S Pyne","year":"2014","unstructured":"Pyne, S. et al. Joint modeling and registration of cell populations in cohorts of high-dimensional flowcytometric data. PLoS ONE 9, e100334 (2014).","journal-title":"PLoS ONE"},{"key":"2025_CR59","doi-asserted-by":"publisher","first-page":"e0228651","DOI":"10.1371\/journal.pone.0228651","volume":"15","author":"Y Qi","year":"2020","unstructured":"Qi, Y. et al. High-speed automaticcharacterization of rare events in flow cytometric data. PLoS ONE 15, e0228651 (2020).","journal-title":"PLoS ONE"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-02025-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-02025-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-02025-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T13:06:45Z","timestamp":1675948005000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-02025-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,2]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["2025"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-02025-4","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.02.07.21251275","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,2]]},"assertion":[{"value":"31 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"23336"}}