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Hi-C based experiments have significantly advanced our understanding chromatin organization. Numerous computational tools have been developed to identify various structural levels of chromatin, ranging from compartments to loops. However, there remains a lack of specialized tools for identifying non-homologous inter-chromatin contacts (NHCCs), which play important roles in chromosome territories. In this study, we present iceDP, a tool that leverages the Density Peaks clustering algorithm to identify local high-density regions within inter-chromatin. These regions undergo two subsequent filtering steps to eliminate obvious false positives. When applied to three Hi-C datasets, iceDP accurately identified known NHCCs, including olfactory receptor genes in mature olfactory sensory neurons and Polycomb repressive complex-regulated developmental genes in mouse embryonic stem cells (mESCs). Notably, iceDP also uncovered previously unreported transcriptionally active NHCCs. Compared to diffHiC and FitHiC, iceDP exhibited superior performance with the highest positive rate. Moreover, iceDP is compatible with a wide range of chromatin conformation capture techniques, including in-situ Hi-C, Micro-C, HiChIP, and BL-HiC, demonstrating its versatility and utility.<\/jats:p>","DOI":"10.1093\/bib\/bbaf704","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T13:02:41Z","timestamp":1766062961000},"source":"Crossref","is-referenced-by-count":0,"title":["iceDP: identifying inter-chromatin engagement via density peaks clustering algorithm"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5907-9954","authenticated-orcid":false,"given":"Ruhai","family":"Chen","sequence":"first","affiliation":[{"name":"Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong Key Laboratory of Non-Human Primate Research, Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Department of Chemistry, Jinan University , No. 601, Huangpu Avenue West, Guangzhou, Guangdong 510632 ,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5168-7074","authenticated-orcid":false,"given":"Jiekai","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Biomedical Digital Science, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences , No. 190 Kaiyuan Avenue, Guangzhou, Guangdong 510530 ,","place":["China"]}]},{"given":"Lingling","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong Key Laboratory of Non-Human Primate Research, Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Department of Chemistry, Jinan University , No. 601, Huangpu Avenue West, Guangzhou, Guangdong 510632 ,","place":["China"]},{"name":"Department of Psychiatry, the First Affiliated Hospital of Jinan University , No. 613, Huangpu Avenue West, Guangzhou, Guangdong 510632 ,","place":["China"]},{"name":"Co-innovation Center of Neuro-regeneration, Nantong University , No. 9, Seyuan Road, Nantong, Jiangsu 226019 ,","place":["China"]}]},{"given":"Jiangping","family":"He","sequence":"additional","affiliation":[{"name":"Faculty of Life and Health Sciences , Shenzhen University of Advanced Technology, No. 1 Gongchang Road, Shenzhen 518107,","place":["China"]},{"name":"Guangzhou National Laboratory , No. 9 Xinghuan Road, 510320\uff0cGuangzhou,","place":["China"]}]}],"member":"286","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"2026010711362020400_ref1","doi-asserted-by":"publisher","first-page":"R185","DOI":"10.1016\/S0960-9822(02)00724-8","article-title":"Order and disorder in the nucleus","volume":"12","author":"Marshall","year":"2002","journal-title":"Curr 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