无标题文档
ÎÞ±êÌâÎĵµ
  
首页 >> 系统生物学研究组 >>
李园园博士介绍(PI)

 

liyuanyuan

 李园园,博士,研究员。

 上海生物信息技术研究中心系统生物学课题组长,上海生物医学研究院生物医学转化应用中心副主任,上海药物转化工程技术研究中心执行主任。上海市生物信息学会理事。

  1996年本科毕业于南开大学微生物系;1999年硕士毕业于中国医学科学院协和医科大学肿瘤研究所分子病毒学实验室;2003年博士毕业于中科院上海生化所。

 作为项目负责人已完成或正在承担国家自然科学基金、973863,科技部传染病重大专项、科技部国际合作项目、上海市科委重大项目等多个科研项目。2006年当选上海市科技启明星。2013年获明治生命科学奖。2015年华夏医学科技奖(第二完成人)。2016年上海市科学技术奖二等奖(第二完成人)。上海市三八红旗手。国务院特殊津贴专家。

 

【主要研究方向】生物信息学,系统生物学,转化医学。

近年来围绕异常调控机制相关驱动因素探索,在生物分子网络模拟分析、肿瘤信息学、功能基因组学、疾病组学等领域开展了一系列知识发现与方法学开发。主要包括以识别驱动因素及其信息传递、交互机制为目的,整合机器学习技术的多组学与计算结构整合、挖掘方法;以肿瘤为代表的复杂系统疾病表型相关的解释性生物标志物识别、预测模型构建、关键基因及其分子网络挖掘、疾病机制探索。在PLoS Computational BiologyBioinformaticsMolecular Systems Biology等国际权威专业期刊上发表论文70余篇。获软件著作权11项。

带领转化医学团队实施基于肿瘤异源移植小鼠模型的肿瘤精准医疗平台建设,搭建了基于肿瘤异源移植小鼠(PDX)模型及其相关数据的肿瘤精准医学研发平台。该平台为患者提供抗肿瘤药物敏感性测试及耐药性预测,指导个性化用药;同时基于PDX模型及数据资源,开展以大数据和人工智能为核心的临床服务和伴随诊断研发,以及抗肿瘤新药研发。该体系的建成对于促进肿瘤个性化治疗策略研发与应用,以及抗肿瘤药物研发具有重大的社会和经济效益。依托此项目,在上海市科委支持下建成了上海药物转化工程技术研究中心,并担任工程中心执行主任,目前已与上海市多家三甲医院、药物研发企业合作开展相关科研及转化医学应用。

带领团队开展基于等温扩增反应的食源性致病微生物快速高效检测试剂方法开发,取得包括引物设计方法、11类致病微生物检测试剂盒以及荧光检测仪在内的一系列研发成果,对食品安全检测领域有重大应用价值。

获26项发明专利授权,1项实用新型专利授权。

 

【主要论文】

Modeling and network analysis:

Li JY, Li YX*, Li YY*. Differential Regulatory Analysis Based on Co-Expression Network in Cancer Research. BioMed Research International. 2016;2016:4241293. doi: 10.1155/2016/4241293.

Yang J, Wu SJ, Yan SY, Peng JW, Wang SN, Wang FY, Song YX, Qi T, Li YX*, Li YY*. DNetDB: The human disease network database based on dysfunctional regulation mechanism. BMC Systems Biology. 2016 May 21;10(1):36. doi: 10.1186/s12918-016-0280-5.

Yang J, Wu SJ, Dai WT, Li YX*, LiYY*. The human disease network in terms of dysfunctional regulatory mechanisms. Biology Direct. 2015, 10: 60. doi:10.1186/s13062-015-0088-z

Yang J, Wu SJ, Li YX*, LiYY*. DSviaDRM: an R package for estimating disease similarity via dysfunctional regulation mechanism. Bioinformatics 2015 Dec 1;31(23):3870-2.

Yu H, Mitra R, Yang J, Li YY, Zhao ZM. Algorithms for network-based identification of differential regulators from transcriptome data: a systematic evaluation. Sci China Life Sc. 2014. doi: 10.1007/s11427-014-4762-7.

Yang J, Yu H, Liu BH, Zhao ZM, Liu L, Li YX*, Li YY*. DCGL v2.0: An R Package for Unveiling Differential Regulation from Differential Co-expression. PLoS ONE. 2013; 8(11): e79729. DOI: 10.1371/journal.pone.0079729

Xu HY, Yu H, Tu K, Shi Q, Wei C, Li YY*, Li YX*. cGRNB: a web server for building combinatorial gene regulatory networks through integrated engineering of seed-matching sequence information and gene expression datasets. BMC Systems Biology. 2013, 7(Suppl 2):S7.

Yu FD, Yang SY, Li YY*, Hu W*. Co-expression networks with Protein-Protein interaction and Transcription regulation in malaria parasite Plasmodium falciparum. Gene. 2013, 518(1): 7-16. DOI: 10.1016/j.gene.2012.11.092. PMID: 23274650.

Kang B, Li Y*, Li Y*. Anti-clustering of circadian gene expression in mouse liver genome. ISB2012

Li RD, Li YY, Lu LY, Ren C, Li YX, Liu L*. An Improved Kinetic Model for Acetone-Butanol-Ethanol Pathway of Clostridium acetobutylicum and Model-Based Perturbation Analysis. BMC Systems Biology. 2011, 5(Suppl 1): S12. (co-first author)

Yu H, Liu BH, Ye ZQ, Li C, Li YX*, Li YY*. Link-based Quantitative Methods to Identify Differentially Coexpressed Genes and Gene Pairs. BMC Bioinformatics. 2011, 12: 315. (Qualified as 'Highly accessed')

Liu BH, Yu H, Tu K, Li C, Li YX*, Li YY*. DCGL: an R package for identifying differentially coexpressed genes and links from gene expression microarray data. Bioinformatics. 2010; 26(20): 2637-8.

Chang X, Liu S, Yu YT, Li YX*, Li YY*. Identifying modules of coexpressed transcript units and their organization of Saccharopolyspora erythraea from time series gene expression profiles. PLoS ONE. 2010; 5(8): e12126.

Chang X, Wang Z, Hao P, Li YY*, Li YX*. Exploring mitochondrial evolution and metabolism organization principles by comparative analysis of metabolic networks. Genomics. 2010; 95: 339-344. (co-corresponding author)

Yu H, Li YY*. Recovering context-specific gene network modules from expression data: a brief review. Frontiers of Biology in China 2009. 4(4): 414-8. doi: 10.1007/s11515-009-0036-3

Tu K, Yu H, Hua YJ, Li YY, Liu L*, Xie L*, Li YX*. Combinatorial network of primary and secondary microRNA-driven regulatory mechanisms. Nucleic Acids Research. 2009. 37(18): 5969-5980.

Luo R, Wei H, Ye L, Wang K, Chen F, Luo L, Liu L, Li Y, Crabbe MJ, Jin L, Li Y*, Zhong Y*. Photosynthetic metabolism of C3 plants shows highly cooperative regulation to maintain function under changing environmental conditions: a systems biological analysis of robustness. Proc Natl Acad Sci USA. 2009. 106(3): 847-52.

Kang B, Li YY, Chang X, Liu L*, Li YX*. Modeling the Effects of Cell Cycle M-phase Transcriptional Inhibition on Circadian Oscillation. PLoS Computational Biology. 2008. 4(3)

Luo R, Liao S, Tao G, Li Y, Li Y*, Luo Q*. Dynamic analysis of optimality in myocardial energy metabolism under normal and ischemic conditions. Molecular Systems Biology. 2006. 2: 2006.0031. Epub 2006 Jun 6.

Wang Z, Zhu X, Chen Y, Li Y, Hou J, Li Y*, Liu L*. Exploring photosynthesis evolution by comparative analysis of metabolic network between chloroplast and cyanobacteria. BMC Genomics. 2006 Apr 30; 7: 100.

  

Comparative and functional genomics:

 Li X, Kong Y, Zhao QY, Li YY, Hao P. De novo assembly of transcriptome from next-generation sequencing data. Quantitative Biology. 2016 June; 4(2): 94-105.

 Liu TLi HDing GWang ZChen YLiu LLi YLi Y. Comparative Genome of GK and Wistar Rats Reveals Genetic Basis of Type 2 Diabetes. PLoS One. 2015 Nov 3;10(11):e0141859.

 Liu Z, Yang J, Xu H, Li C, Wang Z, Li Y, Dong X*, Li Y*. Comparing Computational Methods for Identification of Allele-Specific Expression based on Next Generation Sequencing Data. Genetic Epidemiology.2014, 38(7): 591-598.

 Li YY, Chang X, Yu WB, Li H, Ye ZQ, Yu H, Liu BH, Zhang Y, Zhang SL, Ye BC*, Li YX*. Systems perspectives on erythromycin biosynthesis by comparative genomic and transcriptomic analyses of S. erythraea E3 and NRRL23338 strains. BMC Genomics.2013, 14:523.

 Hu SN, Yu H, Zhang YB, Wu ZL, Yan YC, Li YX, Li YY, Li YP. Splice blocking of zygotic sox31 leads to developmental arrest shortly after Mid-Blastula Transition and induces apoptosis in zebrafish. FEBS letters. 2012, 586: 222-228.

 Yang J, Li YY, Li YX, Ye ZQ. Partition Dataset according to Amino Acid Type Improves the Prediction of Deleterious Non-synonymous SNPs. BBRC. 2012, 419(1): 99-103.

 Chang X, Li Y, Ping J, Xing XB, Sun H, Jia P, Wang C, Li YY*, Li YX*. EcoBrowser: a web-based tool for visualizing transcriptome data of Escherichia coli. BMC Research Notes. 2011, 4: 405. (co-corresponding author)

 Zhong Y, Chang X, Cao XJ, Zhang Y, Zheng HJ, Zhu YZ, Cai CS, Li YY, Zhao GP, Wang SY, Li YX, Zeng R, Li X*, Guo XK*. Comparative Proteogenomic Analysis of the Leptospira interrogans Virulence Attenuated Strain IPAV against the Pathogenic Strain 56601. Cell Research. 2011 Mar 22. doi: 10.1038/cr.2011.46.

 Ye ZQ, Niu S, Yu Y, Yu H, Li RX, Xiao HS, Zeng R, Li YX, Wu JR*, Li YY*. Analyses of Copy Number Variation of GK Rat Reveal New Putative Type 2 Diabetes Susceptibility Loci. PLoS One. 2010. 5(11): e14077.

 Yu H, Tu K, Xie L*, Li YY*. DigOUT: viewing differential expression genes as outliers. Journal of Bioinformatics and Computational Biology 2010. 8(Suppl 1): 161-175.

 Shi YX, Li YY*. Large Number of Phosphotransferase II Genes in the Clostridium beijerinckii NCIMB 8052 Genome and the Study on Their Evolution. BMC Bioinformatics. 2010. 11(Suppl 11): S9.

 Chang X, Cao XJ, Li YY*. Evolutionary rate analysis of differentially expressed proteins between Staphylococcus epidermidis RP62A and ATCC12228. Chinese Science Bulletin. 2010. 55: 3297-3301.

 Ye BC*, Zhang Y, Yu H, Yu WB, Liu BH, Yin BH, Yin CY, Li YY*, Chu J, Zhang SL. Time-Resolved Transcriptome Analysis of Bacillus subtilis Responding to Valine, Glutamate, and Glutamine. PLoS One 2009. 4(9): e7073. doi:10.1371/journal.pone.0007073. (co-corresponding author)

 Yu FD, Li YX, Liu L *, Li YY *. Comparative genomics of human-like Schistosoma japonicum genes indicates a putative mechanism for host-parasite relationship. Genomics. 2008. 91: 152-157.

Yu H, Wang F, Tu K, Xie L, Li YY *, Li YX*. Transcript-level annotation of Affymetrix probesets improves the interpretation of gene expression data. BMC Bioinformatics. 2007. 8:194. (Qualified as 'Highly accessed') (co-corresponding author)

 Yu FD, Kang B, Li YY*, Li YX*. Functional analysis of schistosomes EF-hand domain-containing tegument proteins. Chinese Science Bulletin. 2007. 52(15): 2100-2107. (co-corresponding author)

 Wang L, Yang Z, Li Y, Yu F, Brindley PJ, McManus DP, Wei D, Han Z, Feng Z, Li Y*, Hu W*. Reconstruction and in silico analysis of the MAPK signaling pathways in the human blood fluke, Schistosoma japonicum. FEBS letters. 2006. 580(15): 3677-86. (PMID: 16765950)

Genome organization and regulation:

 Chen YQ, Li YX, Wei J*, Li YY*.Transcriptional regulation and spatial interactions of head-to-head genes. BMC Genomics. 2014, 15: 519.

 Chen YQ, Yu H, Li YX*, Li YY*. Sorting Out Inherent Features of Head-to-Head Gene Pairs by Evolutionary Conservation. BMC Bioinformatics. 2010. 11(Suppl 11): S16.

 Yu H, Yu FD, Zhang GQ, Shen X, Chen YQ, Li YY*, Li YX*. DBH2H: vertebrate head-to-head gene pairs annotated at genomic and post-genomic levels. Database: The Journal of Biological Databases and Curation. 2009. bap006. doi:10.1093/database/bap006. (co-corresponding author)

 Li YY, Yu H, Guo ZM, Guo TQ, Tu K, Li YX*. Systematic analysis of head-to-head gene organization: evolutionary conservation and potential biological relevance. PLoS Computational Biology. 2006. 2(7): e74. Epub 2006 May 15. (PMID: 16839196)

 Li YY, Qin L, Guo ZM, Liu L, Xu H, Hao P, Su J, Shi Y, He WZ*, Li YX*. In silico discovery of human natural antisense transcripts. BMC Bioinformatics. 2006. 7(1): 18. (PMID: 16409644) (Qualified as 'Highly accessed')

  

Protein structure modelling:

 Liu JX, Liu W, Li XL, Dai W*, Li YY*. TGPred: A Tumor Gene Prediction web server for analyzing structural and functional impacts of variants. Journal of Molecular Cell Biology. 2020 Apr 3. mjaa007. doi: 10.1093/jmcb/mjaa007.

 Dai W, Wu A, Ma L, Li YX, Jiang T*, Li YY*. A novel index of proteinprotein interface propensity improves interface residue recognition. BMC Systems Biology. 2016. 10(Suppl 4). doi : 10.1186/s12918-016-0351-7.

Oncology:

 Li Q, Dai W, Liu J, Li YX, Li YY. DysRegSig: an R package for identifying gene dysregulations and building explanatory signatures in cancer. Bioinformatics. 2020 Jul 27. btaa688. doi: 10.1093/bioinformatics/btaa688. 

 Li Q, Dai W, Liu J, Li YX, Li YY. Gene dysregulation analysis builds a mechanistic signature for prognosis and therapeutic benefit in colorectal cancer. Journal of Molecular Cell Biology. 2020 Jul 27. mjaa041. doi: 10.1093/jmcb/mjaa041.

 Dai W, Liu J, Liu B, Li Q, Sang Q, Li YY*. Systematical Analysis of the Cancer Genome Atlas Database Reveals EMCN/MUC15 Combination as a Prognostic Signature for Gastric Cancer. Frontiers in Molecular Biosciences. 2020. 7:19. doi: 10.3389/fmolb.2020.00019

 Li Q, Dai W, Liu J, Li YX, Li YY. DRAP: a toolbox for drug response analysis tailored for preclinical drug testing on patient-derived xenograft models. J Transl Med. 2019 Jan 29;17(1):39. doi: 10.1186/s12967-019-1785-7.

 Zhu MJia NNie YChen J1, Jiang YLv TLi YYao LFeng W. Establishment of Patient-Derived Tumor Xenograft Models of High-Risk Endometrial Cancer. Int J Gynecol Cancer. 2018. 28(9): 1812-1820. doi: 10.1097/IGC.0000000000001365.

 Dai W, Liu J, Li Q, Liu W, Li YX*, Li YY*. A comparison of next generation sequencing analysis methods for cancer xenograft samples. Journal of Genetics and Genomics. 2018. 45 (7): 345-350. doi.org/10.1016/j.jgg.2018.07.001

 Dai W, Li Q, Liu BY, Li YX*, Li YY*. Differential networking meta-analysis of gastric cancer across Asian and American racial groups. BMC Systems Biology. 2018. 12(Suppl 4):51

 Sun W, Shi J, Wu J, Zhang J, Chen H, Li Y, Liu S, Wu Y, Tian Z, Cao X, Li N. A modified HLA-A*0201 restricted CTL epitope from human oncoprotein (hPEBP4) induces more efficient antitumor responses. Cellular & Molecular Immunology. 2017. 14: 1-14.

 Li J, Wu S, Yang L, Li YX, Liu B*, Li YY*. Integrated Differential Regulatory Analysis Reveals a Novel Prognostic 36-gene Signature for Gastric Cancer in Asian Population. Combinatorial Chemistry & High Throughput Screening. 2017. 20:1-8.

 Li Q, Li J, Dai W, Li YX*, Li YY*. Differential regulation analysis reveals dysfunctional regulatory mechanism involving transcription factors and microRNAs in gastric carcinogenesis. Artificial Intelligence in Medicine. 2017. 77: 12-22. doi: http://dx.doi.org/10.1016/j.artmed.2017.02.006

 Wu SJ, Li JY, Cao MS, Yang J, Li YX*, Li YY*. A novel integrated gene coexpression analysis approach reveals a prognostic three-transcription-factor signature for glioma molecular subtypes. BMC Systems Biology. 2016 Aug 26;10 Suppl 3:71. doi: 10.1186/s12918-016-0315-y

 Qi Y, Ooi HS, Wu J, Chen J, Zhang X, Tan S, Yu Q, Li YY, Kang Y, Li H, Xiong Z, Zhu T, Liu B, Shao Z, Zhao X.MALAT1 long ncRNA promotes gastric cancer metastasis by suppressing PCDH10. Oncotarget. 2016 Feb 9. doi: 10.18632/oncotarget.7281.

 Cao MSLiu BYDai WTZhou WXLi YX*, Li YY*. Differential network analysis reveals dysfunctional regulatory networks in gastric carcinogenesis. Am J Cancer Res. 2015 Aug 15;5(9):2605-2625.

 Li H, Zhu Y, Yang X, Li J, Li YY, Zhong ZM, Ding G*, Li Y*. Integrated analysis of transcriptome in cancer patient-derived xenografts. PLoS ONE. 2015. 10(5): e0124780. doi: 10.1371/journal.pone.0124780

 Zhang X, Ma W, Cui J, Yao H, Zhou H, Ge Y, Xiao L, Hu X, Liu BH, Yang J, Li YY, Chen S, Eaves CJ, Wu D, Zhao Y. Regulation of p21 by TWIST2 contributes to its tumor suppressor function in human acute myeloid leukemia. Oncogene. 2014. doi: 10.1038/onc.2014.241.

 Yu H, Lin CC, Li YY, Zhao ZM. Dynamic protein interaction modules in human hepatocellular carcinoma progression. BMC Systems Biology. 2013, 7(Suppl 5):S2.

 Yu H, Tu K, Wang YJ, Mao JZ, Xie L, Li YY*, Li YX*. Combinatorial Network of Transcriptional Regulation and microRNA Regulation in Human Cancer. BMC Systems Biology. 2012, 6: 61.

Signaling transduction:

 Li Y, Wang L, Li S, Guo T, Guo X, Yan P, Chen Y, Wang L, Lu C. P53 protein activates the transcription of human proliferating cell nuclear antigen in response to 4-nitroquinoline N-oxide treatment. International Journal of Biochemistry and Cell Biology. 2005 Feb, 37(2): 416-426.

 Li YY, Wang L, Lu CD. An E2F site in the 5'-promoter region contributes to serum-dependent up-regulation of the human proliferating cell nuclear antigen gene. FEBS Letters. 2003 Jun 5, 544(1-3): 112-118.

Test methods:

 Wang Y, Dai W, Wang Y, Liu J, Liu Z, Li Y, Li X, Hu J, Lü J*. How many cells are enough for single-cell infrared spectroscopy? Chemical Communication. 2020 Apr 4. 56(26): 3773-3776. doi: 10.1039/d0cc00067a

 Jia B, Li X, Liu W, Lu C, Lu X, Ma L, Li YY*, Wei C*. GLAPD: whole genome based LAMP primer design for a set of target genomes. Frontiers in Microbiology. 2019 Dec 13; 10: 2860. doi: 10.3389/fmicb.2019.02860. (Co-corresponding author)

 Zhang Y, Wei Z, Li YY, Chen Y, Shen W, Lu C*. Transcription level of messenger RNA per gene copy determined with dual-spike-in strategy. Analytical Biochemistry. 2009. 394(2): 202-208. (Co-first author)

  

 

 

【已授权发明专利】

RNA和DNA双外参实时定量荧光PCR检测方法及其应用。专利号ZL 2009 1 0049306.5

基于RNA和DNA双外参实时定量PCR的表达校准值的检测方法。专利号 ZL 2013 1 0594531.3

RNA和DNA双外参以及DNA内参实时定量荧光PCR检测方法。专利号ZL 2013 1 0595973.X


【已授权实用新型专利】

一种荧光成像分析系统。专利号ZL2015 2 0237179.2


【软件著作权】

DNetDB (2016SR172969) 基于失调机制的人类疾病间相关关系数据系统

DSviaDRM (2016SR110401) 基于功能失调机制评估疾病间相似性系统

DRA (2014SR125216) 基因表达谱数据的差异调控分析系统

DCGL (2011SR020616) 差异共表达分析

DBH2H (2009SR041122) 脊椎动物头对头基因对在线数据库

FESTIVA (Facility for EST Information Visualization and Analysis) (2005SR08048) EST可视化分析平台

BioEClone (2005SR08053) 电子克隆软件

SMIGA (2005SR08049) 微生物基因组分析平台

CircuitsExplorer (2005SR13024) 基因电路稳定性分析软件