Integration of chromosome conformation and gene expression networks reveals regulatory mechanisms in triple negative breast cancer
IntroductionTriple-negative breast cancer (TNBC) accounts for twelve percent of all breast cancer cases, with a survival rate around ten percent lower than ER+/PR+ positive breast cancers. There are limited therapeutic options as these tumors do not respond to hormonal therapy or HER2-targeted treat...
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Frontiers Media S.A.
2025-07-01
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| author | Helena Reyes-Gopar Helena Reyes-Gopar Helena Reyes-Gopar Keila Adonai Pérez-Fuentes Matthew L. Bendall Enrique Hernández-Lemus Enrique Hernández-Lemus |
| author_facet | Helena Reyes-Gopar Helena Reyes-Gopar Helena Reyes-Gopar Keila Adonai Pérez-Fuentes Matthew L. Bendall Enrique Hernández-Lemus Enrique Hernández-Lemus |
| author_sort | Helena Reyes-Gopar |
| collection | DOAJ |
| description | IntroductionTriple-negative breast cancer (TNBC) accounts for twelve percent of all breast cancer cases, with a survival rate around ten percent lower than ER+/PR+ positive breast cancers. There are limited therapeutic options as these tumors do not respond to hormonal therapy or HER2-targeted treatments. We hypothesized that new insights into pathogenic mechanisms in TNBC can be obtained from studying epigenetic alterations through Hi-C (genome-wide chromosome conformation capture) data analysis.MethodsWe developed a computational strategy that captured key properties of chromatin conformation while incorporating statistical measures of interaction significance. This model addresses limitations in Hi-C data analysis without relying on predefined features like TADs and compartments. We applied this model to Hi-C and RNA-seq data from TNBC patients, representing the data as multilayer networks to identify genome-wide properties of the TNBC 3D genome.ResultsOur network-based analysis revealed distinct chromatin interaction patterns in TNBC compared to healthy contralateral controls. Hi-C data can distinguish interaction patterns related to diseased phenotypes or interaction patterns with potential to exert regulatory effects instead of incidental contacts, but some apparently random interactions may also support important genome regulatory activities.DiscussionOur findings demonstrate that network-based Hi-C analysis can capture the genome-wide complexity of chromatin interactions in TNBC. This integrative approach provides new insights into the epigenetic mechanisms underlying TNBC pathogenesis and contributes to the advancement of analysis methods for future investigations into novel therapeutic targets. |
| format | Article |
| id | doaj-art-4399c3241fba4cd5a858cc0eba291cdd |
| institution | Kabale University |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-4399c3241fba4cd5a858cc0eba291cdd2025-08-20T03:29:45ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-07-011310.3389/fcell.2025.15972451597245Integration of chromosome conformation and gene expression networks reveals regulatory mechanisms in triple negative breast cancerHelena Reyes-Gopar0Helena Reyes-Gopar1Helena Reyes-Gopar2Keila Adonai Pérez-Fuentes3Matthew L. Bendall4Enrique Hernández-Lemus5Enrique Hernández-Lemus6Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México, Mexico City, MexicoFeinstein Institutes for Medical Research, Northwell Health, Institute of Translational Research, Manhasset, NY, United StatesComputational Genomics Division, National Institute of Genomic Medicine, Mexico City, MexicoComputational Genomics Division, National Institute of Genomic Medicine, Mexico City, MexicoWeill Cornell Medicine, Division of Infectious Diseases, New York, NY, United StatesComputational Genomics Division, National Institute of Genomic Medicine, Mexico City, MexicoCentro de Ciencias de la Complejidad, Universidad Nacional Autónoma de México, Mexico City, MexicoIntroductionTriple-negative breast cancer (TNBC) accounts for twelve percent of all breast cancer cases, with a survival rate around ten percent lower than ER+/PR+ positive breast cancers. There are limited therapeutic options as these tumors do not respond to hormonal therapy or HER2-targeted treatments. We hypothesized that new insights into pathogenic mechanisms in TNBC can be obtained from studying epigenetic alterations through Hi-C (genome-wide chromosome conformation capture) data analysis.MethodsWe developed a computational strategy that captured key properties of chromatin conformation while incorporating statistical measures of interaction significance. This model addresses limitations in Hi-C data analysis without relying on predefined features like TADs and compartments. We applied this model to Hi-C and RNA-seq data from TNBC patients, representing the data as multilayer networks to identify genome-wide properties of the TNBC 3D genome.ResultsOur network-based analysis revealed distinct chromatin interaction patterns in TNBC compared to healthy contralateral controls. Hi-C data can distinguish interaction patterns related to diseased phenotypes or interaction patterns with potential to exert regulatory effects instead of incidental contacts, but some apparently random interactions may also support important genome regulatory activities.DiscussionOur findings demonstrate that network-based Hi-C analysis can capture the genome-wide complexity of chromatin interactions in TNBC. This integrative approach provides new insights into the epigenetic mechanisms underlying TNBC pathogenesis and contributes to the advancement of analysis methods for future investigations into novel therapeutic targets.https://www.frontiersin.org/articles/10.3389/fcell.2025.1597245/fulltriple negative breast cancerchromosome conformation capturehi-ccomplex networksregulatory genomics |
| spellingShingle | Helena Reyes-Gopar Helena Reyes-Gopar Helena Reyes-Gopar Keila Adonai Pérez-Fuentes Matthew L. Bendall Enrique Hernández-Lemus Enrique Hernández-Lemus Integration of chromosome conformation and gene expression networks reveals regulatory mechanisms in triple negative breast cancer Frontiers in Cell and Developmental Biology triple negative breast cancer chromosome conformation capture hi-c complex networks regulatory genomics |
| title | Integration of chromosome conformation and gene expression networks reveals regulatory mechanisms in triple negative breast cancer |
| title_full | Integration of chromosome conformation and gene expression networks reveals regulatory mechanisms in triple negative breast cancer |
| title_fullStr | Integration of chromosome conformation and gene expression networks reveals regulatory mechanisms in triple negative breast cancer |
| title_full_unstemmed | Integration of chromosome conformation and gene expression networks reveals regulatory mechanisms in triple negative breast cancer |
| title_short | Integration of chromosome conformation and gene expression networks reveals regulatory mechanisms in triple negative breast cancer |
| title_sort | integration of chromosome conformation and gene expression networks reveals regulatory mechanisms in triple negative breast cancer |
| topic | triple negative breast cancer chromosome conformation capture hi-c complex networks regulatory genomics |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1597245/full |
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