The long?term objective of the proposed research is to understand the role of genome topological domains as Project Summary the functional and structural units in genome. It also aims to discover the localization preferences of Xist transcripts on chromosome X. Specifically, the proposed research will: 1. Discover the topological and epigenetic preferences of Xist localization on chromosome X by integrating and analyzing the data of multiple histone modifications (ChIP-Seq), CTCF binding (ChIP- Seq), CTCF-CTCF binding (CHIA-PET), Xist localization (RAP), genome topology (Hi-C), and transcribed genes (GRO-seq). 2. Analyze the protein function enrichment of topological domains and regions of chromosome X with various degrees of Xist localization. 3. Implement an ensemble of deep networks to detect boundary of topological domains and predict Xist localization degrees considering two-dimensional or three-dimensional genome topological features and epigenetic properties. 4. Construct the three-dimensional structure of genome topological domains based on normalized Hi-C contacts using an optimization algorithm. 5. Define a novel scoring function to measure both structural signatures and structure-based epigenetic properties of genome topological domain. 6. Cluster topological domains into families based on their structural and epigenetic signatures. 7. Build an online database that interactively visualizes the three-dimensional structure of genome topological domains and dynamically integrates genetic and epigenetic knowledge of the protein-coding genes and non-coding RNA loci existent in each topological domain.
The proposed research tries to understand the roles topological domains play as the functional and structural units of genome and whether there are topological and epigenetic preferences for Xist transcripts to localize on female chromosome X. Chromosome X inactivation and topological domain may have a close relationship to normal gene expression and epigenetic regulations that influence human health.
| Liu, Tong; Wang, Zheng (2018) Reconstructing high-resolution chromosome three-dimensional structures by Hi-C complex networks. BMC Bioinformatics 19:496 |
| Liu, Tong; Wang, Zheng (2018) scHiCNorm: a software package to eliminate systematic biases in single-cell Hi-C data. Bioinformatics 34:1046-1047 |
| Liu, Tong; Wang, Zheng (2018) SOV_refine: A further refined definition of segment overlap score and its significance for protein structure similarity. Source Code Biol Med 13:1 |
| Zhao, Chenguang; Wang, Zheng (2018) GOGO: An improved algorithm to measure the semantic similarity between gene ontology terms. Sci Rep 8:15107 |
| Wang, Zheng; Zhao, Chenguang; Wang, Yiheng et al. (2018) PANDA: Protein function prediction using domain architecture and affinity propagation. Sci Rep 8:3484 |
