{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:36:28Z","timestamp":1792794988941,"version":"4.5.0"},"posted":{"date-parts":[[2025,10,24]]},"group-title":"Bioinformatics","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Canadian Institutes of Health Research","award":["CIHR: PJT-175112"],"award-info":[{"award-number":["CIHR: PJT-175112"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Natural Sciences and Engineering Research Council of Canada","award":["NSERC: RGPIN-2019-05179"],"award-info":[{"award-number":["NSERC: RGPIN-2019-05179"]}],"id":[{"id":"https:\/\/ror.org\/01h531d29","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Natural Sciences and Engineering Research Council of Canada","award":["NSERC: RGPIN-2020-06752"],"award-info":[{"award-number":["NSERC: RGPIN-2020-06752"]}],"id":[{"id":"https:\/\/ror.org\/01h531d29","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institutes of Health","award":["NHGRI: RM1HG011016"],"award-info":[{"award-number":["NHGRI: RM1HG011016"]}]},{"name":"National Institutes of Health","award":["NHGRI: UM1HG011593"],"award-info":[{"award-number":["NHGRI: UM1HG011593"]}]},{"name":"Genome Imaging Fund of Harvard Medical School"},{"name":"Birzeit University","id":[{"id":"https:\/\/ror.org\/0256kw398","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/014geb094","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Clustering is a fundamental task in data analysis: grouping similar objects together into distinguishable subsets. Here, we introduce HDCluster, a novel high-degree graph-based clustering algorithm designed to effectively and rapidly handle various real-world clustering applications, particularly in the context of super-resolution single molecule localization microscopy (SMLM). HDCluster efficiently handles datasets with large and variable numbers of clusters, without requiring prior knowledge of the cluster count, relying on only one parameter. The high speed and efficiency of HDCluster allow it to handle large SMLM datasets with millions of localizations. A comprehensive quantitative comparison shows that HDCluster is equivalent to state-of-the-art clustering methods based on clustering performance measures, such as ARI and AMI, on simulated datasets. In terms of time efficiency, HDCluster significantly outperforms other clustering algorithms on large DNA-PAINT datasets. Application of HDCluster to a neuronal DNA-PAINT dataset on synapse biology identified and removed multiple blinking artifacts and effectively identified excitatory and inhibitory synapses, highlighting its utility for real experimental DNA-PAINT data. HDCluster is particularly robust to noise, making it a promising and effective tool for various clustering tasks in big-data settings, such as SMLM DNA-PAINT datasets.<\/jats:p>","DOI":"10.1101\/2025.10.23.684134","type":"posted-content","created":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T02:45:11Z","timestamp":1761360311000},"source":"Crossref","is-referenced-by-count":1,"title":["HDCluster: High-Degree Graph Clustering for Robust Analysis of Single Molecule Localization Microscopy"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7827-7745","authenticated-orcid":false,"given":"Ismail M.","family":"Khater","sequence":"first","affiliation":[{"name":"Department of Electrical and Computer Engineering, Faculty of Engineering and Technology, Birzeit University, Birzeit P627, Palestine"},{"name":"Medical Image Analysis Lab, School of Computing Science, Simon Fraser University, Burnaby, BC V5A 1S6, Canada"},{"name":"Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Benyamin","family":"Bagheri","sequence":"additional","affiliation":[{"name":"Life Sciences Institute, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5344-0053","authenticated-orcid":false,"given":"Shane J.","family":"Eastwood","sequence":"additional","affiliation":[{"name":"Medical Image Analysis Lab, School of Computing Science, Simon Fraser University, Burnaby, BC V5A 1S6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0670-0513","authenticated-orcid":false,"given":"Ivan Robert","family":"Nabi","sequence":"additional","affiliation":[{"name":"Life Sciences Institute, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"},{"name":"School of Biomedical Engineering, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5040-7448","authenticated-orcid":false,"given":"Ghassan","family":"Hamarneh","sequence":"additional","affiliation":[{"name":"Medical Image Analysis Lab, School of Computing Science, Simon Fraser University, Burnaby, BC V5A 1S6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026102113552527000_2025.10.23.684134v2.1","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1145\/331499.331504","article-title":"Data clustering: a review","volume":"31","year":"1999","journal-title":"ACM Comput. Surv"},{"key":"2026102113552527000_2025.10.23.684134v2.2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1127344"},{"key":"2026102113552527000_2025.10.23.684134v2.3","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth929"},{"key":"2026102113552527000_2025.10.23.684134v2.4","doi-asserted-by":"crossref","unstructured":"Shashkova, S. & Leake, M. C . Single-molecule fluorescence microscopy review: shedding new light on old problems. Biosci. Rep. 37, (2017).","DOI":"10.1042\/BSR20170031"},{"key":"2026102113552527000_2025.10.23.684134v2.5","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2835"},{"key":"2026102113552527000_2025.10.23.684134v2.6","doi-asserted-by":"publisher","DOI":"10.1126\/science.aak9913"},{"key":"2026102113552527000_2025.10.23.684134v2.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05925-9"},{"key":"2026102113552527000_2025.10.23.684134v2.8","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.6b00667"},{"key":"2026102113552527000_2025.10.23.684134v2.9","doi-asserted-by":"publisher","DOI":"10.1002\/jbio.200900089"},{"key":"2026102113552527000_2025.10.23.684134v2.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.01.054"},{"key":"2026102113552527000_2025.10.23.684134v2.11","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4642"},{"key":"2026102113552527000_2025.10.23.684134v2.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.patter.2020.100038"},{"key":"2026102113552527000_2025.10.23.684134v2.13","doi-asserted-by":"publisher","DOI":"10.1109\/TNN.2005.845141"},{"key":"2026102113552527000_2025.10.23.684134v2.14","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3804"},{"key":"2026102113552527000_2025.10.23.684134v2.15","doi-asserted-by":"publisher","DOI":"10.1007\/BF01908075"},{"key":"2026102113552527000_2025.10.23.684134v2.16","doi-asserted-by":"publisher","DOI":"10.5555\/1756006.1953024"},{"key":"2026102113552527000_2025.10.23.684134v2.17","doi-asserted-by":"publisher","DOI":"10.1007\/s40745-015-0040-1"},{"key":"2026102113552527000_2025.10.23.684134v2.18","doi-asserted-by":"crossref","first-page":"9693","DOI":"10.1038\/s41467-025-65557-7","article-title":"Enhanced spatial clustering of single-molecule localizations with graph neural networks","volume":"16","year":"2025","journal-title":"Nat. Commun"},{"key":"2026102113552527000_2025.10.23.684134v2.19","doi-asserted-by":"crossref","first-page":"4743","DOI":"10.1007\/s10489-018-1238-7","article-title":"K-means properties on six clustering benchmark datasets","volume":"48","year":"2018","journal-title":"Appl. Intell"},{"key":"2026102113552527000_2025.10.23.684134v2.20","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1109\/TPAMI.2019.2924953","article-title":"Border-peeling clustering","volume":"42","year":"2020","journal-title":"IEEE Trans. Pattern Anal. Mach. Intell"},{"key":"2026102113552527000_2025.10.23.684134v2.21","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s10994-016-5608-2","article-title":"QCC: a novel clustering algorithm based on Quasi-Cluster Centers","volume":"106","year":"2017","journal-title":"Mach. Learn"},{"key":"2026102113552527000_2025.10.23.684134v2.22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1700770114"},{"key":"2026102113552527000_2025.10.23.684134v2.23","doi-asserted-by":"publisher","DOI":"10.1126\/science.1242072"},{"key":"2026102113552527000_2025.10.23.684134v2.24","doi-asserted-by":"publisher","DOI":"10.1109\/34.1000236"},{"key":"2026102113552527000_2025.10.23.684134v2.25","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4314"},{"key":"2026102113552527000_2025.10.23.684134v2.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01750-6"},{"key":"2026102113552527000_2025.10.23.684134v2.27","doi-asserted-by":"publisher","DOI":"10.1093\/BIOINFORMATICS\/BTZ788"},{"key":"2026102113552527000_2025.10.23.684134v2.28","doi-asserted-by":"crossref","unstructured":"Silverman, B. W . Density Estimation for Statistics and Data Analysis. (Routledge, 2018).","DOI":"10.1201\/9781315140919"},{"key":"2026102113552527000_2025.10.23.684134v2.29","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv630"},{"key":"2026102113552527000_2025.10.23.684134v2.30","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1038\/s41467-020-15293-x","article-title":"Machine learning for cluster analysis of localization microscopy data","volume":"11","year":"2020","journal-title":"Nat. Commun"},{"key":"2026102113552527000_2025.10.23.684134v2.31","doi-asserted-by":"publisher","DOI":"10.1038\/srep24084"},{"key":"2026102113552527000_2025.10.23.684134v2.32","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3579"},{"key":"2026102113552527000_2025.10.23.684134v2.33","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.2512.19772"},{"key":"2026102113552527000_2025.10.23.684134v2.34","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-46174-z"},{"key":"2026102113552527000_2025.10.23.684134v2.35","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-64228-x"},{"key":"2026102113552527000_2025.10.23.684134v2.36","doi-asserted-by":"crossref","unstructured":"Wang, Y. , Gu, Y. & Shun, J. Theoretically-efficient and practical parallel DBSCAN. in Proceedings of the 2020 ACM SIGMOD International Conference on Management of Data 2555\u20132571 (ACM, New York, NY, USA, 2020).","DOI":"10.1145\/3318464.3380582"},{"key":"2026102113552527000_2025.10.23.684134v2.37","unstructured":"The MathWorks, Inc. DBSCAN: Density-based clustering. MATLAB Documentation. https:\/\/www.mathworks.com\/help\/stats\/dbscan.html."},{"key":"2026102113552527000_2025.10.23.684134v2.38","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-59500-z"},{"key":"2026102113552527000_2025.10.23.684134v2.39","doi-asserted-by":"publisher","DOI":"10.1021\/acssensors.5c00616"},{"key":"2026102113552527000_2025.10.23.684134v2.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.02.045"},{"key":"2026102113552527000_2025.10.23.684134v2.41","doi-asserted-by":"crossref","first-page":"103637","DOI":"10.1016\/j.xpro.2025.103637","article-title":"Protocol for SUM-PAINT spatial proteomic imaging generating neuronal architecture maps in rat hippocampal neurons","volume":"6","year":"2025","journal-title":"STAR Protoc"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.10.23.684134","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:55:35Z","timestamp":1792616135000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.10.23.684134"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,24]]},"references-count":41,"URL":"https:\/\/doi.org\/10.1101\/2025.10.23.684134","relation":{},"subject":[],"published":{"date-parts":[[2025,10,24]]},"subtype":"preprint"}}