转录因子CEBPB在全反式维甲酸诱导急性早幼粒细胞白血病中靶基因的确认（合成生物学在医学中的应用）
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摘要
本研究旨在探索转录因子CEBPB (CCAAT enhancer-binding protein β, CCAAT增强结合蛋白β)在全反式维甲酸(ATRA, All-trans retinoic acid)诱导急性早幼粒细胞白血病(APL, acute promyelocytic leukemia)细胞分化的调控机制。应用染色质免疫沉淀技术(ChIP)和体外筛选相结合的方法进行高通量分析(high throughput assay),确定CEBPB的下游靶基因。一百零六个CEBPB的结合片段从ATRA诱导NB4细胞的基因组(genome)中选出。其中,82个片段在已知或先前预测的基因中找到；其中,随机取出7片段用ChIP-PCR方法进一步确认,最后,确认3个基因(GALM, ITPR2和ORM2)在ARTA诱导NB4细胞中高表达(up-regulated),这表明它们可能是转录因子CEBPB的下游靶基因。该实验结果对揭示ATRA诱导粒细胞分化的机制提供了新的启发。图25幅,表2个,参考文献164篇
This study is to explore the mechanism of transcription factor CEBPB (CCAAT enhancer-binding protein β) in regulation of the acute promyelocytic leukemia (APL) cell differentiation induced by All-trans retinoic acid (ATRA). The method of combining chromatin immunoprecipitation (ChIP) with in vitro selection was applied for high-throughput identification of the CEBPB downstream direct target genes. One Hundred and six CEBPB binding fragments from the genome of the ATRA-treated NB4cells were selected after ChIP. Among them,82were mapped in proximity to the known or previously predicted genes; meanwhile,7were randomly picked up for further confirmation by ChIP-PCR and finally3genes (GALM, ITPR2and ORM2) were found to be specifically up-regulated in ATRA-treated NB4cells, indicating that they might be the down-stream target genes of transcription factor CEBPB. The results provide a new insight into the mechanisms of ATRA-induced granulocytic differentiation.
This study is to explore the mechanism of transcription factor CEBPB (CCAAT enhancer-binding protein β) in regulation of the acute promyelocytic leukemia (APL) cell differentiation induced by All-trans retinoic acid (ATRA). The method of combining chromatin immunoprecipitation (ChIP) with in vitro selection was applied for high-throughput identification of the CEBPB downstream direct target genes. One Hundred and six CEBPB binding fragments from the genome of the ATRA-treated NB4cells were selected after ChIP. Among them,82were mapped in proximity to the known or previously predicted genes; meanwhile,7were randomly picked up for further confirmation by ChIP-PCR and finally3genes (GALM, ITPR2and ORM2) were found to be specifically up-regulated in ATRA-treated NB4cells, indicating that they might be the down-stream target genes of transcription factor CEBPB. The results provide a new insight into the mechanisms of ATRA-induced granulocytic differentiation.
引文
[1]Zheng, P. Z., Wang, K. K., Zhang, Q. Y, Huang, Q. H., Du, Y. Z., Zhang, Q. H., Xiao, D. K., Shen, S. H., Imbeaud, S., Eveno, E., Zhao, C. J., Chen, Y. L., Fan, H. Y, Waxman, S., Auffray, C., Jin, G., Chen, S. J., Chen, Z., and Zhang, J. (2005) Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell diflferentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A 102, 7653-7658.
[2]Duprez, E., Wagner, K., Koch, H., and Tenen, D. G (2003) C/EBPbeta:a major PML-RARA-responsive gene in retinoic acid-induced differentiation of APL cells. Embo J 22,5806-5816.
[3]Hirai, H., Zhang, P., Dayaram, T., Hetherington, C. J., Mizuno, S., Imanishi, J., Akashi, K., and Tenen, D. G (2006) C/EBPbeta is required for 'emergency' granulopoiesis. Nat Immunol 7,732-739.
[4]Weinmann, A. S. (2004) Novel ChlP-based strategies to uncover transcription factor target genes in the immune system. Nat Rev Immunol 4,381-386.
[5]Greenbaum, S., and Zhuang, Y (2002) Identification of E2A target genes in B lymphocyte development by using a gene tagging-based chromatin immunoprecipitation system. Proc Natl Acad Sci U S A 99,15030-15035.
[6]Weinmann, A. S., Bartley, S. M., Zhang, T., Zhang, M. Q., and Farnham, P. J. (2001) Use of chromatin immunoprecipitation to clone novel E2F target promoters. Mol Cell Biol 21,6820-6832.
[7]Weinmann, A. S., and Farnham, P. J. (2002) Identification of unknown target genes of human transcription factors using chromatin immunoprecipitation. Methods 26,37-47.
[8]Hug, B. A., Ahmed, N., Robbins, J. A., and Lazar, M. A. (2004) A chromatin immunoprecipitation screen reveals protein kinase Cbeta as a direct RUNX1 target gene. J Biol Chem 279,825-830.
[9]Hao, B., Miao, X., Li, Y, Zhang, X., Sun, T., Liang, G, Zhao, Y, Zhou, Y, Wang, H., Chen, X., Zhang, L., Tan, W., Wei, Q., Lin, D., and He, F. (2006) A novel T-77C polymorphism in DNA repair gene XRCC1 contributes to diminished promoter activity and increased risk of non-small cell lung cancer. Oncogene 25,3613-3620.
[10]Matsumoto, M., Tanaka, T., Kaisho, T., Sanjo, H., Copeland, N. G, Gilbert, D. J., Jenkins, N. A., and Akira, S. (1999) A novel LPS-inducible C-type lectin is a transcriptional target of NF-IL6 in macrophages. J Immunol 163,5039-5048.
[11]Osada, S., Yamamoto, H., Nishihara, T., and Imagawa, M. (1996) DNA binding specificity of the CCAAT/enhancer-binding protein transcription factor family. J Biol Chem 271,3891-3896.
[12]Hochepied, T., Berger, F. G, Baumann, H., and Libert, C. (2003) Alpha(1)-acid glycoprotein:an acute phase protein with inflammatory and immunomodulating properties. Cytokine Growth Factor Rev 14,25-34.
[13]Theilgaard-Monch, K., Jacobsen, L. C., Rasmussen, T., Niemann, C. U., Udby, L., Borup, R., Gharib, M., Arkwright, P. D., Gombart, A. F., Calafat, J., Porse, B. T., and Borregaard, N. (2005) Highly glycosylated alphal-acid glycoprotein is synthesized in myelocytes, stored in secondary granules, and released by activated neutrophils. J Leukoc Biol 78,462-470.
[14]Berridge, M. J., Bootman, M. D., and Roderick, H. L. (2003) Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 4,517-529.
[15]Sugiyama, T., Yamamoto-Hino, M., Miyawaki, A., Furuichi, T., Mikoshiba, K., and Hasegawa, M. (1994) Subtypes of inositol 1,4,5-trisphosphate receptor in human hematopoietic cell lines:dynamic aspects of their cell-type specific expression. FEBS Lett 349,191-196.
[16]Timson, D. J., and Reece, R. J. (2003) Identification and characterisation of human aldose 1-epimerase. FEBS Lett 543,21-24.
[17]Horak, C. E., Mahajan, M. C., Luscombe, N. M., Gerstein, M., Weissman, S. M., and Snyder, M. (2002) GATA-1 binding sites mapped in the beta-globin locus by using mammalian chIp-chip analysis. Proc Natl Acad Sci U S A 99,2924-2929.
[18]Weinmann, A. S., Yan, P. S., Oberley, M. J., Huang, T. H., and Farnham, P. J. (2002) Isolating human transcription factor targets by coupling chromatin immunoprecipitation and CpG island microarray analysis. Genes Dev 16,235-244.
[19]Cawley, S., Bekiranov, S., Ng, H. H., Kapranov, P., Sekinger, E. A., Kampa, D., Piccolboni, A., Sementchenko, V., Cheng, J., Williams, A. J., Wheeler, R., Wong, B., Drenkow, J., Yamanaka, M., Patel, S., Brubaker, S., Tammana, H., Helt, G, Struhl, K., and Gingeras, T. R. (2004) Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell 116,499-509.
[20]Kim, T. H., Barrera, L. O., Zheng, M., Qu, C., Singer, M. A., Richmond, T. A., Wu, Y, Green, R. D., and Ren, B. (2005) A high-resolution map of active promoters in the human genome. Nature 436,876-880.
[21]Nelson, E. A., Walker, S. R., Alvarez, J. V., and Frank, D. A. (2004) Isolation of unique STAT5 targets by chromatin immunoprecipitation-based gene identification. J Biol Chem 279,54724-54730.
[22]Barski, A., and Frenkel, B. (2004) ChIP Display:novel method for identification of genomic targets of transcription factors. Nucleic Acids Res 32, e104.
[23]Hearnes, J. M., Mays, D. J., Schavolt, K. L., Tang, L., Jiang, X., and Pietenpol, J. A. (2005) Chromatin immunoprecipitation-based screen to identify functional genomic binding sites for sequence-specific transactivators. Mol Cell Biol 25,10148-10158.
[24]Schrem, H., Klempnauer, J., and Borlak, J. (2004) Liver-enriched transcription factors in liver function and development. Part Ⅱ:the C/EBPs and D site-binding protein in cell cycle control, carcinogenesis, circadian gene regulation, liver regeneration, apoptosis, and liver-specific gene regulation. Pharmacol Rev 56,291-330.
[25]Ramji, D. P., and Foka, P. (2002) CCAAT/enhancer-binding proteins:structure, function and regulation. Biochem J 365,561-575.
[26]Friedman, J. R., Larris, B., Le, P. P., Peiris, T. H., Arsenlis, A., Schug, J., Tobias, J. W., Kaestner, K. H., and Greenbaum, L. E. (2004) Orthogonal analysis of C/EBPbeta targets in vivo during liver proliferation. Proc Natl Acad Sci U S A 101,12986-12991.
[27]Yonggang Ke, Luvena L. Ong, William M. Shih, Peng Yin (2012) Three-Dimensional structures self-assembled from DNA bricks. Science 30 November 2012:Vol.338 no.6111 pp.1177-1183 DOI:10.1126/science. 1227268
[28]Editing the Genome:Scientists Unveil New Tools for Rewriting the Code of Life. Science News. July 15,2011
[29]George M. Church, Yuan Gao, Sriram Kosuri. Next-Generation Digital Information Storage in DNA. Published Online August 16 2012. Science 28 September 2012:Vol.337 no.6102 p.1628 DOI:10.1126/science.1226355
[30]Arkin, A. P. & Schaffer, D. V. Network news:innovations in 21st century systems biology. Cell 144,844-849 (2011).
[31]Roy, S. et al. Identification of functional elements and regulatory circuits by Drosophila modENCODE. Science 330,1787-1797 (2010).
[32]Smolke, C. D. & Silver, P. A. Informing biological design by integration of systems and synthetic biology. Cell 144,855-859 (2011).
[33]Jasny, B. R. & Zahn, L. M. Genome-sequencing anniversary. A celebration of the genome, part I. Science 331,546 (2011).
[34]Nielsen, R., Paul, J. S., Albrechtsen, A. & Song, Y. S. Genotype and SNP calling from next-generation sequencing data. Nature Rev. Genet.12,443-451 (2011).
[35]Kosuri, S. et al. Scalable gene synthesis by selective amplification of DNA pools from high-fidelity microchips. Nature Biotech.28,1295-1299 (2010).
[36]Matzas, M. et al. High-fidelity gene synthesis by retrieval of sequence-verified DNA identified using high-throughput pyrosequencing. Nature Biotech.28, 1291-1294 (2010).
[37]Quan, J. et al. Parallel on-chip gene synthesis and application to optimization of protein expression. Nature Biotech.29,449-452 (2011).
[38]Gibson, D. G. et al. Creation of a bacterial cell controlled by a chemically synthesized genome. Science 329,52-56 (2010).
[39]Bedau, M. et al. Life after the synthetic cell. Nature 465,422-424 (2010).
[40]Burrill, D. R. & Silver, P. A. Making cellular memories. Cell 140,13-18 (2010).
[41]Danino, T., Mondragon-Palomino, O., Tsimring, L. & Hasty, J. A synchronized quorum of genetic clocks. Nature 463,326-330 (2010).
[42]Leisner, M., Bleris, L., Lohmueller, J., Xie, Z. & Benenson, Y. Rationally designed logic integration of regulatory signals in mammalian cells. Nature Nanotechnol.5,666-670 (2010).
[43]Toettcher, J. E., Mock, C., Batchelor, E., Loewer, A. & Lahav, G. A synthetic-natural hybrid oscillator in human cells. Proc. Natl Acad. Sci. USA 107,17047-17052(2010).
[44]Xie, Z., Wroblewska, L., Prochazka, L., Weiss, R. & Benenson, Y. Multi-input RNAi-based logic circuit for identification of specific cancer cells. Science 333, 1307-1311(2011).
[45]Nandagopal, N. & Elowitz, M. B. Synthetic biology:integrated gene circuits. Science 333,1244-1248 (2011).
[46]Aubel, D. & Fussenegger, M. Mammalian synthetic biology—from tools to therapies. Bioessays 32,332-345 (2010).
[47]Weber, W. & Fussenegger, M. Synthetic gene networks in mammalian cells. Curr. Opin. Biotechnol.692,235-249 (2010).
[48]Weber, W. & Fussenegger, M. Molecular diversity—the toolbox for synthetic gene switches and networks. Curr. Opin. Chem. Biol.15,414-420 (2011).
[49]Wieland, M. & Fussenegger, M. Ligand-dependent regulatory RNA parts for synthetic biology in eukaryotes. Curr. Opin. Biotechnol.21,760-765 (2010).
[50]Yao, G., Tan, C., West, M., Nevins, J. R. & You, L. Origin of bistability underlying mammalian cell cycle entry. Mol. Syst. Biol.7,485 (2011).
[51]Karlsson, M., Weber, W. & Fussenegger, M. De novo design and construction of an inducible gene expression system in mammalian cells. Methods Enzymol. 497,239-253(2011).
[52]Aubel, D. & Fussenegger, M. Watch the clock-engineering biological systems to be on time. Curr. Opin. Genet. Dev.20,634-643 (2010).
[53]Tigges, M., Denervaud, N., Greber, D., Stelling, J. & Fussenegger, M. A synthetic low-frequency mammalian oscillator. Nucleic Acids Res.38, 2702-2711 (2010).
[54]Khalil, A. S. & Collins, J. J. Synthetic biology:applications come of age. Nature Rev. Genet.11,367-379 (2010).
[55]Kemmer, C. et al. A designer network coordinating bovine artificial insemination by ovulation-triggered release of implanted sperms. J. Control. Release 150,23-29(2011).
[56]Kemmer, C. et al. Self-sufficient control of urate homeostasis in mice by a synthetic circuit. Nature Biotech.28,355-360 (2010).
[57]Ye, H., Daoud-El Baba, M., Peng, R. W. & Fussenegger, M. A synthetic optogenetic transcription device enhances blood-glucose homeostasis in mice. Science 332,1565-1568 (2011).
[58]The first optogenetic device that controls the production of a therapeutic protein in an animal disease model is described in this paper.
[59]Fears, R. & ter Meulen, V. The potential of synthetic biology:a view from the European Academies Science Advisory Council. Nature Rev. Microbiol.9,222 (2011).
[60]Ruder, W. C., Lu, T. & Collins, J. J. Synthetic biology moving into the clinic. Science 333,1248-1252 (2011).
[61]Burbelo, P. D., Ching, K. H., Bush, E. R., Han, B. L. & Iadarola, M. J. Antibody-profiling technologies for studying humoral responses to infectious agents. Expert Rev. Vaccines 9,567-578 (2010).
[62]Chandra, A., Wormser, G P., Marques, A. R., Latov, N. & Alaedini, A. Anti-Borrelia burgdorferi antibody profile in post-Lyme disease syndrome. Clin. Vaccine Immunol.18,767-771 (2011).
[63]Burbelo, P. D. et al. LIPS arrays for simultaneous detection of antibodies against partial and whole proteomes of HCV, HIV and EBV. Mol. Biosyst.7, 1453-1462(2011).
[64]Yang, J. & Reth, M. Oligomeric organization of the B-cell antigen receptor on resting cells. Nature 467,465-469 (2010).
[65]McMichael AJ, Borrow P, Tomaras GD, Goonetilleke N, Haynes BF. The immune response during acute HIV-1 infection:clues for vaccine development. Nat Rev Immunol 2010; 10:11-23.
[66]Kaufmann SH. Future vaccination strategies against tuberculosis:thinking outside the box. Immunity 2010; 33:567-77.
[67]Bambini S, Rappuoli R. The use of genomics in microbial vaccine development. Drug Discov Today 2009; 14:252-60.
[68]Raab D, Graf M, Notka F, Schodl T, Wagner R. The Gene Optimizer Algorithm: using a sliding window approach to cope with the vast sequence space in multiparameter DNA sequence optimization. Syst Synth Biol 2010; 4:215-25.
[69]Maertens B, Spriestersbach A, von Groll U, Roth U, Kubicek J, Gerrits M, et al. Gene optimization mechanisms:a multi-gene study reveals a high success rate of full-length human proteins expressed in Escherichia coli. Protein Sci 2010; 19:1312-26.
[70]Kindsmuller K, Wagner R. Synthetic biology:impact on the design of innovative vaccines. Hum Vaccin.2011 Jun;7(6):658-62. Epub 2011 Jun 1.
[71]Bazhan SI, Karpenko LI, Ilyicheva TN, Belavin PA, Seregin SV, Danilyuk NK, et al. Rational design based synthetic polyepitope DNA vaccine for eliciting HIV-specific CD8+T cell responses. Mol Immunol 2010; 47:1507-15.
[72]Barouch DH, O'Brien KL, Simmons NL, King SL, Abbink P, Maxfield LF, et al. Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys. Nat Med 2010; 16:319-23
[73]Chiarella P, Massi E, De Robertis M, Fazio VM,Signori E. Recent advances in epitope design for immunotherapy of cancer. Recent Pat Anticancer Drug Discov 2009; 4:227-40.
[74]Alexander J, Bilsel P, del Guercio MF, Marinkovic- Petrovic A, Southwood S, Stewart S, et al. Identification of broad binding class I HLA supertype epitopes to provide universal coverage of influenza A virus. Hum Immunol 2010; 71:468-74.
[75]Larsen MV, Lelic A, Parsons R, Nielsen M, Hoof I, Lamberth K, et al. Identification of CD8+T cell epitopes in the West Nile virus polyprotein by everse-immunology using NetCTL. PLoSOne 2010; 5:12697.
[76]Salimi N, Fleri W, Peters B, Sette A. Design and utilization of epitope-based databases and predictive tools. Immunogenetics 2010; 62:185-96.
[77]Tian S, Liu Z, Donahue C, Noh HS, Falo LD Jr, You Z. Transcriptional IL-15-directed in vivo DC targeting DNA vaccine. Gene Ther 2009; 16:1260-70
[78]Bringmann A, Held SA, Heine A, Brossart P, RNA vaccine in cancer treatment. J Biomed Biotechnol 2010,623687
[79]Mueller S, Coleman JR, Papamichail D, Ward CB, Nimnual A, Futcher B, et al. Live attenuated influenza virus vaccines by computer-aided rational design.Nat Biotechnol 2010; 28:723-6.
[80]Gibson DG, Glass JI, Lartigue C, Noskov VN, Chuang RY, Algire MA, et al. Creation of a bacterial cell controlled by a chemically synthesized genome.Science 2010; 329:52-6.
[81]Burbelo PD, Ching KH, Han BL, Klimavicz CM, Iadarola MJ. Synthetic biology for translational research. Am J Transl Res 2010; 2:381-9
[82]Wise de Valdez, M. R. et al. Genetic elimination of dengue vector mosquitoes. Proc. Natl Acad. Sci. USA 108,4772-4775 (2011).
[83]Windbichler, N. et al. A synthetic homing endonuclease-based gene drive system in the human malaria mosquito. Nature 473,212-215 (2011).
[84]Subbaraman, N. Science snipes at Oxitec transgenic-mosquito trial. Nature Biotech.29,9-11 (2011).
[85]Allison, K. R., Brynildsen, M. P. & Collins, J. J. Metabolite-enabled eradication of bacterial persisters by aminoglycosides. Nature 473,216-220 (2011).
[86]Lee, H. H., Molla, M. N., Cantor, C. R. & Collins, J. J. Bacterial charity work leads to population-wide resistance. Nature 467,82-85 (2010).
[87]Kohanski, M. A., DePristo, M. A. & Collins, J. J. Sublethal antibiotic treatment leads to multidrug resistance via radical-induced mutagenesis. Mol. Cell 37, 311-320(2010).
[88]Kohanski, M. A., Dwyer, D. J. & Collins, J. J. How antibiotics kill bacteria: from targets to networks. Nature Rev. Microbiol.8,423-435 (2010).
[89]Forbes, N. S. Engineering the perfect (bacterial) cancer therapy. Nature Rev. Cancer 10,785-794 (2010).
[90]Voelkel, C. et al. Protein transduction from retroviral Gag precursors. Proc. Natl Acad. Sci. USA 107,7805-7810 (2010).
[91]Zhang, F. et al. Efficient construction of sequence-specific TAL effectors for modulating mammalian transcription. Nature Biotech.29,149-153 (2011).
[92]Metzker ML. Sequencing technologies-the next generation. Nat Rev Genet. 2010; 11:31-46.
[93]Mardis ER, et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med.2009; 361:1058-1066.
[94]Pleasance ED, et al. A comprehensive catalogue of somatic mutations from a human cancer genome. Nature.2010; 463:191-196.
[95]Taylor BS, et al. Integrative genomic profiling of human prostate cancer. Cancer Cell.2010;18:11-22.
[96]Lee W, et al. The mutation spectrum revealed by paired genome sequences from a lung cancer patient. Nature.2010; 465:473-477.
[97]Jones S, et al. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science.2010; 330:228-231.
[98]Verhaak RG, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell.2010; 17:98-110.
[99]Harbour JW, et al. Frequent Mutation of BAP1 in Metastasizing Uveal Melanomas. Science.2010
[100]Sheng Z, et al. A genome-wide RNA interference screen reveals an essential CREB3L2-ATF5-MCL1 survival pathway in malignant glioma with therapeutic implications. Nat Med.2010;16:671-677.
[101]Scholl C, et al. Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells. Cell.2009; 137:821-834.
[102]Luo J, et al. Principles of cancer therapy:oncogene and non-oncogene addiction. Cell.2009;136:823-837.
[103]Pomerantz MM, et al. The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer. Nat Genet.2009; 41:882-884.
[104]Vu TH, et al. Loss of IGF2 imprinting is associated with abrogation of long-range intrachromosomal interactions in human cancer cells. Hum Mol Genet.2010; 19:901-919.
[105]Lieberman-Aiden E, et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science.2009; 326:289-293.
[106]Full wood MJ, et al. An oestrogen-receptor-alpha-bound human chromatin interactome. Nature.2009; 462:58-64.
[107]Balwierz PJ, et al. Methods for analyzing deep sequencing expression data: constructing the human and mouse promoterome with deepCAGE data. Genome Biol.2009; 10:R79.
[108]Mattick JS, et al. A global view of genomic information--moving beyond the gene and the master regulator. Trends Genet.2010; 26:21-28.
[109]Petranovic D, Tyo K, Vemuri GN, Nielsen J. Prospects of yeast systems biology for human health:integrating lipid, protein and energy metabolism. FEMS Yeast Res 2010; 10:1046-59.
[110]HawkinsRD, HonGC,RenB.Next-generation genomics:an integrative approach. NatRevGenet2010; 11:476-86.
[111]Lewis TG Network Science:Theory and Practice. Hoboken, NJ:JohnWiley &Sons,2009.
[112]AuffrayC,Chen Z,Hood L.Systems medicine:the future of medical genomics and healthcare.GenomeMed2009; 1:2.
[113]PopelAS,Hunter PJ.Systems biology and physiome projects. WileyInterdiscip-RevSystBiolMed2009; 1:153-8.
[114]Mo ML, Palsson BO. Understanding human metabolic physiology:a genome-to-systems approach. Trends Biotechnol 2009; 27:37-44.
[115]Sreekumar A, Poisson LM, Rajendiran TM et al. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression.Nature2009;457: 910-4.
[116]Deisboeck TS. Personalizing medicine:a systems biology perspective. MolSystBiol2009; 5:249.
[117]Cobelli C, Man CD, Sparacino G, Magni L, De Nicolao G, Kovatchev BP. Diabetes:models, signals, and control. IEEE Rev BiomedEng2009; 2:54-96.
[118]Pabinger S,RaderR,AgrenR, NielsenJ,TrajanoskiZ.MEMOSys:bioinformatics platform for genome-scale metabolic models. BMCSystBiol2011; 5:20.
[119]Palsson B. Metabolic systems biology. FEBS Lett 2009; 583:3900-4.
[120]Bordel S, Agren R,Nielsen J. Sampling the solution space in genome-scale metabolic networks reveals transcriptional regulation in key enzymes. PLoSComput Biol2010; 6:e1000859.
[121]NookaewI,GabrielssonBG,Holmang A, SandbergAS,Nielsen J. Identifying molecular effects of diet through systems biology:influence of herring diet on sterol metabolism and protein turnover inmice. PLoSONE2010; 5:e12361.
[122]Delmore JE, Issa GC, Lemieux ME, et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell.2011; 146(6):904-917.
[123]Kaiser J. Epigenetic drugs take on cancer. Science (New York, NY.2010; 330(6004):576-578.
[124]Lieberman-Aiden E, van Berkum NL, Williams L, et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science (New York, NY.2009;326(5950):289-293.
[125]Flatz L, Roychoudhuri R, Honda M, et al. Single-cell gene-expression profiling reveals qualitatively distinct CD8 T cells elicited by different gene-based vaccines. Proceedings of the National Academy of Sciences of the United States of America.2011; 108(14):5724-5729.
[126]Zimmermann B, Gesell T, Chen D, et al. Monitoring genomic sequences during SELEX using high-throughput sequencing:neutral SELEX. PloS one.2010; 5(2):e9169.
[127]Vijay-Kumar M, Aitken JD, Carvalho FA, et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science (New York, NY.2010; 328(5975):228-231.
[128]Kinross JM, Darzi AW, Nicholson JK. Gut microbiome-host interactions in health and disease. Genome medicine.2011; 3(3):14.
[129]Haas BJ, Gevers D, Earl AM, et al. Chimeric 16S rRNA sequence formation and detection in Sanger and 454-pyrosequenced PCR amplicons. Genome research.2011; 21(3):494-504. [PubMed:21212162]
[130]Quince C, Lanzen A, Davenport RJ, Turnbaugh PJ. Removing noise from pyrosequenced amplicons. BMC bioinformatics.2011; 12:38. [PubMed: 21276213]
[131]Zhang Q, Doak TG, Ye Y. Artificial functional difference between microbial communities caused by length difference of sequencing reads. Pacific Symposium on Biocomputing.2012:259-270.[PubMed:22174281]
[132]Comas I, Borrell S, Roetzer A, et al. Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes. Nature genetics.2011
[133]Toprak E, Veres A, Michel J, et al. Evolutionary paths to antibiotic resistance under dynamically sustained drug selection. Nature genetics.2011
[134]Khosla C, Kapur S, Cane DE (2009) Revisiting the modularity of modular polyketide synthases. Curr Opin Chem Biol 13:135-143
[135]Dietrich JA, Yoshikuni Y, Fisher KJ, Woolard FX, Ockey D, McPhee DJ, Renninger NS, Chang MC, Baker D, Keasling JD (2009) A novel semi-biosynthetic route for artemisinin production using engineered substrate-promiscuous P450(BM3). ACS Chem Biol 4:261-267
[136]Neumann H, Wang K, Davis L, Garcia-Alai M, Chin JW (2010) Encoding multiple unnatural amino acids via evolution of a quadruplet-decoding ribosome. Nature 464:441-444
[137]Wang HH, Isaacs FJ, Carr PA, Sun ZZ, Xu G, Forest CR, Church GM (2009) Programming cells by multiplex genome engineering and accelerated evolution. Nature 460:894-898
[138]Gibson DG, Young L, Chuang RY, Venter JC, Hutchison CA 3rd,Smith HO (2009) Enzymatic assembly of DNA molecules up to several hundred kilobases, Nat Methods 6:343-345
[139]Lu TK, Khalil AS, Collins JJ (2009) Next-generation synthetic gene networks. Nat Biotechnol 27:1139-1150
[140]Nguyen VH, Kim HS, Ha JM, Hong Y, Choy HE, Min JJ (2010) Genetically engineered Salmonella typhimurium as an imageable therapeutic probe for cancer. Cancer Res 70(1):18-23
[141]Widmaier DM, Tullman-Ercek D, Mirsky EA, Hill R, Govindarajan S, Minshull J, Voigt CA (2009) Engineering the Salmonella type III secretion system to export spider silk monomers. Mol Syst Biol 5:309
[142]Neumann H, Wang K, Davis L, Garcia-Alai M, Chin JW (2010) Encoding multiple unnatural amino acids via evolution of a quadruplet-decoding ribosome. Nature 464:441-444
[143]Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325:834-840
[144]Neumann H, Hancock SM, Buning R, Routh A, Chapman L, Somers J, Owen-Hughes T, van Noort J, Rhodes D, Chin JW (2009) A method for genetically installing site-specific acetylation in recombinant histones defines the effects of H3 K56 acetylation. Mol Cell 36:153-163
[145]Zheng N, Zhang X, Rosania GR. Effect of phospholipidosis on the cellular pharmacokinetics of chloroquine. J Pharmacol Exp Ther.2011; 336:661-671.
[146]Baik, J.; Rosania, GR. Capsular Xenobiotic Inclusions within Autophagosome-like Bodies; American Association of Pharmaceutical Scientists Annual Meeting; New Orleans, LA, USA:2010.
[147]Chatman LA, Morton D, Johnson TO, Anway SD. A strategy for risk management of druginduced phospholipidosis. Toxicol Pathol.2009; 37:997-1005.
[148]de Souza W, Rodrigues JC. Sterol Biosynthesis Pathway as Target for Anti-trypanosomatid Drugs. Interdiscip Perspect Infect Dis.2009; 2009:642502.
[149]Aubel D, Fussenegger M:Mammalian synthetic biology-from tools to therapies. Bioessays 2010; 32:332-345.
[150]Weber W, Fussenegger M.2009. Engineering of synthetic mammalian gene networks. Chem Biol 16:287-97.
[151]Tigges M, De'nervaud N, Greber D, et al.2010. A synthetic low-frequency mammalian oscillator. Nucleic Acids Res In press.
[152]Tigges M, Marquez-Lago TT, Stelling J, et al.2009. A tunable synthetic mammalian oscillator. Nature 457:309-12.
[153]T. Danino, O. Mondragon-Palomino, L. Tsimring, J. Hasty, Nature 463,326 (2010).
[154]D. J. Dwyer, M. A. Kohanski, J. J. Collins, Curr. Opin. Microbiol.12,482 (2009).
[155]Wise de Valdez MR, Nimmo D, Betz J, Gong HF, James AA, Alphey L, Black WC 4th:Genetic elimination of dengue vector mosquitoes. Proc Natl Acad Sci USA 2011; 108:4772-4775.
[156]Planson AG, Carbonell P, Grigoras I, Faulon JL:Engineering antibiotic production and overcoming bacterial resistance. Biotechnol J 2011; 6:812-825.
[157]Lee DS, Burd H, Liu J et al. Comparative genome-scale metabolic reconstruction and flux balance analysis of multiple Staphylococcus aureus genomes identify novel antimicrobial drug targets. J Bacteriol 2009; 191: 4015-24.
[158]Pethe K, Sequeira PC, Agarwalla S et al. A chemical genetic screen in Mycobacterium tuberculosis identifies carbon-source-dependent growth inhibitors devoid of in vivo efficacy. Nat Commun 2010; 1:57.
[159]Gross H. Genomic mining—a concept for the discovery of new bioactive natural products. Curr Opin Drug Discov Devel 2009; 12:207-19.
[160]Li M, Ung P, Zajkowski J et al. Automated genome mining for natural products. BMC Bioinformatics 2009; 10:185.
[161]Choi SK, Park SY, Kim R et al. Identification of a polymyxin synthetase gene cluster of Paenibacillus polymyxa and heterologous expression of the gene in Bacillus subtilis. J Bacteriol 2009; 191:3350-8.
[162]Medema MH, Breitling R, Bovenberg R et al. Exploiting plug-and-play synthetic biology for drug discovery and production in microorganisms. Nat Rev Microbiol 2011; 9:131-7.
[163]Miller, S. J., and Clardy, J. (2009) Natural products:Beyond grind and find. Nat. Chem.1,261-263.
[164]Fischbach, M. A., and Walsh, C. T. (2009) Antibiotics for emerging pathogens. Science 325,1089-1093.
[2]Duprez, E., Wagner, K., Koch, H., and Tenen, D. G (2003) C/EBPbeta:a major PML-RARA-responsive gene in retinoic acid-induced differentiation of APL cells. Embo J 22,5806-5816.
[3]Hirai, H., Zhang, P., Dayaram, T., Hetherington, C. J., Mizuno, S., Imanishi, J., Akashi, K., and Tenen, D. G (2006) C/EBPbeta is required for 'emergency' granulopoiesis. Nat Immunol 7,732-739.
[4]Weinmann, A. S. (2004) Novel ChlP-based strategies to uncover transcription factor target genes in the immune system. Nat Rev Immunol 4,381-386.
[5]Greenbaum, S., and Zhuang, Y (2002) Identification of E2A target genes in B lymphocyte development by using a gene tagging-based chromatin immunoprecipitation system. Proc Natl Acad Sci U S A 99,15030-15035.
[6]Weinmann, A. S., Bartley, S. M., Zhang, T., Zhang, M. Q., and Farnham, P. J. (2001) Use of chromatin immunoprecipitation to clone novel E2F target promoters. Mol Cell Biol 21,6820-6832.
[7]Weinmann, A. S., and Farnham, P. J. (2002) Identification of unknown target genes of human transcription factors using chromatin immunoprecipitation. Methods 26,37-47.
[8]Hug, B. A., Ahmed, N., Robbins, J. A., and Lazar, M. A. (2004) A chromatin immunoprecipitation screen reveals protein kinase Cbeta as a direct RUNX1 target gene. J Biol Chem 279,825-830.
[9]Hao, B., Miao, X., Li, Y, Zhang, X., Sun, T., Liang, G, Zhao, Y, Zhou, Y, Wang, H., Chen, X., Zhang, L., Tan, W., Wei, Q., Lin, D., and He, F. (2006) A novel T-77C polymorphism in DNA repair gene XRCC1 contributes to diminished promoter activity and increased risk of non-small cell lung cancer. Oncogene 25,3613-3620.
[10]Matsumoto, M., Tanaka, T., Kaisho, T., Sanjo, H., Copeland, N. G, Gilbert, D. J., Jenkins, N. A., and Akira, S. (1999) A novel LPS-inducible C-type lectin is a transcriptional target of NF-IL6 in macrophages. J Immunol 163,5039-5048.
[11]Osada, S., Yamamoto, H., Nishihara, T., and Imagawa, M. (1996) DNA binding specificity of the CCAAT/enhancer-binding protein transcription factor family. J Biol Chem 271,3891-3896.
[12]Hochepied, T., Berger, F. G, Baumann, H., and Libert, C. (2003) Alpha(1)-acid glycoprotein:an acute phase protein with inflammatory and immunomodulating properties. Cytokine Growth Factor Rev 14,25-34.
[13]Theilgaard-Monch, K., Jacobsen, L. C., Rasmussen, T., Niemann, C. U., Udby, L., Borup, R., Gharib, M., Arkwright, P. D., Gombart, A. F., Calafat, J., Porse, B. T., and Borregaard, N. (2005) Highly glycosylated alphal-acid glycoprotein is synthesized in myelocytes, stored in secondary granules, and released by activated neutrophils. J Leukoc Biol 78,462-470.
[14]Berridge, M. J., Bootman, M. D., and Roderick, H. L. (2003) Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 4,517-529.
[15]Sugiyama, T., Yamamoto-Hino, M., Miyawaki, A., Furuichi, T., Mikoshiba, K., and Hasegawa, M. (1994) Subtypes of inositol 1,4,5-trisphosphate receptor in human hematopoietic cell lines:dynamic aspects of their cell-type specific expression. FEBS Lett 349,191-196.
[16]Timson, D. J., and Reece, R. J. (2003) Identification and characterisation of human aldose 1-epimerase. FEBS Lett 543,21-24.
[17]Horak, C. E., Mahajan, M. C., Luscombe, N. M., Gerstein, M., Weissman, S. M., and Snyder, M. (2002) GATA-1 binding sites mapped in the beta-globin locus by using mammalian chIp-chip analysis. Proc Natl Acad Sci U S A 99,2924-2929.
[18]Weinmann, A. S., Yan, P. S., Oberley, M. J., Huang, T. H., and Farnham, P. J. (2002) Isolating human transcription factor targets by coupling chromatin immunoprecipitation and CpG island microarray analysis. Genes Dev 16,235-244.
[19]Cawley, S., Bekiranov, S., Ng, H. H., Kapranov, P., Sekinger, E. A., Kampa, D., Piccolboni, A., Sementchenko, V., Cheng, J., Williams, A. J., Wheeler, R., Wong, B., Drenkow, J., Yamanaka, M., Patel, S., Brubaker, S., Tammana, H., Helt, G, Struhl, K., and Gingeras, T. R. (2004) Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell 116,499-509.
[20]Kim, T. H., Barrera, L. O., Zheng, M., Qu, C., Singer, M. A., Richmond, T. A., Wu, Y, Green, R. D., and Ren, B. (2005) A high-resolution map of active promoters in the human genome. Nature 436,876-880.
[21]Nelson, E. A., Walker, S. R., Alvarez, J. V., and Frank, D. A. (2004) Isolation of unique STAT5 targets by chromatin immunoprecipitation-based gene identification. J Biol Chem 279,54724-54730.
[22]Barski, A., and Frenkel, B. (2004) ChIP Display:novel method for identification of genomic targets of transcription factors. Nucleic Acids Res 32, e104.
[23]Hearnes, J. M., Mays, D. J., Schavolt, K. L., Tang, L., Jiang, X., and Pietenpol, J. A. (2005) Chromatin immunoprecipitation-based screen to identify functional genomic binding sites for sequence-specific transactivators. Mol Cell Biol 25,10148-10158.
[24]Schrem, H., Klempnauer, J., and Borlak, J. (2004) Liver-enriched transcription factors in liver function and development. Part Ⅱ:the C/EBPs and D site-binding protein in cell cycle control, carcinogenesis, circadian gene regulation, liver regeneration, apoptosis, and liver-specific gene regulation. Pharmacol Rev 56,291-330.
[25]Ramji, D. P., and Foka, P. (2002) CCAAT/enhancer-binding proteins:structure, function and regulation. Biochem J 365,561-575.
[26]Friedman, J. R., Larris, B., Le, P. P., Peiris, T. H., Arsenlis, A., Schug, J., Tobias, J. W., Kaestner, K. H., and Greenbaum, L. E. (2004) Orthogonal analysis of C/EBPbeta targets in vivo during liver proliferation. Proc Natl Acad Sci U S A 101,12986-12991.
[27]Yonggang Ke, Luvena L. Ong, William M. Shih, Peng Yin (2012) Three-Dimensional structures self-assembled from DNA bricks. Science 30 November 2012:Vol.338 no.6111 pp.1177-1183 DOI:10.1126/science. 1227268
[28]Editing the Genome:Scientists Unveil New Tools for Rewriting the Code of Life. Science News. July 15,2011
[29]George M. Church, Yuan Gao, Sriram Kosuri. Next-Generation Digital Information Storage in DNA. Published Online August 16 2012. Science 28 September 2012:Vol.337 no.6102 p.1628 DOI:10.1126/science.1226355
[30]Arkin, A. P. & Schaffer, D. V. Network news:innovations in 21st century systems biology. Cell 144,844-849 (2011).
[31]Roy, S. et al. Identification of functional elements and regulatory circuits by Drosophila modENCODE. Science 330,1787-1797 (2010).
[32]Smolke, C. D. & Silver, P. A. Informing biological design by integration of systems and synthetic biology. Cell 144,855-859 (2011).
[33]Jasny, B. R. & Zahn, L. M. Genome-sequencing anniversary. A celebration of the genome, part I. Science 331,546 (2011).
[34]Nielsen, R., Paul, J. S., Albrechtsen, A. & Song, Y. S. Genotype and SNP calling from next-generation sequencing data. Nature Rev. Genet.12,443-451 (2011).
[35]Kosuri, S. et al. Scalable gene synthesis by selective amplification of DNA pools from high-fidelity microchips. Nature Biotech.28,1295-1299 (2010).
[36]Matzas, M. et al. High-fidelity gene synthesis by retrieval of sequence-verified DNA identified using high-throughput pyrosequencing. Nature Biotech.28, 1291-1294 (2010).
[37]Quan, J. et al. Parallel on-chip gene synthesis and application to optimization of protein expression. Nature Biotech.29,449-452 (2011).
[38]Gibson, D. G. et al. Creation of a bacterial cell controlled by a chemically synthesized genome. Science 329,52-56 (2010).
[39]Bedau, M. et al. Life after the synthetic cell. Nature 465,422-424 (2010).
[40]Burrill, D. R. & Silver, P. A. Making cellular memories. Cell 140,13-18 (2010).
[41]Danino, T., Mondragon-Palomino, O., Tsimring, L. & Hasty, J. A synchronized quorum of genetic clocks. Nature 463,326-330 (2010).
[42]Leisner, M., Bleris, L., Lohmueller, J., Xie, Z. & Benenson, Y. Rationally designed logic integration of regulatory signals in mammalian cells. Nature Nanotechnol.5,666-670 (2010).
[43]Toettcher, J. E., Mock, C., Batchelor, E., Loewer, A. & Lahav, G. A synthetic-natural hybrid oscillator in human cells. Proc. Natl Acad. Sci. USA 107,17047-17052(2010).
[44]Xie, Z., Wroblewska, L., Prochazka, L., Weiss, R. & Benenson, Y. Multi-input RNAi-based logic circuit for identification of specific cancer cells. Science 333, 1307-1311(2011).
[45]Nandagopal, N. & Elowitz, M. B. Synthetic biology:integrated gene circuits. Science 333,1244-1248 (2011).
[46]Aubel, D. & Fussenegger, M. Mammalian synthetic biology—from tools to therapies. Bioessays 32,332-345 (2010).
[47]Weber, W. & Fussenegger, M. Synthetic gene networks in mammalian cells. Curr. Opin. Biotechnol.692,235-249 (2010).
[48]Weber, W. & Fussenegger, M. Molecular diversity—the toolbox for synthetic gene switches and networks. Curr. Opin. Chem. Biol.15,414-420 (2011).
[49]Wieland, M. & Fussenegger, M. Ligand-dependent regulatory RNA parts for synthetic biology in eukaryotes. Curr. Opin. Biotechnol.21,760-765 (2010).
[50]Yao, G., Tan, C., West, M., Nevins, J. R. & You, L. Origin of bistability underlying mammalian cell cycle entry. Mol. Syst. Biol.7,485 (2011).
[51]Karlsson, M., Weber, W. & Fussenegger, M. De novo design and construction of an inducible gene expression system in mammalian cells. Methods Enzymol. 497,239-253(2011).
[52]Aubel, D. & Fussenegger, M. Watch the clock-engineering biological systems to be on time. Curr. Opin. Genet. Dev.20,634-643 (2010).
[53]Tigges, M., Denervaud, N., Greber, D., Stelling, J. & Fussenegger, M. A synthetic low-frequency mammalian oscillator. Nucleic Acids Res.38, 2702-2711 (2010).
[54]Khalil, A. S. & Collins, J. J. Synthetic biology:applications come of age. Nature Rev. Genet.11,367-379 (2010).
[55]Kemmer, C. et al. A designer network coordinating bovine artificial insemination by ovulation-triggered release of implanted sperms. J. Control. Release 150,23-29(2011).
[56]Kemmer, C. et al. Self-sufficient control of urate homeostasis in mice by a synthetic circuit. Nature Biotech.28,355-360 (2010).
[57]Ye, H., Daoud-El Baba, M., Peng, R. W. & Fussenegger, M. A synthetic optogenetic transcription device enhances blood-glucose homeostasis in mice. Science 332,1565-1568 (2011).
[58]The first optogenetic device that controls the production of a therapeutic protein in an animal disease model is described in this paper.
[59]Fears, R. & ter Meulen, V. The potential of synthetic biology:a view from the European Academies Science Advisory Council. Nature Rev. Microbiol.9,222 (2011).
[60]Ruder, W. C., Lu, T. & Collins, J. J. Synthetic biology moving into the clinic. Science 333,1248-1252 (2011).
[61]Burbelo, P. D., Ching, K. H., Bush, E. R., Han, B. L. & Iadarola, M. J. Antibody-profiling technologies for studying humoral responses to infectious agents. Expert Rev. Vaccines 9,567-578 (2010).
[62]Chandra, A., Wormser, G P., Marques, A. R., Latov, N. & Alaedini, A. Anti-Borrelia burgdorferi antibody profile in post-Lyme disease syndrome. Clin. Vaccine Immunol.18,767-771 (2011).
[63]Burbelo, P. D. et al. LIPS arrays for simultaneous detection of antibodies against partial and whole proteomes of HCV, HIV and EBV. Mol. Biosyst.7, 1453-1462(2011).
[64]Yang, J. & Reth, M. Oligomeric organization of the B-cell antigen receptor on resting cells. Nature 467,465-469 (2010).
[65]McMichael AJ, Borrow P, Tomaras GD, Goonetilleke N, Haynes BF. The immune response during acute HIV-1 infection:clues for vaccine development. Nat Rev Immunol 2010; 10:11-23.
[66]Kaufmann SH. Future vaccination strategies against tuberculosis:thinking outside the box. Immunity 2010; 33:567-77.
[67]Bambini S, Rappuoli R. The use of genomics in microbial vaccine development. Drug Discov Today 2009; 14:252-60.
[68]Raab D, Graf M, Notka F, Schodl T, Wagner R. The Gene Optimizer Algorithm: using a sliding window approach to cope with the vast sequence space in multiparameter DNA sequence optimization. Syst Synth Biol 2010; 4:215-25.
[69]Maertens B, Spriestersbach A, von Groll U, Roth U, Kubicek J, Gerrits M, et al. Gene optimization mechanisms:a multi-gene study reveals a high success rate of full-length human proteins expressed in Escherichia coli. Protein Sci 2010; 19:1312-26.
[70]Kindsmuller K, Wagner R. Synthetic biology:impact on the design of innovative vaccines. Hum Vaccin.2011 Jun;7(6):658-62. Epub 2011 Jun 1.
[71]Bazhan SI, Karpenko LI, Ilyicheva TN, Belavin PA, Seregin SV, Danilyuk NK, et al. Rational design based synthetic polyepitope DNA vaccine for eliciting HIV-specific CD8+T cell responses. Mol Immunol 2010; 47:1507-15.
[72]Barouch DH, O'Brien KL, Simmons NL, King SL, Abbink P, Maxfield LF, et al. Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys. Nat Med 2010; 16:319-23
[73]Chiarella P, Massi E, De Robertis M, Fazio VM,Signori E. Recent advances in epitope design for immunotherapy of cancer. Recent Pat Anticancer Drug Discov 2009; 4:227-40.
[74]Alexander J, Bilsel P, del Guercio MF, Marinkovic- Petrovic A, Southwood S, Stewart S, et al. Identification of broad binding class I HLA supertype epitopes to provide universal coverage of influenza A virus. Hum Immunol 2010; 71:468-74.
[75]Larsen MV, Lelic A, Parsons R, Nielsen M, Hoof I, Lamberth K, et al. Identification of CD8+T cell epitopes in the West Nile virus polyprotein by everse-immunology using NetCTL. PLoSOne 2010; 5:12697.
[76]Salimi N, Fleri W, Peters B, Sette A. Design and utilization of epitope-based databases and predictive tools. Immunogenetics 2010; 62:185-96.
[77]Tian S, Liu Z, Donahue C, Noh HS, Falo LD Jr, You Z. Transcriptional IL-15-directed in vivo DC targeting DNA vaccine. Gene Ther 2009; 16:1260-70
[78]Bringmann A, Held SA, Heine A, Brossart P, RNA vaccine in cancer treatment. J Biomed Biotechnol 2010,623687
[79]Mueller S, Coleman JR, Papamichail D, Ward CB, Nimnual A, Futcher B, et al. Live attenuated influenza virus vaccines by computer-aided rational design.Nat Biotechnol 2010; 28:723-6.
[80]Gibson DG, Glass JI, Lartigue C, Noskov VN, Chuang RY, Algire MA, et al. Creation of a bacterial cell controlled by a chemically synthesized genome.Science 2010; 329:52-6.
[81]Burbelo PD, Ching KH, Han BL, Klimavicz CM, Iadarola MJ. Synthetic biology for translational research. Am J Transl Res 2010; 2:381-9
[82]Wise de Valdez, M. R. et al. Genetic elimination of dengue vector mosquitoes. Proc. Natl Acad. Sci. USA 108,4772-4775 (2011).
[83]Windbichler, N. et al. A synthetic homing endonuclease-based gene drive system in the human malaria mosquito. Nature 473,212-215 (2011).
[84]Subbaraman, N. Science snipes at Oxitec transgenic-mosquito trial. Nature Biotech.29,9-11 (2011).
[85]Allison, K. R., Brynildsen, M. P. & Collins, J. J. Metabolite-enabled eradication of bacterial persisters by aminoglycosides. Nature 473,216-220 (2011).
[86]Lee, H. H., Molla, M. N., Cantor, C. R. & Collins, J. J. Bacterial charity work leads to population-wide resistance. Nature 467,82-85 (2010).
[87]Kohanski, M. A., DePristo, M. A. & Collins, J. J. Sublethal antibiotic treatment leads to multidrug resistance via radical-induced mutagenesis. Mol. Cell 37, 311-320(2010).
[88]Kohanski, M. A., Dwyer, D. J. & Collins, J. J. How antibiotics kill bacteria: from targets to networks. Nature Rev. Microbiol.8,423-435 (2010).
[89]Forbes, N. S. Engineering the perfect (bacterial) cancer therapy. Nature Rev. Cancer 10,785-794 (2010).
[90]Voelkel, C. et al. Protein transduction from retroviral Gag precursors. Proc. Natl Acad. Sci. USA 107,7805-7810 (2010).
[91]Zhang, F. et al. Efficient construction of sequence-specific TAL effectors for modulating mammalian transcription. Nature Biotech.29,149-153 (2011).
[92]Metzker ML. Sequencing technologies-the next generation. Nat Rev Genet. 2010; 11:31-46.
[93]Mardis ER, et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med.2009; 361:1058-1066.
[94]Pleasance ED, et al. A comprehensive catalogue of somatic mutations from a human cancer genome. Nature.2010; 463:191-196.
[95]Taylor BS, et al. Integrative genomic profiling of human prostate cancer. Cancer Cell.2010;18:11-22.
[96]Lee W, et al. The mutation spectrum revealed by paired genome sequences from a lung cancer patient. Nature.2010; 465:473-477.
[97]Jones S, et al. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science.2010; 330:228-231.
[98]Verhaak RG, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell.2010; 17:98-110.
[99]Harbour JW, et al. Frequent Mutation of BAP1 in Metastasizing Uveal Melanomas. Science.2010
[100]Sheng Z, et al. A genome-wide RNA interference screen reveals an essential CREB3L2-ATF5-MCL1 survival pathway in malignant glioma with therapeutic implications. Nat Med.2010;16:671-677.
[101]Scholl C, et al. Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells. Cell.2009; 137:821-834.
[102]Luo J, et al. Principles of cancer therapy:oncogene and non-oncogene addiction. Cell.2009;136:823-837.
[103]Pomerantz MM, et al. The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer. Nat Genet.2009; 41:882-884.
[104]Vu TH, et al. Loss of IGF2 imprinting is associated with abrogation of long-range intrachromosomal interactions in human cancer cells. Hum Mol Genet.2010; 19:901-919.
[105]Lieberman-Aiden E, et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science.2009; 326:289-293.
[106]Full wood MJ, et al. An oestrogen-receptor-alpha-bound human chromatin interactome. Nature.2009; 462:58-64.
[107]Balwierz PJ, et al. Methods for analyzing deep sequencing expression data: constructing the human and mouse promoterome with deepCAGE data. Genome Biol.2009; 10:R79.
[108]Mattick JS, et al. A global view of genomic information--moving beyond the gene and the master regulator. Trends Genet.2010; 26:21-28.
[109]Petranovic D, Tyo K, Vemuri GN, Nielsen J. Prospects of yeast systems biology for human health:integrating lipid, protein and energy metabolism. FEMS Yeast Res 2010; 10:1046-59.
[110]HawkinsRD, HonGC,RenB.Next-generation genomics:an integrative approach. NatRevGenet2010; 11:476-86.
[111]Lewis TG Network Science:Theory and Practice. Hoboken, NJ:JohnWiley &Sons,2009.
[112]AuffrayC,Chen Z,Hood L.Systems medicine:the future of medical genomics and healthcare.GenomeMed2009; 1:2.
[113]PopelAS,Hunter PJ.Systems biology and physiome projects. WileyInterdiscip-RevSystBiolMed2009; 1:153-8.
[114]Mo ML, Palsson BO. Understanding human metabolic physiology:a genome-to-systems approach. Trends Biotechnol 2009; 27:37-44.
[115]Sreekumar A, Poisson LM, Rajendiran TM et al. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression.Nature2009;457: 910-4.
[116]Deisboeck TS. Personalizing medicine:a systems biology perspective. MolSystBiol2009; 5:249.
[117]Cobelli C, Man CD, Sparacino G, Magni L, De Nicolao G, Kovatchev BP. Diabetes:models, signals, and control. IEEE Rev BiomedEng2009; 2:54-96.
[118]Pabinger S,RaderR,AgrenR, NielsenJ,TrajanoskiZ.MEMOSys:bioinformatics platform for genome-scale metabolic models. BMCSystBiol2011; 5:20.
[119]Palsson B. Metabolic systems biology. FEBS Lett 2009; 583:3900-4.
[120]Bordel S, Agren R,Nielsen J. Sampling the solution space in genome-scale metabolic networks reveals transcriptional regulation in key enzymes. PLoSComput Biol2010; 6:e1000859.
[121]NookaewI,GabrielssonBG,Holmang A, SandbergAS,Nielsen J. Identifying molecular effects of diet through systems biology:influence of herring diet on sterol metabolism and protein turnover inmice. PLoSONE2010; 5:e12361.
[122]Delmore JE, Issa GC, Lemieux ME, et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell.2011; 146(6):904-917.
[123]Kaiser J. Epigenetic drugs take on cancer. Science (New York, NY.2010; 330(6004):576-578.
[124]Lieberman-Aiden E, van Berkum NL, Williams L, et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science (New York, NY.2009;326(5950):289-293.
[125]Flatz L, Roychoudhuri R, Honda M, et al. Single-cell gene-expression profiling reveals qualitatively distinct CD8 T cells elicited by different gene-based vaccines. Proceedings of the National Academy of Sciences of the United States of America.2011; 108(14):5724-5729.
[126]Zimmermann B, Gesell T, Chen D, et al. Monitoring genomic sequences during SELEX using high-throughput sequencing:neutral SELEX. PloS one.2010; 5(2):e9169.
[127]Vijay-Kumar M, Aitken JD, Carvalho FA, et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science (New York, NY.2010; 328(5975):228-231.
[128]Kinross JM, Darzi AW, Nicholson JK. Gut microbiome-host interactions in health and disease. Genome medicine.2011; 3(3):14.
[129]Haas BJ, Gevers D, Earl AM, et al. Chimeric 16S rRNA sequence formation and detection in Sanger and 454-pyrosequenced PCR amplicons. Genome research.2011; 21(3):494-504. [PubMed:21212162]
[130]Quince C, Lanzen A, Davenport RJ, Turnbaugh PJ. Removing noise from pyrosequenced amplicons. BMC bioinformatics.2011; 12:38. [PubMed: 21276213]
[131]Zhang Q, Doak TG, Ye Y. Artificial functional difference between microbial communities caused by length difference of sequencing reads. Pacific Symposium on Biocomputing.2012:259-270.[PubMed:22174281]
[132]Comas I, Borrell S, Roetzer A, et al. Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes. Nature genetics.2011
[133]Toprak E, Veres A, Michel J, et al. Evolutionary paths to antibiotic resistance under dynamically sustained drug selection. Nature genetics.2011
[134]Khosla C, Kapur S, Cane DE (2009) Revisiting the modularity of modular polyketide synthases. Curr Opin Chem Biol 13:135-143
[135]Dietrich JA, Yoshikuni Y, Fisher KJ, Woolard FX, Ockey D, McPhee DJ, Renninger NS, Chang MC, Baker D, Keasling JD (2009) A novel semi-biosynthetic route for artemisinin production using engineered substrate-promiscuous P450(BM3). ACS Chem Biol 4:261-267
[136]Neumann H, Wang K, Davis L, Garcia-Alai M, Chin JW (2010) Encoding multiple unnatural amino acids via evolution of a quadruplet-decoding ribosome. Nature 464:441-444
[137]Wang HH, Isaacs FJ, Carr PA, Sun ZZ, Xu G, Forest CR, Church GM (2009) Programming cells by multiplex genome engineering and accelerated evolution. Nature 460:894-898
[138]Gibson DG, Young L, Chuang RY, Venter JC, Hutchison CA 3rd,Smith HO (2009) Enzymatic assembly of DNA molecules up to several hundred kilobases, Nat Methods 6:343-345
[139]Lu TK, Khalil AS, Collins JJ (2009) Next-generation synthetic gene networks. Nat Biotechnol 27:1139-1150
[140]Nguyen VH, Kim HS, Ha JM, Hong Y, Choy HE, Min JJ (2010) Genetically engineered Salmonella typhimurium as an imageable therapeutic probe for cancer. Cancer Res 70(1):18-23
[141]Widmaier DM, Tullman-Ercek D, Mirsky EA, Hill R, Govindarajan S, Minshull J, Voigt CA (2009) Engineering the Salmonella type III secretion system to export spider silk monomers. Mol Syst Biol 5:309
[142]Neumann H, Wang K, Davis L, Garcia-Alai M, Chin JW (2010) Encoding multiple unnatural amino acids via evolution of a quadruplet-decoding ribosome. Nature 464:441-444
[143]Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325:834-840
[144]Neumann H, Hancock SM, Buning R, Routh A, Chapman L, Somers J, Owen-Hughes T, van Noort J, Rhodes D, Chin JW (2009) A method for genetically installing site-specific acetylation in recombinant histones defines the effects of H3 K56 acetylation. Mol Cell 36:153-163
[145]Zheng N, Zhang X, Rosania GR. Effect of phospholipidosis on the cellular pharmacokinetics of chloroquine. J Pharmacol Exp Ther.2011; 336:661-671.
[146]Baik, J.; Rosania, GR. Capsular Xenobiotic Inclusions within Autophagosome-like Bodies; American Association of Pharmaceutical Scientists Annual Meeting; New Orleans, LA, USA:2010.
[147]Chatman LA, Morton D, Johnson TO, Anway SD. A strategy for risk management of druginduced phospholipidosis. Toxicol Pathol.2009; 37:997-1005.
[148]de Souza W, Rodrigues JC. Sterol Biosynthesis Pathway as Target for Anti-trypanosomatid Drugs. Interdiscip Perspect Infect Dis.2009; 2009:642502.
[149]Aubel D, Fussenegger M:Mammalian synthetic biology-from tools to therapies. Bioessays 2010; 32:332-345.
[150]Weber W, Fussenegger M.2009. Engineering of synthetic mammalian gene networks. Chem Biol 16:287-97.
[151]Tigges M, De'nervaud N, Greber D, et al.2010. A synthetic low-frequency mammalian oscillator. Nucleic Acids Res In press.
[152]Tigges M, Marquez-Lago TT, Stelling J, et al.2009. A tunable synthetic mammalian oscillator. Nature 457:309-12.
[153]T. Danino, O. Mondragon-Palomino, L. Tsimring, J. Hasty, Nature 463,326 (2010).
[154]D. J. Dwyer, M. A. Kohanski, J. J. Collins, Curr. Opin. Microbiol.12,482 (2009).
[155]Wise de Valdez MR, Nimmo D, Betz J, Gong HF, James AA, Alphey L, Black WC 4th:Genetic elimination of dengue vector mosquitoes. Proc Natl Acad Sci USA 2011; 108:4772-4775.
[156]Planson AG, Carbonell P, Grigoras I, Faulon JL:Engineering antibiotic production and overcoming bacterial resistance. Biotechnol J 2011; 6:812-825.
[157]Lee DS, Burd H, Liu J et al. Comparative genome-scale metabolic reconstruction and flux balance analysis of multiple Staphylococcus aureus genomes identify novel antimicrobial drug targets. J Bacteriol 2009; 191: 4015-24.
[158]Pethe K, Sequeira PC, Agarwalla S et al. A chemical genetic screen in Mycobacterium tuberculosis identifies carbon-source-dependent growth inhibitors devoid of in vivo efficacy. Nat Commun 2010; 1:57.
[159]Gross H. Genomic mining—a concept for the discovery of new bioactive natural products. Curr Opin Drug Discov Devel 2009; 12:207-19.
[160]Li M, Ung P, Zajkowski J et al. Automated genome mining for natural products. BMC Bioinformatics 2009; 10:185.
[161]Choi SK, Park SY, Kim R et al. Identification of a polymyxin synthetase gene cluster of Paenibacillus polymyxa and heterologous expression of the gene in Bacillus subtilis. J Bacteriol 2009; 191:3350-8.
[162]Medema MH, Breitling R, Bovenberg R et al. Exploiting plug-and-play synthetic biology for drug discovery and production in microorganisms. Nat Rev Microbiol 2011; 9:131-7.
[163]Miller, S. J., and Clardy, J. (2009) Natural products:Beyond grind and find. Nat. Chem.1,261-263.
[164]Fischbach, M. A., and Walsh, C. T. (2009) Antibiotics for emerging pathogens. Science 325,1089-1093.