PMID- 30591009 OWN - NLM STAT- MEDLINE DCOM- 20190204 LR - 20200225 IS - 1471-2105 (Electronic) IS - 1471-2105 (Linking) VI - 19 IP - Suppl 17 DP - 2018 Dec 28 TI - Reconstructing high-resolution chromosome three-dimensional structures by Hi-C complex networks. PG - 496 LID - 10.1186/s12859-018-2464-z [doi] LID - 496 AB - BACKGROUND: Hi-C data have been widely used to reconstruct chromosomal three-dimensional (3D) structures. One of the key limitations of Hi-C is the unclear relationship between spatial distance and the number of Hi-C contacts. Many methods used a fixed parameter when converting the number of Hi-C contacts to wish distances. However, a single parameter cannot properly explain the relationship between wish distances and genomic distances or the locations of topologically associating domains (TADs). RESULTS: We have addressed one of the key issues of using Hi-C data, that is, the unclear relationship between spatial distances and the number of Hi-C contacts, which is crucial to understand significant biological functions, such as the enhancer-promoter interactions. Specifically, we developed a new method to infer this converting parameter and pairwise Euclidean distances based on the topology of the Hi-C complex network (HiCNet). The inferred distances were modeled by clustering coefficient and multiple other types of constraints. We found that our inferred distances between bead-pairs within the same TAD were apparently smaller than those distances between bead-pairs from different TADs. Our inferred distances had a higher correlation with fluorescence in situ hybridization (FISH) data, fitted the localization patterns of Xist transcripts on DNA, and better matched 156 pairs of protein-enabled long-range chromatin interactions detected by ChIA-PET. Using the inferred distances and another round of optimization, we further reconstructed 40 kb high-resolution 3D chromosomal structures of mouse male ES cells. The high-resolution structures successfully illustrate TADs and DNA loops (peaks in Hi-C contact heatmaps) that usually indicate enhancer-promoter interactions. CONCLUSIONS: We developed a novel method to infer the wish distances between DNA bead-pairs from Hi-C contacts. High-resolution 3D structures of chromosomes were built based on the newly-inferred wish distances. This whole process has been implemented as a tool named HiCNet, which is publicly available at http://dna.cs.miami.edu/HiCNet/ . FAU - Liu, Tong AU - Liu T AD - Department of Computer Science, University of Miami, 1365 Memorial Drive, Coral Gables, FL, 33124, USA. FAU - Wang, Zheng AU - Wang Z AD - Department of Computer Science, University of Miami, 1365 Memorial Drive, Coral Gables, FL, 33124, USA. zheng.wang@miami.edu. LA - eng GR - R15 GM120650/GM/NIGMS NIH HHS/United States PT - Journal Article DEP - 20181228 PL - England TA - BMC Bioinformatics JT - BMC bioinformatics JID - 100965194 RN - 0 (RNA, Antisense) RN - 0 (RNA, Long Noncoding) RN - 0 (XIST non-coding RNA) SB - IM MH - Animals MH - Chromatin Immunoprecipitation MH - Chromosomes, Mammalian/*chemistry/*genetics MH - Cluster Analysis MH - In Situ Hybridization, Fluorescence MH - Mice MH - Mouse Embryonic Stem Cells/metabolism MH - RNA, Antisense/metabolism MH - RNA, Long Noncoding/metabolism PMC - PMC6309071 OTO - NOTNLM OT - Chromosomal three-dimensional structure OT - Converting parameter OT - Hi-C complex network OT - Small-world network OT - Topologically associating domain OT - Wish distance COIS- AUTHORS' INFORMATION: Not applicable. ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Not applicable. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/12/29 06:00 MHDA- 2019/02/05 06:00 PMCR- 2018/12/28 CRDT- 2018/12/29 06:00 PHST- 2018/12/29 06:00 [entrez] PHST- 2018/12/29 06:00 [pubmed] PHST- 2019/02/05 06:00 [medline] PHST- 2018/12/28 00:00 [pmc-release] AID - 10.1186/s12859-018-2464-z [pii] AID - 2464 [pii] AID - 10.1186/s12859-018-2464-z [doi] PST - epublish SO - BMC Bioinformatics. 2018 Dec 28;19(Suppl 17):496. doi: 10.1186/s12859-018-2464-z.