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

作　　者：Fu-Ying Dao Hao Lv Melissa J.Fullwood Hao Lin 

机构地区：[1]Center for Informational Biology,University of Electronic Science and Technology of China,Chengdu 610054,China [2]School of Biological Sciences,Nanyang Technological University,Singapore 639798,Singapore [3]Cancer Science Institute of Singapore,National University of Singapore,14 Medical Dr,Singapore 117599,Singapore [4]Department of Molecular Life Sciences,University of Zurich,Winterthurerstrasse 190,8057 Zurich,Switzerland [5]institute of Molecular and CelBiology,Agency for Science,Technology and Research(A*STAR),Singapore 138673,Singapore

出　　处：《Research》2023年第1期455-468,共14页研究（英文）

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);supported by an Singapore Ministry of Education Tier I(grant R86/21)awarded to Melissa J.Fullwood;supported by the China Scholarship Council to visit Nanyang Technological University.

摘　　要：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.

关 键 词：REPLICATION SIGNATURE ORIGIN 

分 类 号：R394[医药卫生—医学遗传学]