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厦门大学生物信息学辅助药物开发研究组

Bioinfmatics-Aided Drug Discovery Group, Xiamen University

近年来,课题组的研究重点集中于两个方面:(1)从系统的角度,利用机器学习和网络分析等技术,开展对小分子药物和天然产物的药理、药代动力学,尤其是药毒(药物不良反应)的分子机制研究; 搭建以小分子-大分子相互作用为基础,整合分子对接和数据挖掘等各种技术,开发系列基础关联数据库,构建药物高通量设计和筛选工作流和平台。 (2)开发基于生物芯片、RNA-seq等高通量实验数据分析的新方法和新应用;开展头索动物文昌鱼动物模式化中的理论计算及相关分子机制研究。

药物信息学与药物设计

ADReCS
药物不良反应层级分类系统术语库(Adverse Drug Reaction Classification System, ADReCS)是一个药物不良反应标准化及层级分类系统。该系统收集了现有国际上小分子药物已报道的药物不良反应信息,对其标准化,并建立相应的ADRs关系层级。
ADRAlert
药物不良反应警戒器(Adverse Drug Reaction Alert, ADRAlert)是一个在线的临床药物不良反应评估平台。该平台构建于一个全基因组尺度的药物-基因-药物不良反应关联网络,通过对药物调控基因表达的机器学习,实现大规模快速量化评估药物潜在的不良反应。与此同时,以反向思路探索ADR发生的底层分子机制。
ADReCS-Target
药物不良反应层级分类系统靶点库(ADReCS-Target)是一个用于药物安全性研究的综合靶点数据库。通过提供综合的信息,阐明由药物和蛋白、基因和遗传变异相互作用而引起的药物不良反应。
ADMETNet
药代动力学及毒理学网络化数据库(Absorption, Distribution, Metabolism, Exctretion and Toxicity Network Database, ADMETNet)是整合了药物进入生物体内后吸收(Absorption)、分布(Distribution)、生物转化(Metabolism)和外排(Exctretion)四个阶段以及产生毒性的相关信息,以分子网络图的形式展示,内容涉及主要的药物代谢酶、代谢产物、转运蛋白、作用靶点以及药物毒性相关蛋白及各阶段涉及的组织、器官或细胞等。

生物信息学与系统生物学

IncDNA
文昌鱼胚胎是开展脊椎动物在进化过程中器官胚胎发育分子机制研究的理想模型。但不可否认的是,目前的文昌鱼基因组不足以用来支持开展高质量的转录组学分析。因此,我们整合了异源RNA-seq数据和EST数据组装出佛罗里达文昌鱼整合Transcript库(Integrative transcript library-Branchiostoma floridae, IncDNA-BF,并以Transcript库作为参考,开展转录组学分析,进而系统研究佛罗里达文昌鱼动态的基因表达图谱。
CircleRNA
环状RNA(circRNA)是一类特殊的非编码RNA分子(在活体中有时也有表达),也是近年内RNA领域最新的研究热点。与传统的线性RNA(linear RNA,含5’和3’末端)不同,circRNA分子呈封闭环状结构,不受RNA外切酶影响,表达更稳定,不易降解。在功能上,近年的研究表明,circRNA分子富含microRNA(miRNA)结合位点,在细胞中起到miRNA海绵( miRNA sponge)的作用,进而解除miRNA对其靶基因的抑制作用,升高靶基因的表达水平。通过与疾病关联的miRNA相互作用, circRNA在疾病中发挥着重要的调控作用
PaGeFinder
模式基因发现器(Pattern Gene Finder, PaGeFinder)是一个在线的交互式基因表达谱分析系统。该系统能嵌入了特异分析等4个统计参数,能定量发现用户提交的系列基因表达谱(无论来源于基因芯片、新一代测序NGS或SAGE等高通量技术)中可能存在的模式基因(包括特异表达基因、选择表达基因、抑制基因和管家基因等)。这是国际上首个公开的、能定量描述和发现模式基因的系统。
PaGenBase
模式基因数据库(Pattern Gene Database, PaGenBase)是一个涉及11个物种,1,004个样本,123,000个基因表达谱及文献信息的模式基因数据库。它包含了四类模式基因,分别是特异性基因,选择性基因,看家基因及抑制基因,不仅组织相关的,还包含细胞类型相关及发育阶段相关的模式基因。

Publication List

  1. Liu K, Ding RF, Xu H, et al. Broad-Spectrum Profiling of Drug Safety via Learning Complex Network. Clin Pharmacol Ther. 2020;107(6):1373-1382. doi:10.1002/cpt.1750

  2. Huang LH, He QS, Liu K, Cheng J, Zhong MD, Chen LS, Yao LX, Ji ZL*. ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Research. 2018 Jan; 46: D911-17.

  3. Liu Y, Li YB, Gao X, Yu YF, Liu XX, Ji ZL*, Ma Y, Li YM, Zhao YF*. Evolutionary relationships between seryl-histidine dipeptide and modern serine proteases from the analysis based on mass spectrometry and bioinformatics. Amino Acids. 2017 Oct 25. doi: 10.1007/s00726-017-2487-1.

  4. Tong ML, Zhao Q, Liu LL, Zhu XZ, Gao K, Zhang HL, Lin LR, Niu JJ*, Ji ZL*, Yang TC*. Whole genome sequence of the Treponema pallidum subsp. pallidum strain Amoy: An Asian isolate highly similar to SS14. PLoS One. 2017 Aug 7;12(8): e0182768. doi: 10.1371/journal.pone.0182768. eCollection 2017.

  5. Xu Q, Liu K, Lin X, Qin Y, Chen L, Cheng J, Zhong M, He Q, Li Y, Wang T, Pan J, Peng M, Yao L, Ji Z*. ADMETNet: The knowledge base of pharmacokinetics and toxicology network. Journal of Genetics & Genomics. 2017 May 20;44(5):273-276.

  6. Wei L, Xing P, Shi G, Ji ZL*, Zou Q*. Fast prediction of protein methylation sites using a sequence-based feature selection technique. IEEE/ACM Transactions on Computational Biology and Bioinformatics. 2017 Feb 16. doi: 10.1109/TCBB.2017.2670558.

  7. Zhang J, Wang S, Jiang B, Huang L, Ji Z, Li X, Zhou H, Han A, Chen A, Wu Y, Ma H, Zhao W, Zhao Q, Xie C, Sun X, Zhou Y, Huang H, Suleman M, Lin F, Zhou L, Tian F, Jin M, Cai Y, Zhang N, Li Q*. c-Src phosphorylation and activation of hexokinase promotes tumorigenesis and metastasis. Nature Communications. 2017 Jan 5; 8:13732. doi: 10.1038/ncomms13732.

  8. Fan F, He Z, Kong LL, Chen Q, Yuan Q, Zhang S, Ye J, Liu H, Sun X, Geng J, Yuan L, Hong L, Xiao C, Zhang W, Sun X, Li Y, Wang P, Huang L, Wu X, Ji Z, Wu Q, Xia NS, Gray NS, Chen L, Yun CH, Deng X, Zhou D*. Pharmacological targeting of kinases MST1 and MST2 augments tissue repair and regeneration. Science Translational Medicine. 2016 Aug 17;8(352):352ra108. doi: 10.1126/scitranslmed.aaf2304.

  9. Qin Y, Pan J, Cai M, Yao L, Ji Z*. Pattern Genes Suggest Functional Connectivity of Organs. Sci Rep. 2016 May 26; 6: 26501. doi: 10.1038/srep26501.

  10. Chen L, Zhang YH, Zou Q, Chu C, Ji Z*. Analysis of the chemical toxicity effects using the enrichment of Gene Ontology terms and KEGG pathways. Biochim Biophys Acta. 2016 Nov;1860(11 Pt B):2619-26. doi: 10.1016/j.bbagen.2016.05.015.

  11. Shi S, Liu K, Chen Y, Zhang S, Lin J, Gong C, Jin Q, Yang XJ, Chen R, Ji Z*, Han A*. Competitive inhibition of lysine acetyltransferase 2B by a small motif of the adenoviral oncoprotein E1A. Journal of Biological Chemistry. 2016 May 2. pii: jbc.M115.697300.

  12. He C, Jiang S, Jin H, Chen S, Lin G, Yao H, Wang X, Mi P, Ji Z, Lin Y, Lin Z, Liu G*. Mitochondrial electron transport chain identified as a novel molecular target of SPIO nanoparticles mediated cancer-specific cytotoxicity. Biomaterials. 2016 Mar; 83: 102-14. doi: 10.1016/j.biomaterials.2016.01.010.

  13. Zhang ZF, Ma PF, Jing Y, Yan Y, Cai MC, Zhang MY, Zhang SZ, Peng HX, Ji ZL, Di W, Gu ZY, Gao WQ, Zhuang GL*. BET Bromodomain Inhibition as a Therapeutic Strategy in Ovarian Cancer by Downregulating FoxM1. Theranostics. 2016; 6(2): 219-230. doi: 10.7150/thno.13178.

  14. Lin S*, Cheng S, Song B, Zhong X, Lin X, Li W, Li L, Zhang Y, Zhang H, Ji Z, Cai M, Zhuang Y, Shi X, Lin L, Wang L, Wang Z, Liu X, Yu S, Zeng P, Hao H, Zou Q, Chen C, Li Y, Wang Y, Xu C, Meng S, Xu X, Wang J, Yang H, Campbell DA, Sturm NR, Dagenais-Bellefeuille S, Morse D. The Symbiodinium kawagutii genome illuminates dinoflagellate gene expression and coral symbiosis. Science. 2015 Nov 6;350(6261):691-4. doi: 10.1126/science.aad0408.

  15. Cui YZ, Xu Q, Luan J, Hu SC, Pan JB, Han JX*, Ji ZL*. MVsCarta: A protein database of matrix vesicles to aid understanding of biomineralization. BioScience Trends. 2015 ;9(3):190-192. doi: 10.5582/ bst.2015.01061.

  16. Cai MC, Xu Q, Pan YJ, Pan W, Ji N, Li YB, Jin HJ, Liu K and Ji ZL*. ADReCS: an ontology database for aiding standardization and hierarchical classification of adverse drug reaction terms. Nucleic Acids Research.,2015 Jan 28;43(Database issue):D907-13.

  17. Xiang YP, Liu K, Cheng XY, Cheng C, Gong F, Pan JB, Ji ZL*. Rapid Assessment of Adverse Drug Reactions by Statistical Solution of Gene Association Network. IEEE Transactions on Computational Biology and Bioinformatics. 2015 Jul-Aug;12(4):844-50. doi: 10.1109/TCBB.2014.2338292.

  18. Zou Q, Mao Y, Hu L, Wu Y, Ji ZL*. miRClassify: An advanced web server for miRNA family classification and annotation. Computers in Biology and Medicine. 2014 Feb; 45: 157-160.

  19. Zhang HP, Pan JB, Zhang C, Ji N, Wang H, Ji ZL*. Network understanding of herb medicine via rapid identification of ingredient-target interactions. Sci Rep. 2014 Jan 16;4:3719. doi: 10.1038/srep03719.

  20. Wang Q, Wei L, Guan X, Wu Y, Zou Q, Ji ZL*. Briefing in family characteristics of microRNAs and their applications in cancer research. Biochim Biophys Acta. 2014 Jan;1844 (1 Pt B): 191-7. doi: 10.1016/j.bbapap.2013.08.002.

  21. Pan JB, Hu SC, Shi D, Cai MC, Li YB, Zou Q, Ji ZL*. PaGenBase: a pattern gene database for the global and dynamic understanding of gene function. PLoS ONE. 2013 Dec 2;8(12):e80747. doi: 10.1371/journal.pone.0080747.

  22. Pan JB, Ji N, Pan W, Hong R, Wang H, Ji ZL*. High-throughput Identification of Off-Targets for the Mechanistic Study of Severe Adverse Drug Reactions Induced by Analgesics. Toxicol Appl Pharmacol. 2014 Jan 1;274(1):24-34 . doi: 10.1016/j.taap.2013.10.017.

  23. Cheng XY, Huang WJ, Hu SC, Zhang HL, Wang H, Zhang JX, Lin HH, Chen YZ, Zou Q, Ji ZL*. A global characterization and identification of multifunctional enzymes. PLoS ONE. 2012;7(6):e38979. doi: 10.1371/journal.pone.0038979.

  24. Pan JB, Hu SC, Wang H, Zou Q, Ji ZL*. PaGeFinder: quantitative identification of spatiotemporal pattern genes. Bioinformatics. 2012 Jun 1;28(11):1544-5.

  25. Huang QS, Xie XL, Liang G, Gong F, Wang Y, Wei XQ, Wang Q, Ji ZL*, Chen QX*. The GH18 Family of Chitinases: Their Domain Architectures, Functions, and Evolutions. Glycobiology 2012 Jan;22(1):23-34.

  26. Han DX, Wang HY, Ji ZL, Hu AF, Zhao YF. Amino Acid Homochirality may be Linked to the Origin of Phosphate-Based Life. Journal of Molecular Evolution. 2010 Jun; 70(6): 572-82.

  27. Xiao SJ, Zhang C, Ji ZL*. TiSGeD: a Database for Tissue-Specific Genes. Bioinformatics. 2010 May 1;26(9):1273-5.

  28. Liu XX, Zhang JX, Ni F, Dong X, Han BC, Han DX, Ji ZL*, Zhao YF*. Genome wide exploration of the origin and evolution of amino acids. BMC Evolutionary Biology 2010, 10:77. (IF: 4.294)

  29. Kumar P, Han BC, Shi Z, Jia J, Wang YP, Zhang YT, Liang L, Liu QF, Ji ZL, Chen YZ. Update of KDBI: Kinetic Data of Bio-molecular Interaction database. Nucleic Acids Res. 2009 Jan;37:D636-41.

  30. Quan Y, JiZL* , Wang X, Tartakoff AM, Tao T*. Evolutionary and Transcriptional Analysis of Karyopherin Superfamily Proteins. Mol Cell Proteomics. 2008 Jul;7(7):1254-69.

  31. Han LY, Ma XH, Lin HH, Jia J, Zhu F, Xue Y, Li ZR, Cao ZW, Ji ZL, Chen YZ. A support vector machines approach for virtual screening of active compounds of single and multiple mechanisms from large libraries at an improved hit-rate and enrichment factor. J Mol Graph Model. 2008 Jun; 26 ( 8 ): 1276-86.

  32. Yap CW, Li H, Ji ZL, Chen YZ. Regression methods for developing QSAR and QSPR models to predict compounds of specific pharmacodynamic, pharmacokinetic and toxicological properties. Mini Rev Med Chem.2007 Nov; 7(11):1097-107.

  33. Li G, Zhang QJ, Ji ZL, Wang YQ. Origin and evolution of vertebrate ABCA genes: A story from Amphioxus. Gene. 2007 Dec 15;405(1-2):88-95 .

  34. Xu JR, Zhang JX, Han BC, Liang L, Ji ZL*. CytoSVM: An Advanced Server for Identification of Cytokine-Receptor Interactions. Nucleic Acids Research 2007 Jul 1; 35: W538-42.

  35. Zhang JX, Huang WJ, Huang WH, Wang Y, Zhao R, Han BC, Liu QF, Chen YZ, Ji ZL*. DITOP: Drug-Induced Toxicity Related Protein Database. Bioinformatics 2007, 23 (13): 1710–1712.

  36. Liang L, Han LY, Cai CZ, Huang WH, Chen YZ*, Ji ZL*. Functional Annotation of ORFs in Viral Genomes from Primary Sequence by Support Vector Machine Approach. Journal of Computational Information Systems,2007; 3 (2): 667-673.

  37. Yao LX, Wu ZC, Ji ZL, Chen YZ, Chen X. Internet resources related to drug action and human response: a review. Appl Bioinformatics. 2006; 5(3):131-9.

  38. 王潇,王玉鹏,全宇,纪志梁,陶涛. 细胞核质转运受体 Importin β家族与转运调控研究进展 . 细胞生物学杂志2006; 28(5): 637-645.

  39. 王怡,曾雅明,杨淑佳,纪志梁*. 生物信息学在药物不良反应研究中的应用. 中国药学杂志 2007; 42 (21): 1605-1609.

  40. Wang YP, Liang L, Han BC, Quan Y, Wang X, Tao T, Ji ZL*. GEPS: Gene Expression Pattern Scanner. Nucleic Acids Research 2006 July; 34: W492-W497.

  41. Ji ZL*, Wang Y, Yu L, Han LY, Zheng CJ and Chen YZ. In silico Search of Putative Adverse Drug Reaction Related Proteins as a Potential Tool for Facilitating Drug Adverse Effect Prediction. Toxicology Letters 2006 July 1; 164 (2): 104-112.

  42. Han LY, Cui J, Lin HH, Ji ZL, Cao ZW, Li YS, and Chen YZ. Recent progresses in the application of machine learning approach for predicting protein functional class independent of sequence similarity. Proteomics 2006 June 21; 6(14): 4023-4037.

  43. Zheng CZ, Han LY, Yap CY, Ji ZL, Cao ZW and Chen YZ. Therapeutic Targets: Progress of Their Exploration and Investigation of Their Characteristics. Pharmacological Reviews 2006 Jun;58(2):259-79.

  44. Ji ZL, Li ZR, Wang JF, Cai CZ, Han LY, Zheng CJ, and Chen YZ. Increasing the Odds of Drug Hit Identification by Screening Against Receptor Homologs? Letters in Drug Design & Discovery 2006 April;3(3):200-204.

  45. Ji ZL, Zhou H, Wang JF, Han LY, Zheng CJ, and Chen YZ. Traditional Chinese Medicine Information Database.Journal of Ethnopharmacology 2006 Feb 20;103 (3):501.

  46. Lin HH, Han LY, Cai CZ, Ji ZL and Chen YZ. Prediction of Transporter Family by Support Vector Machine Approach. Proteins. 2006 Jan 1; 62(1):218-31.

  47. 黄文晖, 纪志梁*. 生物信息学在免疫学上的应用. 细胞与分子免疫学杂志. 2006: 22 (1):129-132.

  48. Ji ZL, Han LY, Zheng CJ, Cao ZW and Chen YZ. Prediction of Putative Adverse Drug Reaction Related Proteins from Primary Sequence By Support Vector Machines. International Journal of Pharmaceutical Medicine 2005; 19(6): 317-322.

  49. Cui J, Han LY, Cai CZ, Zheng CJ, Ji ZL, and Chen YZ. Prediction of Functional Class of Novel Bacterial Proteins without the Use of Sequence Similarity by a Statistical Learning Method. Journal of Molecular Microbiology and Biotechnology 2005;9(2): 86-100.

  50. Zhou H, Zarubin T, Ji ZL, Min Z, Zhu W, Downey JS, Lin S, Han J. Frequency and Distribution of AP-1 Sites in the Human Genome. DNA Research. 2005;12(2):139-50.

  51. Cui JA, Han LY, Lin HH, Tang ZQ, Ji ZL, Cao ZW, Li YX, Chen YZ. Advances in exploration of machine learning methods for predicting functional class and interaction profiles of proteins and peptides irrespective of sequence homology. Current Bioinformatics May 2007, 2(2):95-112.

  52. Cao ZW, Han LY, Zheng CJ, Ji ZL, Chen X, Lin HH and Chen YZ. Computer prediction of drug resistance mutations in proteins. Drug Discovery Today 2005;10 (7):521-529.

  53. Han LY, Cai CZ, Ji ZL, Chen YZ. Prediction of Functional Class of Novel Viral Proteins by a Statistical Learning Method Irrespective of Sequence Similarity. Virology 2005 Jan 5;331(1):136-43.

  54. Han LY, Cai CZ, Ji ZL, Cao ZW, Cui J, Chen YZ. Predicting Functional Family of Novel Enzymes Irrespective of Sequence Similarity: A Statistical Learning Approach. Nucleic Acids Research 2004 Dec 7;32(21):6437-44.

  55. Zheng CJ, Sun LZ, Han LY, Ji ZL, Chen X, and Chen YZ. Drug ADME-Associated Protein Database as a Resource for Facilitating Pharmacogenomics Research. Drug Development Research 2004; 62:134–142.

  56. Cai CZ, Han LY, Ji ZL, Chen YZ. Enzyme Family Classification by Support Vector Machines. Proteins.2004; 55(1):66-76.

  57. Cai CZ, Han LY, Ji ZL, Chen X, Chen YZ. SVM-Prot: Web-Based Support Vector Machine Software for Functional Classification of a Protein from Its Primary Sequence. Nucleic Acids Research 2003; 31 (13): 3692-3697.

  58. Ji ZL, Han LY, Yap CW, Sun LZ, Chen X, and Chen YZ. DART: Drug Adverse Reaction Target Database. Drug Safety 2003; 26 (10): 685-690.

  59. Ji ZL, Sun LZ, Chen X, Zheng CJ, Yao LX, Han LY, Cao ZW, Wang JF, Yeo WK, Cai CZ, and Chen YZ. Internet Resources for Proteins Associated with Drug Therapeutic Effects, Adverse Reactions, and ADME. Drug Discovery Today 2003; 8 (12): 526-529.

  60. Ji ZL, Chen X, Zhen CJ, Yao LX, Han LY, Yeo WK, Chung PC, Puy HS, Tay YT, Muhammad A, and Chen YZ. KDBI: Kinetic Data of Bio-molecular Interactions database. Nucleic Acids Research 2003; 31: 255-257.

  61. Sun LZ, Ji ZL, Chen X, Wang JF, Chen YZ. ADME-AP: a database of ADME associated proteins. Bioinformatics 2002; 18(12): 1699-1700.

  62. Chen X, Ji ZL, Zhi DG, Chen YZ. CLiBE: a database of computed ligand binding energy for ligand-receptor complexes. Journal of Computational Chemistry 2002; 26(6): 661-6.

  63. Sun LZ, Ji ZL, Chen X, Wang JF and Chen YZ. ADME Associated Protein Database. Clinical Pharmacology & Therapeutics 2002; 71: 5.

  64. Chen X, Ji ZL and Chen YZ. TTD: Therapeutic Target Database. Nucleic Acids Research 2002; 30: 412-415.

  65. Moe TK, Ji ZL, Barathi A, Beuerman RW. Differential Expression of Glyceraldehyde-3-phophate dehydrogenase (GAPDH), beta actin and hypoxanthine phosphoribosyltransferase (HPRT) in postnatal rabbit sclera. Current Eye Research 2001; 23 (1): 44-50.

  66. Song KP, Chan TK, Ji ZL and Wong SW. Rapid Identification of Pseudomonas aeruginosa from Ocular isolates by PCR Using Exotoxin A-specific Primers. Molecular and Cellular Probes 2000; 14: 199-204.