系統識別號 U0026-2207201316261300
論文名稱(中文) 系統生物學方法應用於高通量全基因組資料之解析
論文名稱(英文) Systems Biology Approaches for Analysis of High-Throughput Genome-Wide Data
校院名稱 成功大學
系所名稱(中) 資訊工程學系碩博士班
系所名稱(英) Institute of Computer Science and Information Engineering
學年度 101
學期 2
出版年 102
研究生(中文) 陳偉銘
研究生(英文) Wei-Ming Chen
學號 P78981265
學位類別 博士
語文別 英文
論文頁數 107頁
口試委員 指導教授-蔣榮先
中文關鍵字 系統生物學  激酶組調控網路  磷酸化  分類  演算法  ADTree決策樹  次世代定序  核小體定位 
英文關鍵字 Systems Biology  Kinome Regulatory Network  Phosphorylation  Classification  Algorithm  ADTree  Next-Generation Sequencing  Nucleosome Positioning 
中文摘要 解決生物的複雜性與高資料維度詛咒是深入探討生物作用機制首要挑戰的任務。系統生物學概念提供一個良好的基礎架構來剖析生物複雜性並建立生物與電腦技術之間的合作橋樑。挑戰的任務可細分為兩方面來探討:如何處理超大量資料的問題與如何逐步地解開生物的作用方式。本論文中提供了一個系統生物學架構,該架構是一個循環的機制:能使生物問題驅動電腦技術提升;進而驅動生醫網路建構的完整性;最後再反饋回生物本體以便回答生物問題。首先,該架構包含了一套系統性網路模組來處理超大資料,並且應用於建構激酶組調控網路與解開磷酸化調控之複雜性。第二,該架構包括一套系統性分析方法能有效逐步地檢驗與分析由生物網路所產生的新假設,並且應用於解析核孔複合物的機制,其主要藉由發展數學模型方法來分析巨大資料並反饋回生物本質問題。總結上述,本論文主要致力於發展系統生物學方法,其貢獻包含了:建立新的數學模型方法以解決複雜生物問題;分析巨量數據並且通過統計方法來驗證生物假設;資訊視覺化以助於透視生物複雜性;最後,利用循環的機制來解決生物問題並且突破電腦技術瓶頸。
英文摘要 The two main challenges from the biological complexity and high data dimensionality are to understand how biological systems function and to determine how enormous data can be dealt with, respectively. The objective of this dissertation is to propose a systems biology framework and aims to target the problem with the purpose of exploring the biological complexity and high data dimensionality. This framework that contains two systems biology approaches is a constantly evolving loop with three elements: biology, computation, and network. In our research, we first have proposed a systems network that can analyze big data, build a kinome network from huge datasets, and uncover the complex regulation by phosphorylation. Secondly, we have developed a systems analysis that can decipher nuclear pore complexes (NPCs) mechanism by analyzing tremendous data and providing feedback to biology. In conclusion, our research contributes to the development of systems biology framework in four ways: 1) it creates new models in order to address new biological questions, 2) it summarizes and describes the data through statistical tests to validate the hypothesis, 3) it gives visualization of the analyzed results effectively to break down the biological complexity, and 4) it provides an evolving cycle framework to address biological issues and to advance in computation.
論文目次 中文摘要 I
3.2.1 Datasets used to predict Phosphorylation networks 21
3.2.2 Data Processing 21
3.2.3 Model Learning 25
3.3 RESULTS 27
3.2.1 PhosphoChain evaluation 28
3.2.2 Reconstruction of MAPK Pathways 34
3.2.3 Predicting Phosphorylation Sites 40
3.2.4 Reconstruction of the Genome-wide Kinome Network 47
3.4 SUMMARY 54
4.2.1 Telomeric enrichment model 60
4.2.2 Nucleosome fluctuation model 62
4.2.3 Subtelomeric association model 65
4.2.4 Visualization 67
4.3 RESULTS 68
4.3.3 Detection of the enrichment pattern of subtelomeric genes silencing 68
4.3.4 Identification of subtelomeric chromatin changes in nucleosome positioning and occupancy 71
4.3.5 Measurement of the physical interactions of NPC protein with RP genes and subtelomeric DNA 76
4.4 SUMMARY 83
5.1 REMARKS 84
5.2.1 Extending PhosphoChain and improvement of kinome network building 86
5.2.2 Extending NPCparser and providing feedback to biology 88
5.2.3 Multi-scale visualizations in multiple levels for big data 89
5.2.4 New statistical and mathematical methods for big data 90
參考文獻 Abdulrehman D, Monteiro PT, Teixeira MC, Mira NP, Lourenco AB, dos Santos SC, Cabrito TR, Francisco AP, Madeira SC, Aires RS, Oliveira AL, Sa-Correia I, Freitas AT, "YEASTRACT: providing a programmatic access to curated transcriptional regulatory associations in Saccharomyces cerevisiae through a web services interface," Nucleic Acids Res, 39: D136-140, 2011.

Aitchison JD, Rout MP, "The yeast nuclear pore complex and transport through it," Genetics, 190: 855-883, 2012.

Alber F, Dokudovskaya S, Veenhoff LM, Zhang W, Kipper J, Devos D, Suprapto A, Karni-Schmidt O, Williams R, Chait BT, Sali A, Rout MP, "The molecular architecture of the nuclear pore complex," Nature, 450: 695-701, 2007.

Albert R, "Network inference, analysis, and modeling in systems biology," Plant Cell, 19: 3327-3338, 2007.

Amlacher S, Sarges P, Flemming D, van Noort V, Kunze R, Devos DP, Arumugam M, Bork P, Hurt E, "Insight into structure and assembly of the nuclear pore complex by utilizing the genome of a eukaryotic thermophile," Cell, 146: 277-289, 2011.

Andrulis ED, Neiman AM, Zappulla DC, Sternglanz R, "Perinuclear localization of chromatin facilitates transcriptional silencing," Nature, 394: 592-595, 1998.

Auffray C, Charron D, Hood L, "Predictive, preventive, personalized and participatory medicine: back to the future," Genome Med, 2: 57, 2010.

Auffray C, Hood L, "Editorial: Systems biology and personalized medicine - the future is now," Biotechnol J, 7: 938-939, 2012.

Avignon A, Standaert ML, Yamada K, Mischak H, Spencer B, Farese RV, "Insulin increases mRNA levels of protein kinase C-alpha and -beta in rat adipocytes and protein kinase C-alpha, -beta and -theta in rat skeletal muscle," The Biochemical journal, 308 ( Pt 1): 181-187, 1995.

Bansal M, Belcastro V, Ambesi-Impiombato A, di Bernardo D, "How to infer gene networks from expression profiles," Molecular systems biology, 3: 78, 2007.

Bardwell L, Cook JG, Zhu-Shimoni JX, Voora D, Thorner J, "Differential regulation of transcription: repression by unactivated mitogen-activated protein kinase Kss1 requires the Dig1 and Dig2 proteins," Proc Natl Acad Sci U S A, 95: 15400-15405, 1998.

Bermejo C, Garcia R, Straede A, Rodriguez-Pena JM, Nombela C, Heinisch JJ, Arroyo J, "Characterization of sensor-specific stress response by transcriptional profiling of wsc1 and mid2 deletion strains and chimeric sensors in Saccharomyces cerevisiae," OMICS, 14: 679-688, 2010.

Bodenmiller B, Wanka S, Kraft C, Urban J, Campbell D, Pedrioli PG, Gerrits B, Picotti P, Lam H, Vitek O, Brusniak MY, Roschitzki B, Zhang C, Shokat KM, Schlapbach R, Colman-Lerner A, Nolan GP, Nesvizhskii AI, Peter M, Loewith R et al., "Phosphoproteomic analysis reveals interconnected system-wide responses to perturbations of kinases and phosphatases in yeast," Sci Signal, 3: rs4, 2010.

Bousquet J, Anto JM, Sterk PJ, Adcock IM, Chung KF, Roca J, Agusti A, Brightling C, Cambon-Thomsen A, Cesario A, Abdelhak S, Antonarakis SE, Avignon A, Ballabio A, Baraldi E, Baranov A, Bieber T, Bockaert J, Brahmachari S, Brambilla C et al., "Systems medicine and integrated care to combat chronic noncommunicable diseases," Genome Med, 3: 43, 2011.

Bozdag S, Li A, Wuchty S, Fine HA, "FastMEDUSA: a parallelized tool to infer gene regulatory networks," Bioinformatics, 26: 1792-1793, 2010.

Breitkreutz A, Choi H, Sharom JR, Boucher L, Neduva V, Larsen B, Lin ZY, Breitkreutz BJ, Stark C, Liu G, Ahn J, Dewar-Darch D, Reguly T, Tang X, Almeida R, Qin ZS, Pawson T, Gingras AC, Nesvizhskii AI, Tyers M, "A global protein kinase and phosphatase interaction network in yeast," Science, 328: 1043-1046, 2010.

Brownlie RJ, Zamoyska R, "T cell receptor signalling networks: branched, diversified and bounded," Nat Rev Immunol, 13: 257-269, 2013.

Bullmore E, Sporns O, "Complex brain networks: graph theoretical analysis of structural and functional systems," Nat Rev Neurosci, 10: 186-198, 2009.

Butler J, MacCallum I, Kleber M, Shlyakhter IA, Belmonte MK, Lander ES, Nusbaum C, Jaffe DB, "ALLPATHS: de novo assembly of whole-genome shotgun microreads," Genome Res, 18: 810-820, 2008.

Cancer Genome Atlas N, "Comprehensive molecular portraits of human breast tumours. Nature, 490: 61-70, 2012.

Cancer Genome Atlas Research N, Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H, Robertson AG, Pashtan I, Shen R, Benz CC, Yau C, Laird PW, Ding L, Zhang W, Mills GB, Kucherlapati R, Mardis ER, Levine DA, "Integrated genomic characterization of endometrial carcinoma," Nature, 497: 67-73, 2013.

Chatr-aryamontri A, Ceol A, Palazzi LM, Nardelli G, Schneider MV, Castagnoli L, Cesareni G, "MINT: the Molecular INTeraction database," Nucleic Acids Res, 35: D572-574, 2007.

Chua G, Morris QD, Sopko R, Robinson MD, Ryan O, Chan ET, Frey BJ, Andrews BJ, Boone C, Hughes TR, "Identifying transcription factor functions and targets by phenotypic activation," Proceedings of the National Academy of Sciences of the United States of America, 103: 12045-12050, 2006.

Clarke J, Wu HC, Jayasinghe L, Patel A, Reid S, Bayley H, "Continuous base identification for single-molecule nanopore DNA sequencing," Nature nanotechnology, 4: 265-270, 2009.

Dalton S, "Signaling networks in human pluripotent stem cells," Curr Opin Cell Biol, 25: 241-246, 2013.

David L, Huber W, Granovskaia M, Toedling J, Palm CJ, Bofkin L, Jones T, Davis RW, Steinmetz LM, "A high-resolution map of transcription in the yeast genome," Proceedings of the National Academy of Sciences of the United States of America, 103: 5320-5325, 2006.

Dilworth DJ, Tackett AJ, Rogers RS, Yi EC, Christmas RH, Smith JJ, Siegel AF, Chait BT, Wozniak RW, Aitchison JD, "The mobile nucleoporin Nup2p and chromatin-bound Prp20p function in endogenous NPC-mediated transcriptional control," J Cell Biol, 171: 955-965, 2005.

Feuerbach F, Galy V, Trelles-Sticken E, Fromont-Racine M, Jacquier A, Gilson E, Olivo-Marin JC, Scherthan H, Nehrbass U, "Nuclear architecture and spatial positioning help establish transcriptional states of telomeres in yeast," Nat Cell Biol, 4: 214-221, 2002.

Fields S, Song O, "A novel genetic system to detect protein-protein interactions," Nature, 340: 245-246, 1989.

Freund Y, Mason L, "The alternating decision tree learning algorithm," Machine Learning, Proceedings: 124-133, 1999.

Galy V, Olivo-Marin JC, Scherthan H, Doye V, Rascalou N, Nehrbass U, "Nuclear pore complexes in the organization of silent telomeric chromatin," Nature, 403: 108-112, 2000.

Garcia R, Rodriguez-Pena JM, Bermejo C, Nombela C, Arroyo J, "The high osmotic response and cell wall integrity pathways cooperate to regulate transcriptional responses to zymolyase-induced cell wall stress in Saccharomyces cerevisiae," J Biol Chem, 284: 10901-10911, 2009.

Gasser SM, Hediger F, Taddei A, Neumann FR, Gartenberg MR, "The function of telomere clustering in yeast: the circe effect," Cold Spring Harb Symp Quant Biol, 69: 327-337, 2004.

Goonesekere NC, "Evaluating the efficacy of a structure-derived amino acid substitution matrix in detecting protein homologs by BLAST and PSI-BLAST," Adv Appl Bioinform Chem, 2: 71-78, 2009.

Gotta M, Laroche T, Formenton A, Maillet L, Scherthan H, Gasser SM, "The clustering of telomeres and colocalization with Rap1, Sir3, and Sir4 proteins in wild-type Saccharomyces cerevisiae," J Cell Biol, 134: 1349-1363, 1996.

Gotz J, Gladbach A, Pennanen L, van Eersel J, Schild A, David D, Ittner LM, "Animal models reveal role for tau phosphorylation in human disease," Biochim Biophys Acta, 1802: 860-871, 2010.

Guldener U, Munsterkotter M, Oesterheld M, Pagel P, Ruepp A, Mewes HW, Stumpflen V, "MPact: the MIPS protein interaction resource on yeast," Nucleic Acids Res, 34: D436-441, 2006.

Hao N, Yildirim N, Nagiec MJ, Parnell SC, Errede B, Dohlman HG, Elston TC, "Combined computational and experimental analysis reveals mitogen-activated protein kinase-mediated feedback phosphorylation as a mechanism for signaling specificity," Mol Biol Cell, 23: 3899-3910, 2012.

Hartley PD, Madhani HD, "Mechanisms that specify promoter nucleosome location and identity," Cell, 137: 445-458, 2009.

Hediger F, Dubrana K, Gasser SM, "Myosin-like proteins 1 and 2 are not required for silencing or telomere anchoring, but act in the Tel1 pathway of telomere length control," J Struct Biol, 140: 79-91, 2002a.

Hediger F, Neumann FR, Van Houwe G, Dubrana K, Gasser SM, "Live imaging of telomeres: yKu and Sir proteins define redundant telomere-anchoring pathways in yeast," Curr Biol, 12: 2076-2089, 2002b.

Herskovic JR, Tanaka LY, Hersh W, Bernstam EV, "A day in the life of PubMed: analysis of a typical day's query log," J Am Med Inform Assoc, 14: 212-220, 2007.

Hood L, "A personal journey of discovery: developing technology and changing biology," Annu Rev Anal Chem (Palo Alto Calif), 1: 1-43, 2008.

Hood L, Balling R, Auffray C, "Revolutionizing medicine in the 21st century through systems approaches," Biotechnol J, 7: 992-1001, 2012.

Hood L, Flores M, "A personal view on systems medicine and the emergence of proactive P4 medicine: predictive, preventive, personalized and participatory," N Biotechnol, 29: 613-624, 2012.

Hood L, Friend SH, "Predictive, personalized, preventive, participatory (P4) cancer medicine," Nat Rev Clin Oncol, 8: 184-187, 2011.

Hood L, Tian Q, "Systems approaches to biology and disease enable translational systems medicine," Genomics Proteomics Bioinformatics, 10: 181-185, 2012.

Ideker T, Thorsson V, Siegel AF, Hood LE, "Testing for differentially-expressed genes by maximum-likelihood analysis of microarray data," J Comput Biol, 7: 805-817, 2000.

Imming P, Sinning C, Meyer A, "Drugs, their targets and the nature and number of drug targets," Nat Rev Drug Discov, 5: 821-834, 2006.

Ingrell CR, Miller ML, Jensen ON, Blom N, "NetPhosYeast: prediction of protein phosphorylation sites in yeast," Bioinformatics, 23: 895-897, 2007.

Ishii K, Arib G, Lin C, Van Houwe G, Laemmli UK, "Chromatin boundaries in budding yeast: the nuclear pore connection," Cell, 109: 551-562, 2002.

Islamaj Dogan R, Murray GC, Neveol A, Lu Z, "Understanding PubMed user search behavior through log analysis," Database (Oxford), 2009: bap018, 2009.

Jaime MD, Lopez-Llorca LV, Conesa A, Lee AY, Proctor M, Heisler LE, Gebbia M, Giaever G, Westwood JT, Nislow C, "Identification of yeast genes that confer resistance to chitosan oligosaccharide (COS) using chemogenomics," BMC genomics, 13: 267, 2012.

Jeong H, Mason SP, Barabasi AL, Oltvai ZN, "Lethality and centrality in protein networks," Nature, 411: 41-42, 2001.

Kanehisa M, Goto S, "KEGG: kyoto encyclopedia of genes and genomes," Nucleic Acids Res, 28: 27-30, 2000.

Kehat I, Accornero F, Aronow BJ, Molkentin JD, "Modulation of chromatin position and gene expression by HDAC4 interaction with nucleoporins," J Cell Biol, 193: 21-29, 2011.

Kerrien S, Aranda B, Breuza L, Bridge A, Broackes-Carter F, Chen C, Duesbury M, Dumousseau M, Feuermann M, Hinz U, Jandrasits C, Jimenez RC, Khadake J, Mahadevan U, Masson P, Pedruzzi I, Pfeiffenberger E, Porras P, Raghunath A, Roechert B et al., "The IntAct molecular interaction database in 2012," Nucleic Acids Res, 40: D841-846, 2012.

Kerscher O, Hieter P, Winey M, Basrai MA, "Novel role for a Saccharomyces cerevisiae nucleoporin, Nup170p, in chromosome segregation," Genetics, 157: 1543-1553, 2001.

Khoury GA, Baliban RC, Floudas CA, "Proteome-wide post-translational modification statistics: frequency analysis and curation of the swiss-prot database," Sci Rep, 1, 2011.

Krzywinski M, Schein J, Birol I, Connors J, Gascoyne R, Horsman D, Jones SJ, Marra MA, "Circos: an information aesthetic for comparative genomics," Genome Res, 19: 1639-1645, 2009.

Kundaje A, Xin X, Lan C, Lianoglou S, Zhou M, Zhang L, Leslie C, "A predictive model of the oxygen and heme regulatory network in yeast," PLoS Comput Biol, 4: e1000224, 2008.

Kusari AB, Byon J, Bandyopadhyay D, Kenner KA, Kusari J, "Insulin-induced mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) attenuates insulin-stimulated MAP kinase activity: a mechanism for the feedback inhibition of insulin signaling," Mol Endocrinol, 11: 1532-1543, 1997.

Lee SH, Kim PJ, Jeong H, "Global organization of protein complexome in the yeast Saccharomyces cerevisiae," BMC systems biology, 5: 126, 2011a.

Lee TY, Bo-Kai Hsu J, Chang WC, Huang HD, "RegPhos: a system to explore the protein kinase-substrate phosphorylation network in humans," Nucleic Acids Res, 39: D777-787, 2011b.

Lopez-Garcia B, Gandia M, Munoz A, Carmona L, Marcos JF, "A genomic approach highlights common and diverse effects and determinants of susceptibility on the yeast Saccharomyces cerevisiae exposed to distinct antimicrobial peptides," BMC Microbiol, 10: 289, 2010.

Lu Z, Wilbur WJ, "Improving accuracy for identifying related PubMed queries by an integrated approach," J Biomed Inform, 42: 831-838, 2009.

Lu Z, Wilbur WJ, McEntyre JR, Iskhakov A, Szilagyi L, "Finding query suggestions for PubMed," AMIA Annu Symp Proc, 2009: 396-400, 2009a.

Lu Z, Xie N, Wilbur WJ, "Identifying related journals through log analysis," Bioinformatics, 25: 3038-3039, 2009b.

Margulies M, Egholm M, Altman WE, Attiya S, Bader JS, Bemben LA, Berka J, Braverman MS, Chen YJ, Chen Z, Dewell SB, Du L, Fierro JM, Gomes XV, Godwin BC, He W, Helgesen S, Ho CH, Irzyk GP, Jando SC et al., "Genome sequencing in microfabricated high-density picolitre reactors," Nature, 437: 376-380, 2005.

Mendjan S, Taipale M, Kind J, Holz H, Gebhardt P, Schelder M, Vermeulen M, Buscaino A, Duncan K, Mueller J, Wilm M, Stunnenberg HG, Saumweber H, Akhtar A, "Nuclear pore components are involved in the transcriptional regulation of dosage compensation in Drosophila," Molecular cell, 21: 811-823, 2006.

Minguez P, Parca L, Diella F, Mende DR, Kumar R, Helmer-Citterich M, Gavin AC, van Noort V, Bork P, "Deciphering a global network of functionally associated post-translational modifications," Mol Syst Biol, 8: 599, 2012.

Myers EW, Sutton GG, Delcher AL, Dew IM, Fasulo DP, Flanigan MJ, Kravitz SA, Mobarry CM, Reinert KH, Remington KA, Anson EL, Bolanos RA, Chou HH, Jordan CM, Halpern AL, Lonardi S, Beasley EM, Brandon RC, Chen L, Dunn PJ et al., "A whole-genome assembly of Drosophila," Science, 287: 2196-2204, 2000.

Nagalakshmi U, Wang Z, Waern K, Shou C, Raha D, Gerstein M, Snyder M, "The transcriptional landscape of the yeast genome defined by RNA sequencing," Science, 320: 1344-1349, 2008.

Neveol A, Islamaj Dogan R, Lu Z, "Semi-automatic semantic annotation of PubMed queries: a study on quality, efficiency, satisfaction," J Biomed Inform, 44: 310-318, 2011.

Praneenararat T, Takagi T, Iwasaki W, "Integration of interactive, multi-scale network navigation approach with Cytoscape for functional genomics in the big data era," BMC genomics, 13 Suppl 7: S24, 2012.

Prinz S, Avila-Campillo I, Aldridge C, Srinivasan A, Dimitrov K, Siegel AF, Galitski T, "Control of yeast filamentous-form growth by modules in an integrated molecular network," Genome Res, 14: 380-390, 2004.

Proft M, Pascual-Ahuir A, de Nadal E, Arino J, Serrano R, Posas F, "Regulation of the Sko1 transcriptional repressor by the Hog1 MAP kinase in response to osmotic stress," EMBO J, 20: 1123-1133, 2001.

Proulx SR, Promislow DE, Phillips PC, "Network thinking in ecology and evolution," Trends Ecol Evol, 20: 345-353, 2005.

Ratnakumar S, Young ET, "Snf1 dependence of peroxisomal gene expression is mediated by Adr1," The Journal of biological chemistry, 285: 10703-10714, 2010.

Roberts CJ, Nelson B, Marton MJ, Stoughton R, Meyer MR, Bennett HA, He YD, Dai H, Walker WL, Hughes TR, Tyers M, Boone C, Friend SH, "Signaling and circuitry of multiple MAPK pathways revealed by a matrix of global gene expression profiles," Science, 287: 873-880, 2000.

Rodriguez-Quinones JF, Rodriguez-Medina JR, "Differential gene expression signatures for cell wall integrity found in chitin synthase II (chs2Delta) and myosin II (myo1Delta) deficient cytokinesis mutants of Saccharomyces cerevisiae," BMC Res Notes, 2: 87, 2009.

Rothberg JM, Hinz W, Rearick TM, Schultz J, Mileski W, Davey M, Leamon JH, Johnson K, Milgrew MJ, Edwards M, Hoon J, Simons JF, Marran D, Myers JW, Davidson JF, Branting A, Nobile JR, Puc BP, Light D, Clark TA et al., "An integrated semiconductor device enabling non-optical genome sequencing," Nature, 475: 348-352, 2011.

Rout MP, Aitchison JD, Suprapto A, Hjertaas K, Zhao Y, Chait BT, "The yeast nuclear pore complex: composition, architecture, and transport mechanism," J Cell Biol, 148: 635-651, 2000.

Sabbagh W, Jr., Flatauer LJ, Bardwell AJ, Bardwell L, "Specificity of MAP kinase signaling in yeast differentiation involves transient versus sustained MAPK activation," Molecular cell, 8: 683-691, 2001.

Sackmann A, Heiner M, Koch I, "Application of Petri net based analysis techniques to signal transduction pathways," BMC Bioinformatics, 7: 482, 2006.

Sanz AB, Garcia R, Rodriguez-Pena JM, Diez-Muniz S, Nombela C, Peterson CL, Arroyo J, "Chromatin remodeling by the SWI/SNF complex is essential for transcription mediated by the yeast cell wall integrity MAPK pathway," Mol Biol Cell, 23: 2805-2817, 2012.

Schroeder MP, Gonzalez-Perez A, Lopez-Bigas N, "Visualizing multidimensional cancer genomics data," Genome Med, 5: 9, 2013.

Schwartz MA, Madhani HD, "Principles of MAP kinase signaling specificity in Saccharomyces cerevisiae," Annual review of genetics, 38: 725-748, 2004.

Sharan R, Ideker T, "Modeling cellular machinery through biological network comparison," Nat Biotechnol, 24: 427-433, 2006.

Sharan R, Suthram S, Kelley RM, Kuhn T, McCuine S, Uetz P, Sittler T, Karp RM, Ideker T, "Conserved patterns of protein interaction in multiple species," Proceedings of the National Academy of Sciences of the United States of America, 102: 1974-1979, 2005.

Shivaswamy S, Bhinge A, Zhao Y, Jones S, Hirst M, Iyer VR, "Dynamic remodeling of individual nucleosomes across a eukaryotic genome in response to transcriptional perturbation," PLoS Biol, 6: e65, 2008.

Shock TR, Thompson J, Yates JR, 3rd, Madhani HD, "Hog1 mitogen-activated protein kinase (MAPK) interrupts signal transduction between the Kss1 MAPK and the Tec1 transcription factor to maintain pathway specificity," Eukaryot Cell, 8: 606-616, 2009.

Simpson JT, Wong K, Jackman SD, Schein JE, Jones SJ, Birol I, "ABySS: a parallel assembler for short read sequence data," Genome Res, 19: 1117-1123, 2009.

Smith JJ, Marelli M, Christmas RH, Vizeacoumar FJ, Dilworth DJ, Ideker T, Galitski T, Dimitrov K, Rachubinski RA, Aitchison JD, "Transcriptome profiling to identify genes involved in peroxisome assembly and function," J Cell Biol, 158: 259-271, 2002.

Smith JJ, Ramsey SA, Marelli M, Marzolf B, Hwang D, Saleem RA, Rachubinski RA, Aitchison JD, "Transcriptional responses to fatty acid are coordinated by combinatorial control," Molecular systems biology, 3: 115, 2007.

Stark C, Breitkreutz BJ, Chatr-Aryamontri A, Boucher L, Oughtred R, Livstone MS, Nixon J, Van Auken K, Wang X, Shi X, Reguly T, Rust JM, Winter A, Dolinski K, Tyers M, "The BioGRID Interaction Database: 2011 update," Nucleic Acids Res, 39: D698-704, 2011.

Stark C, Su TC, Breitkreutz A, Lourenco P, Dahabieh M, Breitkreutz BJ, Tyers M, Sadowski I, "PhosphoGRID: a database of experimentally verified in vivo protein phosphorylation sites from the budding yeast Saccharomyces cerevisiae," Database (Oxford), 2010: bap026, 2010.

Stephan KE, Hilgetag CC, Burns GA, O'Neill MA, Young MP, Kotter R, "Computational analysis of functional connectivity between areas of primate cerebral cortex," Philos Trans R Soc Lond B Biol Sci, 355: 111-126, 2000.

Szklarczyk D, Franceschini A, Kuhn M, Simonovic M, Roth A, Minguez P, Doerks T, Stark M, Muller J, Bork P, Jensen LJ, von Mering C, "The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored," Nucleic Acids Res, 39: D561-568, 2011.

Taddei A, Schober H, Gasser SM, "The budding yeast nucleus," Cold Spring Harb Perspect Biol, 2: a000612, 2010.

Therizols P, Fairhead C, Cabal GG, Genovesio A, Olivo-Marin JC, Dujon B, Fabre E, "Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region," J Cell Biol, 172: 189-199, 2006.

Tian Q, Price ND, Hood L, "Systems cancer medicine: towards realization of predictive, preventive, personalized and participatory (P4) medicine," J Intern Med, 271: 111-121, 2012.

Turinsky AL, Razick S, Turner B, Donaldson IM, Wodak SJ, "Literature curation of protein interactions: measuring agreement across major public databases," Database (Oxford), 2010: baq026, 2010.

van Berlo JH, Elrod JW, Aronow BJ, Pu WT, Molkentin JD, "Serine 105 phosphorylation of transcription factor GATA4 is necessary for stress-induced cardiac hypertrophy in vivo," Proc Natl Acad Sci U S A, 108: 12331-12336, 2011.

Van de Vosse DW, Wan Y, Lapetina DL, Chen WM, Chiang JH, Aitchison JD, Wozniak RW, "A role for the nucleoporin Nup170p in chromatin structure and gene silencing," Cell, 152: 969-983, 2013.

Van de Vosse DW, Wan Y, Wozniak RW, Aitchison JD, "Role of the nuclear envelope in genome organization and gene expression," Wiley Interdiscip Rev Syst Biol Med, 3: 147-166, 2011.

van Wageningen S, Kemmeren P, Lijnzaad P, Margaritis T, Benschop JJ, de Castro IJ, van Leenen D, Groot Koerkamp MJ, Ko CW, Miles AJ, Brabers N, Brok MO, Lenstra TL, Fiedler D, Fokkens L, Aldecoa R, Apweiler E, Taliadouros V, Sameith K, van de Pasch LA et al, "Functional overlap and regulatory links shape genetic interactions between signaling pathways," Cell, 143: 991-1004, 2010.

Vaquerizas JM, Kummerfeld SK, Teichmann SA, Luscombe NM, "A census of human transcription factors: function, expression and evolution," Nat Rev Genet, 10: 252-263, 2009.

Verma-Gaur J, Rao SN, Taya T, Sadhale P, "Genomewide recruitment analysis of Rpb4, a subunit of polymerase II in Saccharomyces cerevisiae, reveals its involvement in transcription elongation," Eukaryotic cell, 7: 1009-1018, 2008.

Wan Y, Chen W, Xing J, Tan J, Li B, Chen H, Lin Z, Chiang JH, Saleem RA, "Transcriptome profiling reveals a novel role for trichostatin A in antagonizing histone chaperone Chz1 mediated telomere anti-silencing," FEBS Lett, 585: 2519-2525, 2011.

Wan Y, Chiang JH, Lin CH, Arens CE, Saleem RA, Smith JJ, Aitchison JD, "Histone chaperone Chz1p regulates H2B ubiquitination and subtelomeric anti-silencing," Nucleic Acids Res, 38: 1431-1440, 2010.

Wan Y, Saleem RA, Ratushny AV, Roda O, Smith JJ, Lin CH, Chiang JH, Aitchison JD, "Role of the histone variant H2A.Z/Htz1p in TBP recruitment, chromatin dynamics, and regulated expression of oleate-responsive genes," Mol Cell Biol, 29: 2346-2358, 2009.

Wang L, Hou L, Qian M, Deng M, "Integrating phosphorylation network with transcriptional network reveals novel functional relationships," PLoS One, 7: e33160, 2012.

Watanabe Y, Irie K, Matsumoto K, "Yeast RLM1 encodes a serum response factor-like protein that may function downstream of the Mpk1 (Slt2) mitogen-activated protein kinase pathway," Mol Cell Biol, 15: 5740-5749, 1995.

Way JC, Silver PA, "Systems engineering without an engineer : Why we need systems biology," Complexity, 13: 22-29, 2007.

Weiner A, Hughes A, Yassour M, Rando OJ, Friedman N, "High-resolution nucleosome mapping reveals transcription-dependent promoter packaging," Genome Res, 20: 90-100, 2010.

Xu Z, Wei W, Gagneur J, Perocchi F, Clauder-Munster S, Camblong J, Guffanti E, Stutz F, Huber W, Steinmetz LM, "Bidirectional promoters generate pervasive transcription in yeast," Nature, 457: 1033-1037, 2009.

Xue Y, Ren J, Gao X, Jin C, Wen L, Yao X, "GPS 2.0, a tool to predict kinase-specific phosphorylation sites in hierarchy," Mol Cell Proteomics, 7: 1598-1608, 2008.

Yang D, Khan S, Sun Y, Hess K, Shmulevich I, Sood AK, Zhang W, "Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer," JAMA : the journal of the American Medical Association, 306: 1557-1565, 2011.

Yang D, Sun Y, Hu L, Zheng H, Ji P, Pecot CV, Zhao Y, Reynolds S, Cheng H, Rupaimoole R, Cogdell D, Nykter M, Broaddus R, Rodriguez-Aguayo C, Lopez-Berestein G, Liu J, Shmulevich I, Sood AK, Chen K, Zhang W, "Integrated analyses identify a master microRNA regulatory network for the mesenchymal subtype in serous ovarian cancer," Cancer cell, 23: 186-199, 2013a.

Yang SH, Sharrocks AD, Whitmarsh AJ, "MAP kinase signalling cascades and transcriptional regulation," Gene, 513: 1-13, 2013b.

Yuan GC, Liu YJ, Dion MF, Slack MD, Wu LF, Altschuler SJ, Rando OJ, "Genome-scale identification of nucleosome positions in S. cerevisiae," Science, 309: 626-630, 2005.

Zerbino DR, Birney E, "Velvet: algorithms for de novo short read assembly using de Bruijn graphs," Genome Res, 18: 821-829, 2008.
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