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Faculty and Staff

CAS Key Laboratory of Genome

Sciences & Information
CAS Key Laboratory of Genomic and
Precision Medicine
BIG Data Center
ZHANG Zhihua
E-mail:zhangzhihua@big.ac.cn
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.
1. Zhang Hui, Li Feifei, Jia Yan, Xu Bingxiang, Zhang Yiqun, Li Xiaoli, Zhang Zhihua#. 2017.
Characteristic arrangement of nucleosomes is predictive of chromatin interactions at kilobase
resolution. Nucleic acids research doi:10.1093/nar/gkx885.

2. Xu Bingxiang, Ge Hao, Zhang Zhihua#. 2017. An efficient and assumption-free method to

approximate protein level distribution in the two-states gene expression model. Journal of theoretical
biology 433: 1-7.

3. Zhang Zhihua#. 2016. A Key to Genome Maze in 3D. Genomics, proteomics & bioinformatics 14: 4-6.

4. 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.

5. 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.

6. Rongxin Fang, Chengqi Wang, Geir Skogerbo, Zhihua Zhang#. (2015). Functional diversity of
CTCFs is encoded in their binding motifs. BMC Genomics 16: 649.

7. 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.

8. 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.

9. Chengqi Wang, Michael Q Zhang, Zhihua Zhang# (2013) Computational identification of active
enhancers in model organisms. Genomics, Proteomics & Bioinformatics. 11(3):142-50.
10. 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.

11. 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

12. 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.

13. 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 Bioinfomatics 12:155.

14. Zhihua Zhang., Wenfeng Qian and Jianzhi Zhang (2009). Positive selection for elevated gene
expression noise in yeast. Molecular Systems Biology. 5:299.

15. Zhihua Zhang and Jianzhi Zhang (2009). A Big World Inside Small-World Networks. PLoS ONE. 4:
e5686.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

25. 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. LI Jing Assistant Professor
Dr. LI Feifei Assistant Professor
Dr. LIU Junfeng Assistant Professor
JIA Yan Master Engineer
Graduate Students
ZHANG Hui, 2012
TANG Bixia, 2013
LI Xiaoli, 2015
LIU Cong, 2015
XU Bingxiang, 2016
ZHANG Xiao, 2014
BAI Xue, 2015

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