张治华 ( ZHANG Zhihua )

本实验室结合计算系统生物学、进化生物学、人工智能（大数据）以及最新的实验技术等手段，研究高等动物基因调控网络的机制和功能。当前的主要研究方向有：

1.开发新的计算及实验技术解析基因组的三维高级结构。

2.转录因子、长非编码RNA、转座子元件等在基因组的三维高级结构的形成、稳定、调控和进化中的作用。

3.以血液系统的发育和疾病为模型，研究三维基因组介导的表观遗传信息的跨代（体细胞，代际）传递和演进机制。

4.基于增强/虚拟现实（AR/VR）和人工智能(深度学习)技术的组学大数据可视化。

本实验室欢迎各种学科背景的学生，包括并不限于物理，数学，统计，计算机，遗传，细胞生化等。

1. 中国科学院A类战略性先导科技专项“种子精准设计与创造”,项目“种子精准设计的变革技术”，课题“颠覆性前沿技术探索”，子课题“整合单细胞影像精准筛选高成活率猪SCNT胚胎”， 2019/9-2022/9,在研，子课题负责人。

2. 国家自然科学基金,重大研究计划集成项目，新型RNA修饰的检测技术开发与功能研究， 2020/1-2022/12,在研，参与。

3. 国家重点研发计划，主动健康和老龄化科技应对重点专项，中国健康长寿大人群多队列的系统研究，长寿人群基因组大数据综合分析平台及健康老龄促进的适宜技术整合、推广和策略, 2018/12-2022/12,在研，参与。

4. 国家自然科学基金, 面上项目，31871331，基于ATAC-seq高精度预测染色质相互作用的新方法和基于增强现实的3D基因组数据可视化, 2019/01-2022/12，在研，项目负责人。

5. 国家自然科学基金, 面上项目，31671342，一种精确捕获真核细胞群体的3D基因组构象及其系综分布的新技术和新算法, 2017/01-2020/12，在研，项目负责人。

研究性论文 * co-first authors

1. Junfeng Liu1*, Ziyang An#, Jianjun Luo, Jing Li, Feifei Li#, Zhihua Zhang#, (2019) Episo: quantitative estimation of RNA 5-methylcytosine at isoform level by high-throughput sequencing of RNA treated with bisulfite, Bioinformatics, 2019 btz900 (Accepted).

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

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

10. 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.

11. 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.

12. 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.

13. 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

14. 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.

15. 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.

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

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

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

25. 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.

26. 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.

27. Zhang Zhihua (2002) On Short Exact Categorie CRM. Journal of Natural Science of Hunan Normal University. Vol.25:13-17. (In Chinese).

综述性论文

1. 刘聪， 张治华# （2019） 基于Hi-C技术识别基因组结构变异及其在肿瘤研究中的应用, 中国科学: 生命科学，2019，已接受.

2. 高晓萌，张治华 #（2019）生物大分子“液液相分离”调控的染色质三维空间结构和功能，遗传，2019，已接受.

3. Feifei Li #, Ziyang An and Zhihua Zhang#, (2019) The dynamic 3D genome in gametogenesis and early embryonic development，Cells, 8(8), 788; https://doi.org/10.3390/cells8080788.

4. Bingxiang Xu, Zhihua Zhang# (2016) Computational inference of physical spatial organization of eukaryotic genomes. Quantitative Biology 4, 302-309.

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

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