title: TopDom: an efficient and deterministic method for identifying topological domains in genomes.
abstract: Genome-wide proximity ligation assays allow the identification of chromatin contacts at unprecedented resolution. Several studies reveal that mammalian chromosomes are composed of topological domains (TDs) in sub-mega base resolution, which appear to be conserved across cell types and to some extent even between organisms. Identifying topological domains is now an important step toward understanding the structure and functions of spatial genome organization. However, current methods for TD identification demand extensive computational resources, require careful tuning and/or encounter inconsistencies in results. In this work, we propose an efficient and deterministic method, TopDom, to identify TDs, along with a set of statistical methods for evaluating their quality. TopDom is much more efficient than existing methods and depends on just one intuitive parameter, a window size, for which we provide easy-to-implement optimization guidelines. TopDom also identifies more and higher quality TDs than the popular directional index algorithm. The TDs identified by TopDom provide strong support for the cross-tissue TD conservation. Finally, our analysis reveals that the locations of housekeeping genes are closely associated with cross-tissue conserved TDs. The software package and source codes of TopDom are available athttp://zhoulab.usc.edu/TopDom/.
authors.affiliation: Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Hanjun
authors.initials: H
authors.lastname: Shin
authors.affiliation: Key Laboratory of Systems Biomedicine, Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiaotong University, Shanghai 200240, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Dai
authors.affiliation: Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Harianto
authors.initials: H
authors.lastname: Tjong
authors.affiliation: Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Gong
authors.affiliation: Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90033, USA alber@usc.edu.
authors.forename: Frank
authors.initials: F
authors.lastname: Alber
authors.affiliation: Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90033, USA xjzhou@dornsife.usc.edu.
authors.forename: Xianghong Jasmine
authors.initials: XJ
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D044127:Epigenesis, Genetic; D020043:Genes, Essential; D023281:Genomics / Q000379:methods*; D006801:Humans; D051379:Mice; D012984:Software
chemical_list: D002843:Chromatin