A graph neural network-based interpretable framework reveals a novel DNA fragility–associated chromatin structural unit

Abstract Background DNA double-strand breaks (DSBs) are among the most deleterious DNA lesions, and they can cause cancer if improperly repaired. Recent chromosome conformation capture techniques, such as Hi-C, have enabled the identification of relationships between the 3D chromatin structure and D...
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Autor*in:	Yu Sun [verfasserIn] Xiang Xu [verfasserIn] Lin Lin [verfasserIn] Kang Xu [verfasserIn] Yang Zheng [verfasserIn] Chao Ren [verfasserIn] Huan Tao [verfasserIn] Xu Wang [verfasserIn] Huan Zhao [verfasserIn] Weiwei Tu [verfasserIn] Xuemei Bai [verfasserIn] Junting Wang [verfasserIn] Qiya Huang [verfasserIn] Yaru Li [verfasserIn] Hebing Chen [verfasserIn] Hao Li [verfasserIn] Xiaochen Bo [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	DSB 3D chromatin structure Interpretability Graph neural network

Übergeordnetes Werk:	In: Genome Biology - BMC, 2014, 24(2023), 1, Seite 23
Übergeordnetes Werk:	volume:24 ; year:2023 ; number:1 ; pages:23

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s13059-023-02916-x

Katalog-ID:	DOAJ089680758

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520			\|a Abstract Background DNA double-strand breaks (DSBs) are among the most deleterious DNA lesions, and they can cause cancer if improperly repaired. Recent chromosome conformation capture techniques, such as Hi-C, have enabled the identification of relationships between the 3D chromatin structure and DSBs, but little is known about how to explain these relationships, especially from global contact maps, or their contributions to DSB formation. Results Here, we propose a framework that integrates graph neural network (GNN) to unravel the relationship between 3D chromatin structure and DSBs using an advanced interpretable technique GNNExplainer. We identify a new chromatin structural unit named the DNA fragility–associated chromatin interaction network (FaCIN). FaCIN is a bottleneck-like structure, and it helps to reveal a universal form of how the fragility of a piece of DNA might be affected by the whole genome through chromatin interactions. Moreover, we demonstrate that neck interactions in FaCIN can serve as chromatin structural determinants of DSB formation. Conclusions Our study provides a more systematic and refined view enabling a better understanding of the mechanisms of DSB formation under the context of the 3D genome.
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allfields	10.1186/s13059-023-02916-x doi (DE-627)DOAJ089680758 (DE-599)DOAJ49919c5be2a64b1bb7b901c269d79644 DE-627 ger DE-627 rakwb eng QH301-705.5 QH426-470 Yu Sun verfasserin aut A graph neural network-based interpretable framework reveals a novel DNA fragility–associated chromatin structural unit 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background DNA double-strand breaks (DSBs) are among the most deleterious DNA lesions, and they can cause cancer if improperly repaired. Recent chromosome conformation capture techniques, such as Hi-C, have enabled the identification of relationships between the 3D chromatin structure and DSBs, but little is known about how to explain these relationships, especially from global contact maps, or their contributions to DSB formation. Results Here, we propose a framework that integrates graph neural network (GNN) to unravel the relationship between 3D chromatin structure and DSBs using an advanced interpretable technique GNNExplainer. We identify a new chromatin structural unit named the DNA fragility–associated chromatin interaction network (FaCIN). FaCIN is a bottleneck-like structure, and it helps to reveal a universal form of how the fragility of a piece of DNA might be affected by the whole genome through chromatin interactions. Moreover, we demonstrate that neck interactions in FaCIN can serve as chromatin structural determinants of DSB formation. Conclusions Our study provides a more systematic and refined view enabling a better understanding of the mechanisms of DSB formation under the context of the 3D genome. DSB 3D chromatin structure Interpretability Graph neural network Biology (General) Genetics Xiang Xu verfasserin aut Lin Lin verfasserin aut Kang Xu verfasserin aut Yang Zheng verfasserin aut Chao Ren verfasserin aut Huan Tao verfasserin aut Xu Wang verfasserin aut Huan Zhao verfasserin aut Weiwei Tu verfasserin aut Xuemei Bai verfasserin aut Junting Wang verfasserin aut Qiya Huang verfasserin aut Yaru Li verfasserin aut Hebing Chen verfasserin aut Hao Li verfasserin aut Xiaochen Bo verfasserin aut In Genome Biology BMC, 2014 24(2023), 1, Seite 23 (DE-627)326173617 (DE-600)2040529-7 1474760X nnns volume:24 year:2023 number:1 pages:23 https://doi.org/10.1186/s13059-023-02916-x kostenfrei https://doaj.org/article/49919c5be2a64b1bb7b901c269d79644 kostenfrei https://doi.org/10.1186/s13059-023-02916-x kostenfrei https://doaj.org/toc/1474-760X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 1 23
spelling	10.1186/s13059-023-02916-x doi (DE-627)DOAJ089680758 (DE-599)DOAJ49919c5be2a64b1bb7b901c269d79644 DE-627 ger DE-627 rakwb eng QH301-705.5 QH426-470 Yu Sun verfasserin aut A graph neural network-based interpretable framework reveals a novel DNA fragility–associated chromatin structural unit 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background DNA double-strand breaks (DSBs) are among the most deleterious DNA lesions, and they can cause cancer if improperly repaired. Recent chromosome conformation capture techniques, such as Hi-C, have enabled the identification of relationships between the 3D chromatin structure and DSBs, but little is known about how to explain these relationships, especially from global contact maps, or their contributions to DSB formation. Results Here, we propose a framework that integrates graph neural network (GNN) to unravel the relationship between 3D chromatin structure and DSBs using an advanced interpretable technique GNNExplainer. We identify a new chromatin structural unit named the DNA fragility–associated chromatin interaction network (FaCIN). FaCIN is a bottleneck-like structure, and it helps to reveal a universal form of how the fragility of a piece of DNA might be affected by the whole genome through chromatin interactions. Moreover, we demonstrate that neck interactions in FaCIN can serve as chromatin structural determinants of DSB formation. Conclusions Our study provides a more systematic and refined view enabling a better understanding of the mechanisms of DSB formation under the context of the 3D genome. DSB 3D chromatin structure Interpretability Graph neural network Biology (General) Genetics Xiang Xu verfasserin aut Lin Lin verfasserin aut Kang Xu verfasserin aut Yang Zheng verfasserin aut Chao Ren verfasserin aut Huan Tao verfasserin aut Xu Wang verfasserin aut Huan Zhao verfasserin aut Weiwei Tu verfasserin aut Xuemei Bai verfasserin aut Junting Wang verfasserin aut Qiya Huang verfasserin aut Yaru Li verfasserin aut Hebing Chen verfasserin aut Hao Li verfasserin aut Xiaochen Bo verfasserin aut In Genome Biology BMC, 2014 24(2023), 1, Seite 23 (DE-627)326173617 (DE-600)2040529-7 1474760X nnns volume:24 year:2023 number:1 pages:23 https://doi.org/10.1186/s13059-023-02916-x kostenfrei https://doaj.org/article/49919c5be2a64b1bb7b901c269d79644 kostenfrei https://doi.org/10.1186/s13059-023-02916-x kostenfrei https://doaj.org/toc/1474-760X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 1 23
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allfieldsSound	10.1186/s13059-023-02916-x doi (DE-627)DOAJ089680758 (DE-599)DOAJ49919c5be2a64b1bb7b901c269d79644 DE-627 ger DE-627 rakwb eng QH301-705.5 QH426-470 Yu Sun verfasserin aut A graph neural network-based interpretable framework reveals a novel DNA fragility–associated chromatin structural unit 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background DNA double-strand breaks (DSBs) are among the most deleterious DNA lesions, and they can cause cancer if improperly repaired. Recent chromosome conformation capture techniques, such as Hi-C, have enabled the identification of relationships between the 3D chromatin structure and DSBs, but little is known about how to explain these relationships, especially from global contact maps, or their contributions to DSB formation. Results Here, we propose a framework that integrates graph neural network (GNN) to unravel the relationship between 3D chromatin structure and DSBs using an advanced interpretable technique GNNExplainer. We identify a new chromatin structural unit named the DNA fragility–associated chromatin interaction network (FaCIN). FaCIN is a bottleneck-like structure, and it helps to reveal a universal form of how the fragility of a piece of DNA might be affected by the whole genome through chromatin interactions. Moreover, we demonstrate that neck interactions in FaCIN can serve as chromatin structural determinants of DSB formation. Conclusions Our study provides a more systematic and refined view enabling a better understanding of the mechanisms of DSB formation under the context of the 3D genome. DSB 3D chromatin structure Interpretability Graph neural network Biology (General) Genetics Xiang Xu verfasserin aut Lin Lin verfasserin aut Kang Xu verfasserin aut Yang Zheng verfasserin aut Chao Ren verfasserin aut Huan Tao verfasserin aut Xu Wang verfasserin aut Huan Zhao verfasserin aut Weiwei Tu verfasserin aut Xuemei Bai verfasserin aut Junting Wang verfasserin aut Qiya Huang verfasserin aut Yaru Li verfasserin aut Hebing Chen verfasserin aut Hao Li verfasserin aut Xiaochen Bo verfasserin aut In Genome Biology BMC, 2014 24(2023), 1, Seite 23 (DE-627)326173617 (DE-600)2040529-7 1474760X nnns volume:24 year:2023 number:1 pages:23 https://doi.org/10.1186/s13059-023-02916-x kostenfrei https://doaj.org/article/49919c5be2a64b1bb7b901c269d79644 kostenfrei https://doi.org/10.1186/s13059-023-02916-x kostenfrei https://doaj.org/toc/1474-760X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 24 2023 1 23
language	English
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sourceStr	In Genome Biology 24(2023), 1, Seite 23 volume:24 year:2023 number:1 pages:23
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authorswithroles_txt_mv	Yu Sun @@aut@@ Xiang Xu @@aut@@ Lin Lin @@aut@@ Kang Xu @@aut@@ Yang Zheng @@aut@@ Chao Ren @@aut@@ Huan Tao @@aut@@ Xu Wang @@aut@@ Huan Zhao @@aut@@ Weiwei Tu @@aut@@ Xuemei Bai @@aut@@ Junting Wang @@aut@@ Qiya Huang @@aut@@ Yaru Li @@aut@@ Hebing Chen @@aut@@ Hao Li @@aut@@ Xiaochen Bo @@aut@@
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Recent chromosome conformation capture techniques, such as Hi-C, have enabled the identification of relationships between the 3D chromatin structure and DSBs, but little is known about how to explain these relationships, especially from global contact maps, or their contributions to DSB formation. Results Here, we propose a framework that integrates graph neural network (GNN) to unravel the relationship between 3D chromatin structure and DSBs using an advanced interpretable technique GNNExplainer. We identify a new chromatin structural unit named the DNA fragility–associated chromatin interaction network (FaCIN). FaCIN is a bottleneck-like structure, and it helps to reveal a universal form of how the fragility of a piece of DNA might be affected by the whole genome through chromatin interactions. Moreover, we demonstrate that neck interactions in FaCIN can serve as chromatin structural determinants of DSB formation. 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callnumber-first	Q - Science
author	Yu Sun
spellingShingle	Yu Sun misc QH301-705.5 misc QH426-470 misc DSB misc 3D chromatin structure misc Interpretability misc Graph neural network misc Biology (General) misc Genetics A graph neural network-based interpretable framework reveals a novel DNA fragility–associated chromatin structural unit
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topic_title	QH301-705.5 QH426-470 A graph neural network-based interpretable framework reveals a novel DNA fragility–associated chromatin structural unit DSB 3D chromatin structure Interpretability Graph neural network
topic	misc QH301-705.5 misc QH426-470 misc DSB misc 3D chromatin structure misc Interpretability misc Graph neural network misc Biology (General) misc Genetics
topic_unstemmed	misc QH301-705.5 misc QH426-470 misc DSB misc 3D chromatin structure misc Interpretability misc Graph neural network misc Biology (General) misc Genetics
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title	A graph neural network-based interpretable framework reveals a novel DNA fragility–associated chromatin structural unit
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title_full	A graph neural network-based interpretable framework reveals a novel DNA fragility–associated chromatin structural unit
author_sort	Yu Sun
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author_browse	Yu Sun Xiang Xu Lin Lin Kang Xu Yang Zheng Chao Ren Huan Tao Xu Wang Huan Zhao Weiwei Tu Xuemei Bai Junting Wang Qiya Huang Yaru Li Hebing Chen Hao Li Xiaochen Bo
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title_sort	graph neural network-based interpretable framework reveals a novel dna fragility–associated chromatin structural unit
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title_auth	A graph neural network-based interpretable framework reveals a novel DNA fragility–associated chromatin structural unit
abstract	Abstract Background DNA double-strand breaks (DSBs) are among the most deleterious DNA lesions, and they can cause cancer if improperly repaired. Recent chromosome conformation capture techniques, such as Hi-C, have enabled the identification of relationships between the 3D chromatin structure and DSBs, but little is known about how to explain these relationships, especially from global contact maps, or their contributions to DSB formation. Results Here, we propose a framework that integrates graph neural network (GNN) to unravel the relationship between 3D chromatin structure and DSBs using an advanced interpretable technique GNNExplainer. We identify a new chromatin structural unit named the DNA fragility–associated chromatin interaction network (FaCIN). FaCIN is a bottleneck-like structure, and it helps to reveal a universal form of how the fragility of a piece of DNA might be affected by the whole genome through chromatin interactions. Moreover, we demonstrate that neck interactions in FaCIN can serve as chromatin structural determinants of DSB formation. Conclusions Our study provides a more systematic and refined view enabling a better understanding of the mechanisms of DSB formation under the context of the 3D genome.
abstractGer	Abstract Background DNA double-strand breaks (DSBs) are among the most deleterious DNA lesions, and they can cause cancer if improperly repaired. Recent chromosome conformation capture techniques, such as Hi-C, have enabled the identification of relationships between the 3D chromatin structure and DSBs, but little is known about how to explain these relationships, especially from global contact maps, or their contributions to DSB formation. Results Here, we propose a framework that integrates graph neural network (GNN) to unravel the relationship between 3D chromatin structure and DSBs using an advanced interpretable technique GNNExplainer. We identify a new chromatin structural unit named the DNA fragility–associated chromatin interaction network (FaCIN). FaCIN is a bottleneck-like structure, and it helps to reveal a universal form of how the fragility of a piece of DNA might be affected by the whole genome through chromatin interactions. Moreover, we demonstrate that neck interactions in FaCIN can serve as chromatin structural determinants of DSB formation. Conclusions Our study provides a more systematic and refined view enabling a better understanding of the mechanisms of DSB formation under the context of the 3D genome.
abstract_unstemmed	Abstract Background DNA double-strand breaks (DSBs) are among the most deleterious DNA lesions, and they can cause cancer if improperly repaired. Recent chromosome conformation capture techniques, such as Hi-C, have enabled the identification of relationships between the 3D chromatin structure and DSBs, but little is known about how to explain these relationships, especially from global contact maps, or their contributions to DSB formation. Results Here, we propose a framework that integrates graph neural network (GNN) to unravel the relationship between 3D chromatin structure and DSBs using an advanced interpretable technique GNNExplainer. We identify a new chromatin structural unit named the DNA fragility–associated chromatin interaction network (FaCIN). FaCIN is a bottleneck-like structure, and it helps to reveal a universal form of how the fragility of a piece of DNA might be affected by the whole genome through chromatin interactions. Moreover, we demonstrate that neck interactions in FaCIN can serve as chromatin structural determinants of DSB formation. Conclusions Our study provides a more systematic and refined view enabling a better understanding of the mechanisms of DSB formation under the context of the 3D genome.
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title_short	A graph neural network-based interpretable framework reveals a novel DNA fragility–associated chromatin structural unit
url	https://doi.org/10.1186/s13059-023-02916-x https://doaj.org/article/49919c5be2a64b1bb7b901c269d79644 https://doaj.org/toc/1474-760X
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author2	Xiang Xu Lin Lin Kang Xu Yang Zheng Chao Ren Huan Tao Xu Wang Huan Zhao Weiwei Tu Xuemei Bai Junting Wang Qiya Huang Yaru Li Hebing Chen Hao Li Xiaochen Bo
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up_date	2024-07-04T00:11:38.672Z
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Recent chromosome conformation capture techniques, such as Hi-C, have enabled the identification of relationships between the 3D chromatin structure and DSBs, but little is known about how to explain these relationships, especially from global contact maps, or their contributions to DSB formation. Results Here, we propose a framework that integrates graph neural network (GNN) to unravel the relationship between 3D chromatin structure and DSBs using an advanced interpretable technique GNNExplainer. We identify a new chromatin structural unit named the DNA fragility–associated chromatin interaction network (FaCIN). FaCIN is a bottleneck-like structure, and it helps to reveal a universal form of how the fragility of a piece of DNA might be affected by the whole genome through chromatin interactions. Moreover, we demonstrate that neck interactions in FaCIN can serve as chromatin structural determinants of DSB formation. 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Lin</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Kang Xu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Yang Zheng</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Chao Ren</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Huan Tao</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Xu Wang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Huan 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A graph neural network-based interpretable framework reveals a novel DNA fragility–associated chromatin structural unit

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