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Accurate Identification of DNA Replication Origin by Fusing Epigenomics and Chromatin Interaction Information

DNA replication initiation is a complex process involving various genetic and epigenomic signatures. The correct identification of replication origins (ORIs) could provide important clues for the study of a variety of diseases caused by replication. Here, we design a computational approach named iOR...

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Autores principales: Dao, Fu-Ying, Lv, Hao, Fullwood, Melissa J., Lin, Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AAAS 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9667886/
https://www.ncbi.nlm.nih.gov/pubmed/36405252
http://dx.doi.org/10.34133/2022/9780293
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author Dao, Fu-Ying
Lv, Hao
Fullwood, Melissa J.
Lin, Hao
author_facet Dao, Fu-Ying
Lv, Hao
Fullwood, Melissa J.
Lin, Hao
author_sort Dao, Fu-Ying
collection PubMed
description DNA replication initiation is a complex process involving various genetic and epigenomic signatures. The correct identification of replication origins (ORIs) could provide important clues for the study of a variety of diseases caused by replication. Here, we design a computational approach named iORI-Epi to recognize ORIs by incorporating epigenome-based features, sequence-based features, and 3D genome-based features. The iORI-Epi displays excellent robustness and generalization ability on both training datasets and independent datasets of K562 cell line. Further experiments confirm that iORI-Epi is highly scalable in other cell lines (MCF7 and HCT116). We also analyze and clarify the regulatory role of epigenomic marks, DNA motifs, and chromatin interaction in DNA replication initiation of eukaryotic genomes. Finally, we discuss gene enrichment pathways from the perspective of ORIs in different replication timing states and heuristically dissect the effect of promoters on replication initiation. Our computational methodology is worth extending to ORI identification in other eukaryotic species.
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spelling pubmed-96678862022-11-17 Accurate Identification of DNA Replication Origin by Fusing Epigenomics and Chromatin Interaction Information Dao, Fu-Ying Lv, Hao Fullwood, Melissa J. Lin, Hao Research (Wash D C) Research Article DNA replication initiation is a complex process involving various genetic and epigenomic signatures. The correct identification of replication origins (ORIs) could provide important clues for the study of a variety of diseases caused by replication. Here, we design a computational approach named iORI-Epi to recognize ORIs by incorporating epigenome-based features, sequence-based features, and 3D genome-based features. The iORI-Epi displays excellent robustness and generalization ability on both training datasets and independent datasets of K562 cell line. Further experiments confirm that iORI-Epi is highly scalable in other cell lines (MCF7 and HCT116). We also analyze and clarify the regulatory role of epigenomic marks, DNA motifs, and chromatin interaction in DNA replication initiation of eukaryotic genomes. Finally, we discuss gene enrichment pathways from the perspective of ORIs in different replication timing states and heuristically dissect the effect of promoters on replication initiation. Our computational methodology is worth extending to ORI identification in other eukaryotic species. AAAS 2022-10-29 /pmc/articles/PMC9667886/ /pubmed/36405252 http://dx.doi.org/10.34133/2022/9780293 Text en Copyright © 2022 Fu-Ying Dao et al. https://creativecommons.org/licenses/by/4.0/Exclusive Licensee Science and Technology Review Publishing House. Distributed under a Creative Commons Attribution License (CC BY 4.0).
spellingShingle Research Article
Dao, Fu-Ying
Lv, Hao
Fullwood, Melissa J.
Lin, Hao
Accurate Identification of DNA Replication Origin by Fusing Epigenomics and Chromatin Interaction Information
title Accurate Identification of DNA Replication Origin by Fusing Epigenomics and Chromatin Interaction Information
title_full Accurate Identification of DNA Replication Origin by Fusing Epigenomics and Chromatin Interaction Information
title_fullStr Accurate Identification of DNA Replication Origin by Fusing Epigenomics and Chromatin Interaction Information
title_full_unstemmed Accurate Identification of DNA Replication Origin by Fusing Epigenomics and Chromatin Interaction Information
title_short Accurate Identification of DNA Replication Origin by Fusing Epigenomics and Chromatin Interaction Information
title_sort accurate identification of dna replication origin by fusing epigenomics and chromatin interaction information
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9667886/
https://www.ncbi.nlm.nih.gov/pubmed/36405252
http://dx.doi.org/10.34133/2022/9780293
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