{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T14:31:30Z","timestamp":1754145090356,"version":"3.41.2"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["1R35GM137974 to Z.W."],"award-info":[{"award-number":["1R35GM137974 to Z.W."]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The 3D organization of chromatin is essential for the functioning of cellular processes, including transcriptional regulation, genome integrity, chromatin accessibility, and higher order nuclear architecture. However, detecting anomalous chromatin interactions in spatiotemporal Hi-C data remains a significant challenge. We present HiC4D-SPOT, an unsupervised deep-learning framework that models chromatin dynamics using a ConvLSTM-based autoencoder to identify structural anomalies. Benchmarking results demonstrate high reconstruction fidelity, with Pearson Correlation Coefficient and Spearman Correlation Coefficient values of 0.9, while accurately detecting deviations linked to temporal inconsistencies, topologically associating domain (TAD) and loop perturbations, and significant chromatin remodeling events. HiC4D-SPOT successfully identifies swapped time points in a time-swap experiment, captures simulated TAD and loop disruptions with high confidence scores and statistical significance of 0.01, and detects HERV-H boundary weakening during cardiomyocyte differentiation, as well as cohesin-mediated loop loss and recovery\u2014aligning with experimentally observed chromatin remodeling events. These findings establish HiC4D-SPOT as an efficient tool for analyzing 3D chromatin dynamics, enabling the detection of biologically significant structural anomalies in spatiotemporal Hi-C data.<\/jats:p>","DOI":"10.1093\/bib\/bbaf341","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T07:53:26Z","timestamp":1750924406000},"source":"Crossref","is-referenced-by-count":0,"title":["HiC4D-SPOT: a spatiotemporal outlier detection tool for Hi-C data"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8330-4348","authenticated-orcid":false,"given":"Bishal","family":"Shrestha","sequence":"first","affiliation":[{"name":"Department of Computer Science, University of Miami, 1365 Memorial Drive , Coral Gables, FL 33146 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3892-6151","authenticated-orcid":false,"given":"Zheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of Miami, 1365 Memorial Drive , Coral Gables, FL 33146 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"2025071610314310800_ref1","first-page":"123","article-title":"The structure of DNA","volume-title":"Cold Spring Harbor Symposia on Quantitative Biology","author":"Watson","year":"1953"},{"key":"2025071610314310800_ref2","first-page":"1304","volume":"291","author":"Craig Venter","year":"2001","journal-title":"The sequence of the human genome. Science"},{"key":"2025071610314310800_ref3","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/j.molcel.2013.02.011","article-title":"The hierarchy of the 3D genome","volume":"49","author":"Gibcus","year":"2013","journal-title":"Mol Cell"},{"key":"2025071610314310800_ref4","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1038\/s41576-018-0060-8","article-title":"Organizational principles of 3D genome architecture","volume":"19","author":"Jordan Rowley","year":"2018","journal-title":"Nat Rev Genet"},{"key":"2025071610314310800_ref5","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/nrg.2016.112","article-title":"Organization and function of the 3D genome","volume":"17","author":"Bonev","year":"2016","journal-title":"Nat Rev Genet"},{"key":"2025071610314310800_ref6","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/s41580-019-0132-4","article-title":"The role of 3D genome organization in development and cell differentiation","volume":"20","author":"Zheng","year":"2019","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2025071610314310800_ref7","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1126\/science.1181369","article-title":"Comprehensive mapping of long-range interactions reveals folding principles of the human genome","volume":"326","author":"Lieberman-Aiden","year":"2009","journal-title":"Science"},{"key":"2025071610314310800_ref8","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.1016\/j.cell.2014.11.021","article-title":"A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping","volume":"159","author":"Rao","year":"2014","journal-title":"Cell"},{"key":"2025071610314310800_ref9","doi-asserted-by":"publisher","first-page":"e198","DOI":"10.1002\/cpz1.198","article-title":"Hi-C 3.0: improved protocol for genome-wide chromosome conformation capture","volume":"1","author":"Lafontaine","year":"2021","journal-title":"Curr Protocols"},{"key":"2025071610314310800_ref10","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/nature11082","article-title":"Topological domains in mammalian genomes identified by analysis of chromatin interactions","volume":"485","author":"Dixon","year":"2012","journal-title":"Nature"},{"key":"2025071610314310800_ref11","doi-asserted-by":"crossref","first-page":"lqaf002","DOI":"10.1093\/nargab\/lqaf002","article-title":"scHiGex: predicting single-cell gene expression based on single-cell Hi-C data","volume":"7","author":"Shrestha","year":"2025","journal-title":"NAR Genomics Bioinf"},{"key":"2025071610314310800_ref12","doi-asserted-by":"publisher","first-page":"2070","DOI":"10.1016\/j.csbj.2021.04.016","article-title":"Application of Hi-C and other omics data analysis in human cancer and cell differentiation research","volume":"19","author":"Gong","year":"2021","journal-title":"Comput Struct Biotechnol J"},{"key":"2025071610314310800_ref13","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1038\/s41580-023-00615-w","article-title":"The technological landscape and applications of single-cell multi-omics","volume":"24","author":"Baysoy","year":"2023","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2025071610314310800_ref14","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/nature23001","article-title":"Cell-cycle dynamics of chromosomal organization at single-cell resolution","volume":"547","author":"Nagano","year":"2017","journal-title":"Nature"},{"key":"2025071610314310800_ref15","doi-asserted-by":"publisher","first-page":"1900986","DOI":"10.1002\/advs.201900986","article-title":"Circular trajectory reconstruction uncovers cell-cycle progression and regulatory dynamics from single-cell hi-c maps","volume":"6","author":"Ye","year":"2019","journal-title":"Adv Sci"},{"key":"2025071610314310800_ref16","doi-asserted-by":"publisher","first-page":"111567","DOI":"10.1016\/j.celrep.2022.111567","article-title":"Temporal analysis suggests a reciprocal relationship between 3D chromatin structure and transcription","volume":"41","author":"Reed","year":"2022","journal-title":"Cell Rep"},{"key":"2025071610314310800_ref17","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1038\/s41577-022-00774-5","article-title":"Three-dimensional genome organization in immune cell fate and function","volume":"23","author":"Cuartero","year":"2023","journal-title":"Nat Rev Immunol"},{"key":"2025071610314310800_ref18","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1038\/nmeth.2148","article-title":"Iterative correction of Hi-C data reveals hallmarks of chromosome organization","volume":"9","author":"Imakaev","year":"2012","journal-title":"Nat Methods"},{"key":"2025071610314310800_ref19","doi-asserted-by":"publisher","first-page":"2902","DOI":"10.1093\/bioinformatics\/btaa048","article-title":"GiniQC: a measure for quantifying noise in single-cell Hi-C data","volume":"36","author":"Horton","year":"2020","journal-title":"Bioinformatics"},{"key":"2025071610314310800_ref20","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s12551-018-0489-1","article-title":"Hi-C analysis: from data generation to integration","volume":"11","author":"Pal","year":"2019","journal-title":"Biophys Rev"},{"key":"2025071610314310800_ref21","doi-asserted-by":"crossref","first-page":"lqz008","DOI":"10.1093\/nargab\/lqz008","article-title":"Analysis of the structural variability of topologically associated domains as revealed by Hi-C","volume":"2","author":"Sauerwald","year":"2020","journal-title":"NAR Genomics Bioinf"},{"key":"2025071610314310800_ref22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13059-019-1658-7","article-title":"Measuring the reproducibility and quality of Hi-C data","volume":"20","author":"Yardimci","year":"2019","journal-title":"Genome Biol"},{"key":"2025071610314310800_ref23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1145\/1541880.1541882","article-title":"Anomaly detection: a survey","volume":"41","author":"Chandola","year":"2009","journal-title":"ACM Comput Surv"},{"key":"2025071610314310800_ref24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1145\/3439950","article-title":"Deep learning for anomaly detection: a review","volume":"54","author":"Pang","year":"2021","journal-title":"ACM Comput Surv"},{"key":"2025071610314310800_ref25","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1016\/j.ajhg.2020.04.016","article-title":"Hi-C identifies complex genomic rearrangements and TAD-shuffling in developmental diseases","volume":"106","author":"Melo","year":"2020","journal-title":"Am J Hum Genet"},{"key":"2025071610314310800_ref26","first-page":", pp. 669","article-title":"A review of anomaly detection techniques using computer vision","volume-title":"Recent Innovations in Computing: Proceedings of ICRIC","author":"Mohindru","year":"2020"},{"key":"2025071610314310800_ref27","article-title":"Adversarial sample generation and training using geometric masks for accurate and resilient license plate character recognition","author":"Shrestha","year":"2023"},{"key":"2025071610314310800_ref28","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.future.2015.01.001","article-title":"A survey of anomaly detection techniques in financial domain","volume":"55","author":"Ahmed","year":"2016","journal-title":"Future Gener Comput Syst"},{"key":"2025071610314310800_ref29","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1109\/ICIRCA51532.2021.9544795","article-title":"Machine learning techniques for anomaly detection in smart healthcare","volume-title":"2021 Third International Conference on Inventive Research in Computing Applications (ICIRCA)","author":"Kavitha","year":"2021"},{"key":"2025071610314310800_ref30","doi-asserted-by":"crossref","first-page":"bbad263","DOI":"10.1093\/bib\/bbad263","article-title":"HiC4D: forecasting spatiotemporal Hi-C data with residual ConvLSTM","volume":"24","author":"Liu","year":"2023","journal-title":"Brief Bioinform"},{"key":"2025071610314310800_ref31","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1038\/s41467-022-29268-7","article-title":"Current progress and open challenges for applying deep learning across the biosciences","volume":"13","author":"Sapoval","year":"2022","journal-title":"Nat Commun"},{"key":"2025071610314310800_ref32","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1146\/annurev-genom-121119-083418","article-title":"Progress, challenges, and surprises in annotating the human genome","volume":"21","author":"Zerbino","year":"2020","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"2025071610314310800_ref33","first-page":"1","article-title":"From data to cure: a comprehensive exploration of multi-omics data analysis for targeted therapies","author":"Mukherjee","year":"2024","journal-title":"Mol Biotechnol"},{"key":"2025071610314310800_ref34","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1109\/CBS.2018.8612259","article-title":"Unsupervised learning based on artificial neural network: a review","volume-title":"2018 IEEE International Conference on Cyborg and Bionic Systems (CBS)","author":"Dike","year":"2018"},{"key":"2025071610314310800_ref35","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1093\/bib\/bbw068","article-title":"Deep learning in bioinformatics","volume":"18","author":"Min","year":"2017","journal-title":"Brief Bioinform"},{"key":"2025071610314310800_ref36","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ymeth.2019.04.008","article-title":"Deep learning in bioinformatics: introduction, application, and perspective in the big data era","volume":"166","author":"Yu","year":"2019","journal-title":"Methods"},{"key":"2025071610314310800_ref37","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/nature23263","article-title":"Allelic reprogramming of 3D chromatin architecture during early mammalian development","volume":"547","author":"Zhenhai","year":"2017","journal-title":"Nature"},{"key":"2025071610314310800_ref38","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1093\/bioinformatics\/btz540","article-title":"Cooler: scalable storage for Hi-C data and other genomically labeled arrays","volume":"36","author":"Abdennur","year":"2020","journal-title":"Bioinformatics"},{"key":"2025071610314310800_ref39","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1038\/s41467-022-29697-4","article-title":"The 4D nucleome data portal as a resource for searching and visualizing curated nucleomics data","volume":"13","author":"Reiff","year":"2022","journal-title":"Nat Commun"},{"key":"2025071610314310800_ref40","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1038\/s41588-019-0479-7","article-title":"Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells","volume":"51","author":"Zhang","year":"2019","journal-title":"Nat Genet"},{"key":"2025071610314310800_ref41","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.cell.2017.09.026","article-title":"Cohesin loss eliminates all loop domains","volume":"171","author":"Rao","year":"2017","journal-title":"Cell"},{"key":"2025071610314310800_ref42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12859-015-0683-0","article-title":"diffHic: a bioconductor package to detect differential genomic interactions in Hi-C data","volume":"16","author":"Lun","year":"2015","journal-title":"BMC Bioinformatics"},{"key":"2025071610314310800_ref43","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/nmeth.4325","article-title":"Comparison of computational methods for Hi-C data analysis","volume":"14","author":"Forcato","year":"2017","journal-title":"Nat Methods"},{"key":"2025071610314310800_ref44","article-title":"PyTorch: an imperative style, high-performance deep learning library","volume-title":"Advances in neural information processing systems","author":"Paszke","year":"2019"},{"key":"2025071610314310800_ref45","doi-asserted-by":"publisher","first-page":"6486","DOI":"10.1109\/TPAMI.2024.3382294","article-title":"Towards understanding convergence and generalization of AdamW","volume":"46","author":"Zhou","year":"2024","journal-title":"IEEE Trans Pattern Anal Mach Intell"},{"key":"2025071610314310800_ref46","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.gde.2016.03.008","article-title":"TAD disruption as oncogenic driver","volume":"36","author":"Valton","year":"2016","journal-title":"Curr Opin Genet Dev"},{"key":"2025071610314310800_ref47","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/s41586-022-05504-4","article-title":"Structural variants drive context-dependent oncogene activation in cancer","volume":"612","author":"Zhichao","year":"2022","journal-title":"Nature"},{"key":"2025071610314310800_ref48","doi-asserted-by":"crossref","first-page":"6130","DOI":"10.1038\/s41467-024-50387-w","article-title":"3D genomic analysis reveals novel enhancer-hijacking caused by complex structural alterations that drive oncogene overexpression","volume":"15","author":"Mortenson","year":"2024","journal-title":"Nat Commun"},{"key":"2025071610314310800_ref49","first-page":"e2402518121","article-title":"Three-dimensional chromatin mapping of sensory neurons reveals that promoter\u2013enhancer looping is required for axonal regeneration","volume-title":"Proceedings of the National Academy of Sciences","author":"Palmisano","year":"2024"},{"key":"2025071610314310800_ref50","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1093\/bfgp\/elz028","article-title":"Order and disorder: abnormal 3D chromatin organization in human disease","volume":"19","author":"Anania","year":"2020","journal-title":"Brief Funct Genomics"},{"key":"2025071610314310800_ref51","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/s41576-020-00325-5","article-title":"Engineering 3D genome organization","volume":"22","author":"Wang","year":"2021","journal-title":"Nat Rev Genet"},{"key":"2025071610314310800_ref52","doi-asserted-by":"publisher","first-page":"W177","DOI":"10.1093\/nar\/gkaa220","article-title":"Galaxy HiCExplorer 3: a web server for reproducible Hi-C, capture Hi-C and single-cell Hi-C data analysis, quality control and visualization","volume":"48","author":"Wolff","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"2025071610314310800_ref53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-019-1893-y","article-title":"OnTAD: hierarchical domain structure reveals the divergence of activity among TADs and boundaries","volume":"20","author":"An","year":"2019","journal-title":"Genome Biol"},{"key":"2025071610314310800_ref54","first-page":"1","article-title":"Mustache: multi-scale detection of chromatin loops from Hi-C and Micro-C maps using scale-space representation","volume":"21","author":"Ardakany","year":"2020","journal-title":"Genome Biol"},{"key":"2025071610314310800_ref55","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1101\/gr.279930.124","article-title":"Examining dynamics of three-dimensional genome organization with multi-task matrix factorization","volume":"35","author":"Lee","year":"2025","journal-title":"Genome Res"},{"key":"2025071610314310800_ref56","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/nature13804","article-title":"Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells","volume":"516","author":"Wang","year":"2014","journal-title":"Nature"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/26\/4\/bbaf341\/63777104\/bbaf341.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/26\/4\/bbaf341\/63777104\/bbaf341.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T14:31:51Z","timestamp":1752676311000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/doi\/10.1093\/bib\/bbaf341\/8203346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":56,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,7,2]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bbaf341","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"value":"1467-5463","type":"print"},{"value":"1477-4054","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,7]]},"published":{"date-parts":[[2025,7]]},"article-number":"bbaf341"}}