宋添添,崔庆华

• 1:中国人民解放军302医院营养科
• 2:北京大学系统生物医学研究所
• 3:北京大学基础医学院

摘要(Abstract)：

癌症、心血管疾病等复杂疾病的发生发展不是由单一遗传因素引起的,而是受多遗传因素的影响;除了遗传因素,还受很多环境因素的影响,是多个遗传因素和多个环境因素相互作用的结果。因此,本质上,复杂疾病是一种"系统"病,关于其预防、诊断和治疗以及对其的理解亦需要以"系统"的观点和方法来研究。近年来,高通量生物医学技术的迅猛发展为系统生物学的兴起奠定了数据基础,复杂网络理论以及信息学理论的发展亦为系统生物学的发展提供了坚实的方法学基础。近年来,系统生物学在医学研究中得到了广泛的应用,发挥着越来越重要的作用。本文将介绍系统生物学在理解、诊断和治疗疾病中的研究进展。

关键词(KeyWords)： 系统生物学;医学研究;应用;研究进展

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 宋添添,崔庆华

参考文献(References)：

• [1]Weiner N.Cybernetics:or Control and Communication in the animal and the machine[M].MIT Press,Cambridge,MA,1948.
• [2]Kitano H(2002)Systems biology:a brief overview[J].Science,295(5560):1662-1664.
• [3]Barabási A.L,Gulbahce N,Loscalzo J.Network medicine:a network-based approach to human disease[J].Nat Rev Genet,2011,12(1):56-68.
• [4]Macilwain C.Systems biology:evolving in to the mainstream[J].Cell,2011,144(6):839-841.
• [5]Stelzl U,Worm U,Lalowski M,et al.A human protein-protein interaction network:a resource for annotating the proteome[J].Cell,2005,122(6):957-968.
• [6]Cui Q,Yu Z,Purisima EO,et al.Principles of microRNA regulation of a human cellular signaling network[J].Mol Syst Biol,2006,2:46.
• [7]Duarte NC,Becker SA,Jamshidi N,et al.Global reconstruction of the human metabolic network based on genomic and bibliomic data[J].Proc Natl Acad Sci USA,2007,104(6):1777-1782.
• [8]Goh KI,Cusick ME,Valle D,et al.The human disease network[J].Proc Natl Acad Sci USA,2007,104(21):8685-8690.
• [9]Yildirim MA,Goh KI,Cusick ME,et al.Drug-targetnetwork[J].Nat Biotechnol,2007,25(10):1119-1126.
• [10]Najafabadi HS,Salavati R.Sequence-based prediction of protein-protein interactions by means of codon usage[J].Genome biology,2008,9(5):R87.
• [11]Zhang QC,Petrey D,Deng L,et al.Structure-based prediction of protein-protein interactions on a genome-wide scale[J].Nature,2012,490(7421):556-560.
• [12]Cui Q,Ma Y,Jaramillo M,et al.A map of human cancer signaling[J].Mol Syst Biol,2007,3:152.
• [13]Ma'ayan A,Jenkins SL,Neves S,et al.Formation of regulatory patterns during signal propagation in a Mammalian cellular network[J].Science,2005,309(5737):1078-1083.
• [14]Lu M.,Zhang Q,Deng M,et al.An analysis of human microRNA and disease associations[J].PLoS One,2008,3(10):e3420.
• [15]Wang D,Wang J,Lu M,et al.Inferring the human microRNA functional similarity and functional network based on microRNA-associated diseases[J].Bioinformatics,2010,26(13):1644-1650.
• [16]Zhu J,Jambhekar A,Sarver A.et al.A Bayesian network driven approach to model the transcriptional response to nitric oxide in Saccharomyces cerevisiae[J].PLoS One,2006,1:e94.
• [17]Wang J,Lu M,Qiu C.et al.TransmiR:a transcription factor-microRNA regulation database[J].Nucleic Acids Res,38,2010,38(Database issue):D119-122.
• [18]Yang JH,Li JH,Jiang S,et al.ChIPBase:a database for decoding the transcriptional regulation of long non-coding RNA and microRNA genes from ChIP-Seq data[J].Nucleic Acids Res,2013,41(Database issue):D177-187.
• [19]Qiu C,Wang J,Yao P,et al.microRNA evolution in a human transcription factor and microRNA regulatory network[J].BMC systems biology,2010,4:90.
• [20]Lewis BP,Burge CB,Bartel DP.Conserved seed pairing,often flanked by adenosines,indicates that thousands of human genes are microRNA targets[J].Cell,2005,120(1):15-20.
• [21]Krek A,Grün D,Poy MN,et al.Combinatorial microRNA target predictions[J].Nature genetics,2005,37(5):495-500.
• [22]Vergoulis T,Vlachos IS,Alexiou P,et al.TarBase6.0:capturing the exponential growth of miRNA targets with experimental support[J].Nucleic Acids Res,2012,40(Database issue):D222-229.
• [23]Horvath S,Zhang B,Carlson M,et al.Analysis of oncogenic signaling networks in glioblastoma identifies ASPM as a molecular target[J].Proc Natl Acad Sci USA,2006,103(46):17402-17407.
• [24]Qiu C,Chen G,Cui Q.Towards the understanding of microRNA and environmental factor interactions and their relationships to human diseases[J].Sci Rep,2012,2:318.
• [25]Campillos M,Kuhn M,Gavin AC,et al.Drug target identification using side-effect similarity[J].Science,2008,321(5886):263-266.
• [26]Costanzo M,Baryshnikova A,Bellay J,et al.The genetic landscape of a cell[J].Science,2010,327(5964):425-431.
• [27]Fraser HB,Hirsh AE,Steinmetz LM,et al.Evolutionaryrate in the protein interaction network[J].Science,2002,296(5568):750-752.
• [28]Jeong H,Mason SP,Barabasi AL,et al.Lethality and centrality in protein networks[J].Nature,2001,411(6833):41-42.
• [29]Cui Q,Purisima EO,Wang E.Protein evolution on a human signaling network[J].BMC systems biology,2009,3:21.
• [30]Guimera R,Amaral LA.Cartography of complex networks:modules and universal roles[J].J Stat Mech,2005,(PO2001):nihpa35573.
• [31]Milo R,Shen-Orr S,Itzkovitz S,et al.Network motifs:simple building blocks of complex networks[J].Science,2002,298(5594):824-827.
• [32]Watts DJ,Strogatz SH.Collective dynamics of'small-world'networks[J].Nature,1998,393(6684):440-442.
• [33]Barabasi AL,Albert R.Emergence of scaling in random networks[J].Science,1999,286(5439):509-512.
• [34]Greenman C,Stephens P,Smith R,et al.Patterns of somatic mutation in human cancer genomes[J].Nature,2007,446(7132):153-158.
• [35]Kaiser J.Cancer.First pass at cancer genome reveals complex landscape[J].Science,2006,313(5792):1370.
• [36]Sj blom T,Jones S,Wood LD,et al.The consensus coding sequences of human breast and colorectal cancers[J].Science,2006,314(5797):268-274.
• [37]Chng WJ.Limits to the Human Cancer Genome Project?[J].Science,2007,315(5813):762,author reply764-765.
• [38]Loeb LA,Bielas JH.Limits to the Human Cancer Genome Project?[J].Science,2007,315(5813):762,author reply764-765.
• [39]Strauss BS.Limits to the Human Cancer Genome Project?[J].Science,2007,315(5813):762-764,author reply764-765.
• [40]Cao L,Liu X,Lin EJ,et al.Environmental and genetic activation of a brain-adipocyte BDNF/leptin axis causes cancer remission and inhibition[J].Cell,2010,142(1):52-64.
• [41]Adie EA,Adams RR,Evans KL,et al.Speeding disease gene discovery by sequence based candidate prioritization[J].BMC Bioinformatics,2005,6:55.
• [42]van Driel MA,Cuelenaere K,Kemmeren PP,et al.A new web-based data mining tool for the identification of candidate genes for human genetic disorders[J].Eur J of Hum Genet,2003,11(1):57-63.
• [43]Oti M,Brunner HG.The modular nature of genetic diseases[J].Clinical genetics,2007,71(1):1-11.
• [44]Aerts S,Lambrechts D,Maity S,et al.Gene prioritization through genomic data fusion[J].Nat Biotechnol,2006,24(5):537-544.
• [45]Franke L,van Bakel H,Fokkens L,et al.Reconstruction of a functional human gene network,with an application for prioritizing positional candidate genes[J].Am J Hum Genet,2006,78(6):1011-1025.
• [46]Oti M,Snel B,Huynen MA,et al.Predicting disease genes using protein-protein interactions[J].J Med Genet,2006,43(8):691-698.
• [47]Wu X,Jiang R,Zhang MQ,et al.Network-based global inference of human disease genes[J].Mol Syst Biol,2008,4:189.
• [48]Ideker,T.and Sharan,R.Protein networks in disease[J].Genome Res,2008,18(4):644-652.
• [49]Lim J,Hao T,Shaw C,et al.A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration[J].Cell,2006,125(4):801-814.
• [50]Lin J,Gan CM,Zhang X,et al.A multidimensional analysis of genes mutated in breast and colorectal cancers[J].Genome Res,2007,17(9):1304-1318.
• [51]Ghazalpour A,Doss S,Zhang B,et al.Integrating genetic and network analysis to characterize genes related to mouse weight[J].PLoS Genet,2006,2(8):e130.
• [52]Liu B,Jiang T,Ma S,et al.Exploring candidate genes for human brain diseases from a brain-specific gene network[J].Biochem Biophys Res Commun,2006,349(4):1308-1314.
• [53]Wang J,Huang Q,Liu ZP,et al.NOA:a novel Network Ontology Analysis method[J].Nucleic Acids Res,2011,39(13):e87.
• [54]Tuck DP,Kluger HM,Kluger Y.Characterizing disease states from topological properties of transcriptional regulatory networks[J].BMC Bioinformatics,2006,7:236.
• [55]Ma X,Lee H,Wang L,et al.CGI:a new approach for prioritizing genes by combining gene expression and protein-protein interaction data[J].Bioinformatics,2007,23(2):215-221.
• [56]Pujana MA,Han JD,Starita LM,et al.Network modeling links breast cancer susceptibility and centrosome dysfunction[J].Nat Genet,2007,39(11):1338-1349.
• [57]Hopkins AL.Network pharmacology:the next paradigm in drug discovery[J].Nat Chem Biol,2008,4(11):682-690.
• [58]Wang J,Li ZX,Qiu CX,et al.The relationship between rational drug design and drug side effects[J].Brief Bioinform,2012,13(3):377-382.
• [59]Keiser MJ,Setola V,Irwin JJ,et al.Predicting new molecular targets for known drugs[J].Nature,2009,462(7270):175-181.