Group leader
Dr. ZHANG Zhihua is a principal investigator at Beijing Institute of Genomics (BIG), Chinese Academy of Sciences (CAS). He is an editorial board member of journal Genomics, Proteomics ＆ Bioinformatics since 2012. In 2006, he received his Ph.D. degree from Institute of Biophysics, Chinese Academy of Sciences; 2006-2011, Postdoctoral programs at University of Michigan, The Cold Spring Harbor Laboratory and the University of Texas at Dallas, where he devoted most of his time to studies of computational system biology; In 2011, he joined BIG as a PI for evolutionary and computational systems biology and was selectively supported by the CAS “100-talent Program”. He has undertaken many projects from 863, 973, General Program of National Nature Science Foundation of China (NSFC) etc.
Introduction
ZHANG’s lab combines the methods of computational systems biology with the cutting-edge experimental technologies to study the structure and function of 3D genome (Fig 1). There are four major research interests in our group.
1. 3D Genome. Gene transcription in eukaryotes is tightly regulated by a series of regulatory elements, e.g promoters, enhancers, inhibitors. Many of these regulatory elements located far away from their targeting genes. To determine the interactions between the distal regulatory elements and genes is critical in understanding gene regulatory network (GRN). We are interested in the questions like: a) how to predict target genes of a given distal regulatory element in this complex interaction network; b) how to predict the spatiotemporal expressive pattern by the feature of GRN; c) what is the spatial structure of chromatin fibers in nuclear and its relationship with the GRN functions; d) what is the connection between the 3D genome and variations detected in GWAS studies.
2. Long noncoding RNAs. In the formation of 3D genome structure in nuclear, and the regulatory activity of distal elements, noncoding RNA plays an important role. We are interested in the questions like: a) how lncRNAs interact with chromatin associated proteins in the context of chromatin-chromatin interactions. b) How to predict the targeting genes of a long noncoding RNA ; c) the genesis, process and regulation of enhancer associated RNAs and circularRNAs.
3. The micro-evolution of the gene regulatory network (GRN). We are focusing on how the topology and network dynamics change by the mutation in the process of tumorgenesis, the formation and development of tumor heterogeneity and tumor metastasis and how the changes affect the evolution of tumor in vivo. We anticipate developing a new computational method to identify the genetic or epigenetic variations which play important roles in this process from the point of view of the dynamic evolution of the GRN.
4. Artificial intelligence and biomedical big data. We are focusing on using artificial intelligence to deep mining biomedical big data to understand the relationship between genetic or epigenetic variations and complex diseases, such as cancer and type 2 diabetes.
Selected Publications
* co-first authors. # co-correspondence
1.Yuyang Zhang, Haoyu Wang, Jing Liu, Junlin Li, Qing Zhang#, Bixia Tang#, Zhihua Zhang#. Delta.EPI: a probabilistic voting-based enhancer-promoter interaction prediction platform. Journal of Genetics and Genomics, 2023 (23): S1673-8527.
2.Lei Sun, Gongming Wang, Zhihua Zhang# SimCH: simulation of single-cell RNA sequencing data by modeling cellular heterogeneity at gene expression level，Briefings in Bioinformatics, 2022, bbac590.
3.Qingzhu Yang, Zhihua Zhang# Lattice Simulation-based diffusion modelling of 3D chromatin structure, Computational and Structural Biotechnology Journal, 2022, 20: 3351-3358;
4.Bingxiang Xu#*, Xiaomeng Gao*, Xiaoli Li, Yan Jia, Feifei Li#, Zhihua Zhang#, Cell cycle arrest explained the observed bulk 3D genomic alterations in response to long term heat shock in K562 cells. Genome Research, 2022, 32:1285–1297;
5.Diyan Li*, Mengnan He*, Qianzi Tang*, Shilin Tian*, Jiaman Zhang*, Yan Li, Danyang Wang, Long Jin, Chunyou Ning, Wei Zhu, Silu Hu, Keren Long, Jideng Ma, Jing Liu, Zhihua Zhang#, Mingzhou Li#，Comparative 3D genome architecture in vertebrates，BMC Biology, 2022, 20:99.
6.Bingxiang Xu #, Xiaoli Li, Xiaomeng Gao, Yan Jia, Jing Liu, Feifei Li and Zhihua Zhang#, DeNOPA: decoding nucleosome positions sensitively with sparse ATAC-seq data, Briefings in Bioinformatics, 2022, bbab469.
7.Xiao Li, Guangjie Zeng, Angsheng Li and Zhihua Zhang#, DeTOKI identifies and characterizes the dynamics of chromatin TAD-like domains in a single cell, Genome Biology, 2021, 22, 217.
8.Xue Bai, Feifei Li, Zhihua Zhang#, A hypothetical model of trans-acting R-loops-mediated promoter-enhancer interactions by Alu elements, Journal of Genetics and Genomics, 2021 V48 (11):1007-1019.
9.Bixia Tang, Xiaoxing Li, Guan Li, Dong Tian, Feifei Li, and Zhihua Zhang#, Exploring multiomics data in 3D genomic space using augmented reality based visualization platform Delta.AR. The Innovation, 2021, 2(3),100149.
10.Shengjun Tan, Huijing Ma, Jinbo Wang, Man Wang, Mengxia Wang, Haodong Yin, Yaqiong Zhang, Xinying Zhang, Jieyu Shen, Danyang Wang, Graham L. Banes, Zhihua Zhang, Jianmin Wu, Xun Huang, Hua Chen, Siqin Ge, Chun-Long Chen & Yong E. Zhang. DNA transposons mediate duplications via transposition-independent and -dependent mechanisms in metazoans. Nature Communications, 2021, 12, 4280.
11.Feifei Li*, Danyang Wang*, Ruigao Song*, Chunwei Cao*, Zhihua Zhang*#, Yu Wang, Xiaoli Li, Jiaojiao Huang, Qiang Liu, Naipeng Hou, Bingxiang Xu, Xiao Li, Xiaomeng Gao, Yan Jia, Jianguo Zhao, Yanfang Wang# The asynchronous establishment of chromatin 3D architecture between in vitro fertilized and uniparental preimplantation pig embryos. Genome Biology, 2020, 21:203.
12.Cong Liu, Yiqun Zhang, Xiaoli Li, Yan Jia, Feifei Li#, Jing Li#, Zhihua Zhang# (2020) Evidence of constraint in the 3D genome for trans-splicing in human cells. SCIENCE CHINA Life Sciences, 2020, 63(9):1380-1393.
13.Junfeng Liu*, Ziyang An*, Jianjun Luo, Jing Li, Feifei Li#, Zhihua Zhang#, (2020) Episo: quantitative estimation of RNA 5-methylcytosine at isoform level by high-throughput sequencing of RNA treated with bisulfite, Bioinformatics, 36(7), 2033–2039.
14.Xiao Li*, Ziyang An*, Zhihua Zhang# (2019) Comparison of computational methods for 3D genome analysis at single-cell Hi-C level. Methods, 2019 DOI：10.1016/j.ymeth.2019.08.005.
15.Angsheng Li#, Xianchen Yin, Bingxiang Xu, Danyang Wang, Jimin Han, Yi Wei, Yun Deng, Ying Xiong and Zhihua Zhang# (2018) Decoding Topologically Associating Domains with Ultra-low resolution Hi-C Data by Graph Structural Entropy. Nature Communications, 2018 9:3265.
16.Bixia Tang, Feifei Li, Jing Li, Wenming Zhao#, Zhihua Zhang# (2017) Delta: a new Web-based 3D genome visualization and analysis platform. Bioinformatics, 2017, 34:1409–1410.
17.Hui Zhang*, Feifei Li*, Yan Jia, Bingxiang Xu, Yiqun Zhang, Xiaoli Li, Zhihua Zhang# (2017) Characteristic arrangement of nucleosomes is predictive of chromatin interactions at kilobase resolution. Nucleic Acids Research, 2017 V45, 12739 - 12751.
18.Bingxiang Xu, Hao Ge, Zhihua Zhang# (2017) An efficient and assumption-free method to approximate protein level distribution in the two-states gene expression model. Journal of Theoretical Biology, 2017, 433:1-7.
19.Zhentao Sheng, Lijia Yu, Tianyi Zhang, Xun Pei, Xuan Li, Zhihua Zhang, Wei Du# (2016) ESCRT-0 complex modulates Rbf mutant cell survival by regulating Rhomboid endosomal trafficking and EGFR signaling. Journal of Cell Science, 129: 2075-2084.
20.Xiaoxiao Yun*, Lili Xia*, Bixia Tang, Hui Zhang, Feifei Li, Zhihua Zhang# (2016) 3CDB: A manually curated database of Chromosome Conformation Capture Data. Database, 2016: baw044. doi:10.1093/database/baw044.
21.Rongxin Fang, Chengqi Wang, Geir Skogerbo, Zhihua Zhang# (2015) Functional diversity of CTCFs is encoded in their binding motifs. BMC Genomics, 16: 649.
22.Lina Ma, Peng Cui, Jiang Zhu, Zhihua Zhang and Zhang Zhang (2014) Translational selection in human: more pronounced in housekeeping genes. Biology Direct, 9, 17.
23.Zhihua Zhang# (2014) The Evolution of Heterogeneities Altered by Mutational Robustness, Gene Expression Noise and Bottlenecks in Gene Regulatory Networks. PLoS ONE, 9(12): e116167.
24.Lei Sun, Zhihua Zhang, Timothy L. Bailey, Andrew C. Perkins, Michael R. Tallack, Zhao Xu and Hui Liu (2012) Prediction of novel long non-coding RNAs based on RNA-Seq data of mouse Klf1 knockout study. BMC Bioinformatics, 13:331.
25.Zhihua Zhang, Xiaotu Ma, Michael Q Zhang (2012) Bivalent-Like Chromatin Markers Are Predictive for Transcription Start Site Distribution in Human. PLoS ONE,7(6):e38112
26.Xiaotu Ma, Ashwinikumar Kulkarni, Zhihua Zhang, Zhenyu Xuan and Michael Zhang (2012) A highly efficient and effective motif discovery method for ChIP-seq/ChIP-chip data using positional information. Nucleic Acids Res, 40(7):e50.
27.Zhihua Zhang, Michael Q Zhang (2011) Histone modification profiles are predictive for both protein-coding and microRNA gene’s tissue/cell-type specific expression. BMC Bioinformatics, 12:155.
28.Zhihua Zhang, Wenfeng Qian and Jianzhi Zhang (2009) Positive selection for elevated gene expression noise in yeast. Molecular Systems Biology, 5:299.
29.Zhihua Zhang and Jianzhi Zhang (2009) A Big World Inside Small-World Networks. PLoS ONE, 4: e5686.
30.Zhihua Zhang and Jianzhi Zhang (2008) Accuracy and application of the motif expression decomposition method in dissecting transcriptional regulation. Nucleic Acids Research, 36(10):3185-3193.
31.Zhihua Zhang., Changning Liu., Geir Skogerbo., Xiaopeng Zhu., Hongchao Lu.,Lan Chen., Baochen Shi., Yong Zhang., Tao Wu., Jie Wang and Runsheng Chen (2006) Dynamic Changes in Subgraph Preference Profiles of Crucial Transcription Factors. PLoS Computational Biology, 2(5): e47.
32.Zhihua Zhang., Sun Hong., Yong Zhang., Yi Zhao., Baochen Shi., Shiwei Sun.,Hongchao Lu., Dongbo Bu., Lunjiang Ling and Runsheng Chen (2006). Genome wide Analysis of Mammalian DNA Segment Fusion/Fission. Journal of Theoretical Biolology, 240(2): 200-208.
33.Yong Zhang, Shaojuan Li, Geir Skogerb？, Zhihua Zhang, Xiaopeng Zhu, Zefeng Zhang, Shiwei Sun, Hongchao Lu, Baochen Shi and Runsheng Chen (2006) Phylophenetic properties of metabolic pathway topologies as revealed by global analysis. BMC Bioinformatics, 7, 252.
34.Housheng He., Lun Cai., Geir Skogerbo., Wei Deng., Tao Liu., Xiaopeng Zhu.,Yudong Wang., Dong Jia., Zhihua Zhang., Yong Tao., Haipan Zeng.,Muhammad Nauman Aftab., Yan Cui., Guozhen Liu and Runsheng Chen (2006) Profiling Caenorhabditis elegans non-coding RNA Expression With a Combined Microarray. Nucleic Acids Research, 34(10): 2976–2983.
35.Tao Wu., Jie Wang., Changning Liu., Yong Zhang., Baochen Shi., Xiaopeng Zhu., Zhihua Zhang., Geir Skogerbo., Lan Chen., Hongchao Lu., Yi Zhao and Runsheng Chen (2006) NPInter: the Noncoding RNAs and Protein related biomacromolecules Interaction database. Nucleic Acids Research, 34:D150-D152.
36.Zhang Zhihua., Zhang Yong., Shi Baochen., Deng Wei., Zhao Yi and Chen Runsheng (2004) Detecting Chimeric 5'/3' UTRs with Cross Chromosomal Splicing by Bioinformatics. Chinese Science Bulletin, Vol.49:1051-1054.
37.Zhang Yong., Zhang Zhihua., Ling Lunjiang., Shi Baochen and Chen Runsheng (2004). Conservation analysis of small RNA genes in Escherichia coli. Bioinformatics, 20: 599-603.
38.Wei Deng., Baochen Shi., Xiaoli He., Zhihua Zhang., Jun Xu., Biao Li., JianYang., Lunjiang Ling., Chengping Dai., Boqin Qiang., Yan Shen and Runsheng Chen (2004) Evolution and migration history of Chinese population inferred from Chinese Y-Chromosome evidence. Journal of Human Genetic, 49:339-348.
39.Zhang Zhihua (2002) On Short Exact Categorie CRM. Journal of Natural Science of Hunan Normal University, Vol.25:13-17. (In Chinese).
Group Members
Staff:
Dr. ZHANG Qing, Assistant Professor
Ms. YANG Xiaofang, Assistant Engineer
Graduate Students：
ZHENG Shiqi, 2020
WANG Junmei, 2020
WANG Haoyu, 2020
LI Junlin, 2020
LI Haoxing, 2021
LI Minghao, 2021
CHEN Qiwen, 2021
LUO Yihai, 2021
