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 di...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,sequencebased 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 confrm 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.展开更多
基金supported by a grant from the National Natural Science Foundation of China(62172078)the Science Fund for Distinguished Young Scholars of Sichuan Province(20JCQN0262)+1 种基金supported by an Singapore Ministry of Education Tier I(grant R86/21)awarded to Melissa J.Fullwoodsupported by the China Scholarship Council to visit Nanyang Technological University.
文摘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,sequencebased 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 confrm 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.
