{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:24:12Z","timestamp":1775694252940,"version":"3.50.1"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"S2","license":[{"start":{"date-parts":[[2010,9,1]],"date-time":"2010-09-01T00:00:00Z","timestamp":1283299200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BMC Syst Biol"],"published-print":{"date-parts":[[2010,9]]},"DOI":"10.1186\/1752-0509-4-s2-s7","type":"journal-article","created":{"date-parts":[[2010,9,14]],"date-time":"2010-09-14T06:16:04Z","timestamp":1284444964000},"source":"Crossref","is-referenced-by-count":50,"title":["A systems biology approach to identify effective cocktail drugs"],"prefix":"10.1186","volume":"4","author":[{"given":"Zikai","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing-Ming","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luonan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2010,9,13]]},"reference":[{"key":"537_CR1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470488065","volume-title":"Biomolecular Networks: Methods and Applications in Systems Biology","author":"LN Chen","year":"2009","unstructured":"Chen LN, Wang RS, Zhang XS: Biomolecular Networks: Methods and Applications in Systems Biology. 2009, New Jersey, USA: Wiley Interscience"},{"key":"537_CR2","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1038\/nrd1202","volume":"2","author":"MA Lindsay","year":"2003","unstructured":"Lindsay MA: Target discovery. Nat Rev Drug Discov. 2003, 2: 831-838. 10.1038\/nrd1202","journal-title":"Nat Rev Drug Discov"},{"key":"537_CR3","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1038\/msb.2008.60","volume":"4","author":"K Yang","year":"2008","unstructured":"Yang K, Bai HJ, Ouyang Q, Lai LH, Tang C: Finding multiple traget optimal intervention in disease-related molecular network. Molecular Systems Biology. 2008, 4: 228- 10.1038\/msb.2008.60","journal-title":"Molecular Systems Biology"},{"issue":"3","key":"537_CR4","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1124\/pr.58.3.10","volume":"58","author":"TC Chou","year":"2006","unstructured":"Chou TC: Theoretical Basis, Experimental Design, and Computerized Simulation of Synergism and Antagonism in Drug Combination Studies. Pharmacol Rev. 2006, 58 (3): 621-680. 10.1124\/pr.58.3.10","journal-title":"Pharmacol Rev"},{"key":"537_CR5","first-page":"285","volume":"3","author":"S Loewe","year":"1953","unstructured":"Loewe S: The problem of synergism and antagonism of combined drugs. Arzneimittelforschung. 1953, 3: 285-290.","journal-title":"Arzneimittelforschung"},{"issue":"9","key":"537_CR6","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1038\/nchembio817","volume":"2","author":"JB Fitzgerald","year":"2006","unstructured":"Fitzgerald JB, Schoeberl B, Nielsen UB, orger PK: Systems biology and combination therapy in the quest for clinical efficacy. Nat Chem Bioc. 2006, 2 (9): 458-466. 10.1038\/nchembio817.","journal-title":"Nat Chem Bioc"},{"key":"537_CR7","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1128\/MMBR.20.4.243-258.1956","volume":"20","author":"CI Bliss","year":"1956","unstructured":"Bliss CI: The calculation of microbial assays. Bacteriol Rev. 1956, 20: 243-258.","journal-title":"Bacteriol Rev"},{"issue":"10","key":"537_CR8","doi-asserted-by":"publisher","first-page":"3777","DOI":"10.1073\/pnas.0500055102","volume":"102","author":"N Agrawal","year":"2005","unstructured":"Agrawal N, Pallos J, Slepko N, Apostol BL, Bodai L, Chang LW, Chiang AS: Thompson LM, Marsh JL, Identification of combinatorial drug combination regimens for treatment of Huntington's disease using Drosophila. Proc Natl Acad Sci. 2005, 102 (10): 3777-3781. 10.1073\/pnas.0500055102","journal-title":"Proc Natl Acad Sci"},{"issue":"12","key":"537_CR9","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/j.tibtech.2007.09.004","volume":"25","author":"G Cottarel","year":"2007","unstructured":"Cottarel G, Wierzbowski J: Combination drugs, an emerging option for antibacterial therapy. TRENDS Biotechnol. 2007, 25 (12): 548-554. 10.1016\/j.tibtech.2007.09.004.","journal-title":"TRENDS Biotechnol"},{"issue":"12","key":"537_CR10","doi-asserted-by":"publisher","first-page":"e1000249","DOI":"10.1371\/journal.pcbi.1000249","volume":"4","author":"D Calzolari","year":"2008","unstructured":"Calzolari D, Bruschi S, Coquin L, Schofield J, Feala J, Reed JC, McCulloch AD: Paternostro G, Search Algorithms as a framework for the Optimization of Drug combinations. Plos Comput Biol. 2008, 4 (12): e1000249- 10.1371\/journal.pcbi.1000249","journal-title":"Plos Comput Biol"},{"issue":"13","key":"537_CR11","doi-asserted-by":"publisher","first-page":"7977","DOI":"10.1073\/pnas.1337088100","volume":"100","author":"AA Borisy","year":"2003","unstructured":"Borisy AA, Elliott PJ, Hurst NW, Lee MS, Leh\u00e1l J, Price ER, Serbedzija G, Zimmermann GR, Foley MA, Stockwell BR, Keith CT: Systematic discovery of multicomponent therapeutics. Proc Natl Acad Sci. 2003, 100 (13): 7977-7982. 10.1073\/pnas.1337088100","journal-title":"Proc Natl Acad Sci"},{"issue":"13","key":"537_CR12","doi-asserted-by":"publisher","first-page":"5105","DOI":"10.1073\/pnas.0800823105","volume":"105","author":"PK Wong","year":"2008","unstructured":"Wong PK, Yu FQ, Shahangian A, Cheng GH, Sun R, Ho CM: Closed-loop control of cellular functions using comninatory drugs guided by a stochastic search algorithm. Proc Natl Acad Sci. 2008, 105 (13): 5105-5110. 10.1073\/pnas.0800823105","journal-title":"Proc Natl Acad Sci"},{"key":"537_CR13","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/1752-0509-3-81","volume":"3","author":"A Vazquez","year":"2009","unstructured":"Vazquez A: Optimal drug combinations and minimal hitting sets. BMC Systems Biology. 2009, 3: 81- 10.1186\/1752-0509-3-81","journal-title":"BMC Systems Biology"},{"key":"537_CR14","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.arcmed.2005.03.004","volume":"36","author":"T Maria","year":"2005","unstructured":"Maria T, Tusi\u00e9 L: Genes and Type 2 diabetes Mellitus. Arch Med Res. 2005, 36: 210-222. 10.1016\/j.arcmed.2005.03.004","journal-title":"Arch Med Res"},{"key":"537_CR15","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1001\/jama.283.13.1695","volume":"283","author":"V Fonseca","year":"2000","unstructured":"Fonseca V, Rosenstock J, Patwardhan , Salzman A: Effect of Metformin and Rosiglitazone Combination Therapy in Patients with Type 2 Diabetes Mellitus(A Randomized Controlled Trial). The Journal of the American Medical Association. 2000, 283: 1695-1702. 10.1001\/jama.283.13.1695.","journal-title":"The Journal of the American Medical Association"},{"key":"537_CR16","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1002\/dmrr.264","volume":"18","author":"F G\u00f3mez-Perez","year":"2002","unstructured":"G\u00f3mez-Perez F, Fangh\u00e4nel-Salm\u00f3n G, Barbosa JA, Montes-Villareal J, Berry RA, Warsi G, Gould EM: Efficacy and safety of Rosiglitazone plus Metformin in Mexicans with type 2 diabetes. Diabetes Metab rev. 2002, 18: 127-134. 10.1002\/dmrr.264.","journal-title":"Diabetes Metab rev"},{"issue":"9","key":"537_CR17","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1111\/j.1742-1241.2004.00318.x","volume":"58","author":"CJ Bailey","year":"2004","unstructured":"Bailey CJ, Day C: Avandamet: combined Metformin-Rosiglitazone treatment for insulin resistence in type 2 diabetes. Int J Clin Pract. 2004, 58 (9): 867-876. 10.1111\/j.1742-1241.2004.00318.x","journal-title":"Int J Clin Pract"},{"issue":"10","key":"537_CR18","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1111\/j.1368-5031.2005.00652.x","volume":"59","author":"C Rosak","year":"2005","unstructured":"Rosak C, Petzoldt R, Wolf R, Reblin T, Dehmel B, Seidel D: Rosliglitazone plus Metformin is effective and well telerated in clinical practice: results from large observational studies in people with type 2 diabetes. Int J Clin Pract. 2005, 59 (10): 1131-1136. 10.1111\/j.1368-5031.2005.00652.x","journal-title":"Int J Clin Pract"},{"key":"537_CR19","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1111\/j.1463-1326.2006.00659.x","volume":"8","author":"J Rosenstock","year":"2006","unstructured":"Rosenstock J, Rood J, Cobitz A, Biswas N, Chou H, Garber A: Initial treatment with Rosiglitazone\/Metformin fixed-dose combination therapy compared with monotherapy with either Rosiglitazone or Metformin in patients with uncontrolled type 2 diabetes. Diabetes Obes Metab. 2006, 8: 650-660. 10.1111\/j.1463-1326.2006.00659.x","journal-title":"Diabetes Obes Metab"},{"key":"537_CR20","doi-asserted-by":"publisher","first-page":"D514","DOI":"10.1093\/nar\/gki033","volume":"33","author":"A Hamosh","year":"2005","unstructured":"Hamosh A, Scott AF, Amberger JS, Bocchini CA, McKusick VA: Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res. 2005, 33: D514-D517. 10.1093\/nar\/gki033","journal-title":"Nucleic Acids Res"},{"key":"537_CR21","doi-asserted-by":"publisher","first-page":"D793","DOI":"10.1093\/nar\/gkn665","volume":"37","author":"J Amberger","year":"2009","unstructured":"Amberger J, Bocchini CA, Scott AF, Hamosh A: McKusick's Online Mendelian Inheritance in Man (OMIMR). Nucleic Acids Res. 2009, 37: D793-D796. 10.1093\/nar\/gkn665","journal-title":"Nucleic Acids Res"},{"issue":"10","key":"537_CR22","doi-asserted-by":"publisher","first-page":"3067","DOI":"10.1093\/nar\/gkl381","volume":"34","author":"N Tiffin","year":"2006","unstructured":"Tiffin N, Adie E, Turner F, Brunner HG, Van DMA, Oti M, Lopez-Bigas N, Ouzounis C, Perez-Iratxeta C, Andrade-Navarro MA: Computational disease gene identification: a concert of methods prioritizes type 2 diabetes and obesity candidate genes. Nucleic Acids Res. 2006, 34 (10): 3067-3081. 10.1093\/nar\/gkl381","journal-title":"Nucleic Acids Res"},{"key":"537_CR23","doi-asserted-by":"publisher","first-page":"D258","DOI":"10.1093\/nar\/gkh066","volume":"32","author":"MA Harris","year":"2004","unstructured":"Harris MA: The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res. 2004, 32: D258-D261. 10.1093\/nar\/gkh066","journal-title":"Nucleic Acids Res"},{"key":"537_CR24","doi-asserted-by":"publisher","first-page":"D277","DOI":"10.1093\/nar\/gkh063","volume":"32","author":"M Kanehisa","year":"2004","unstructured":"Kanehisa M, Goto S, Kawashima S, Okuno Y, Hattori M: The KEGG resource for deciphering the genome. Nucleic Acids Res. 2004, 32: D277-D280. 10.1093\/nar\/gkh063","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"537_CR25","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nprot.2008.211","volume":"4","author":"DW Huang","year":"2009","unstructured":"Huang DW, Sherman BT, Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID Bioinformatics Resources. Nat Protoc. 2009, 4 (1): 44-57. 10.1038\/nprot.2008.211","journal-title":"Nat Protoc"},{"key":"537_CR26","volume-title":"Experimental Diabetes Research","author":"SH Lee","year":"2009","unstructured":"Lee SH, Demeterco C, Geron I, Abrahamsson A, Levine F, Itkin-Ansari P: Islet SpecificWnt Activation in Human Type II Diabetes. Experimental Diabetes Research. 2009, 2009:doi:10.1155\/2008\/728763"},{"key":"537_CR27","doi-asserted-by":"publisher","first-page":"D668","DOI":"10.1093\/nar\/gkj067","volume":"34","author":"DS Wishart","year":"2006","unstructured":"Wishart DS, Knox C, Guo AC, Shrivastava S, Hassanali M, Stothard P, Chang Z, Woolsey J: DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res. 2006, 34: D668-D672. 10.1093\/nar\/gkj067","journal-title":"Nucleic Acids Res"},{"key":"537_CR28","doi-asserted-by":"publisher","first-page":"D901","DOI":"10.1093\/nar\/gkm958","volume":"36","author":"DS Wishart","year":"2008","unstructured":"Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008, 36: D901-D906. 10.1093\/nar\/gkm958","journal-title":"Nucleic Acids Res"},{"key":"537_CR29","doi-asserted-by":"publisher","first-page":"D103","DOI":"10.1093\/nar\/gki004","volume":"33","author":"F Zhao","year":"2005","unstructured":"Zhao F, Xuan Z, Liu L, Zhang MQ: TRED: a Transcriptional Regulatory Element Database and a platform for in silico gene regulation studies. Nucleic Acids Res. 2005, 33: D103-D107. 10.1093\/nar\/gki004","journal-title":"Nucleic Acids Res"},{"key":"537_CR30","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1038\/msb4100089","volume":"2","author":"Q Cui","year":"2006","unstructured":"Cui Q, Yu Z, Purisima EO, Wang E: Principles of microRNA regulation of a human cellular signaling network. Molecular Systems Biology. 2006, 2: 46- 10.1038\/msb4100089","journal-title":"Molecular Systems Biology"},{"issue":"1","key":"537_CR31","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/nar\/30.1.207","volume":"30","author":"R Edgar","year":"2002","unstructured":"Edgar R, Domrachev M, Lash AE: Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 2002, 30 (1): 207-210. 10.1093\/nar\/30.1.207","journal-title":"Nucleic Acids Res"},{"key":"537_CR32","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1093\/nar\/gkl887","volume":"35","author":"TY Barrett","year":"2002","unstructured":"Barrett TY, Troup DB, Wilhite SE, Ledoux P, Rudnev D, Evangelista C, Kim IF, Soboleva A, Tomashevsky M, Edgar R: NCBI GEO: mining tens of millions of expression profiles-database and tools update. Nucleic Acids Res. 2002, 35: 760-765. 10.1093\/nar\/gkl887.","journal-title":"Nucleic Acids Res"},{"issue":"29","key":"537_CR33","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1126\/science.1132939","volume":"313","author":"J Lamb","year":"2006","unstructured":"Lamb J, Crawford ED, Peck D, Modell JW, Blat IC, Wrobel MJ, Lerner J, Brunet JP, Subramanian A, Ross KN, et al.: The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes and Disease. Science. 2006, 313 (29): 1929-1935. 10.1126\/science.1132939","journal-title":"Science"},{"key":"537_CR34","doi-asserted-by":"publisher","first-page":"2121","DOI":"10.1093\/bioinformatics\/btm294","volume":"23","author":"Z Guo","year":"2007","unstructured":"Guo Z, Li Y, Gong X, Yao C, Ma W, Wang D, Li Y, Zhu J, Zhang M, Yang D, Wang J: Edge-based scoring and searching method for identifying condition-responsive protein-protein interaction sub-network. Bioinformatics. 2007, 23: 2121-2128. 10.1093\/bioinformatics\/btm294","journal-title":"Bioinformatics"},{"key":"537_CR35","doi-asserted-by":"publisher","first-page":"e96","DOI":"10.1371\/journal.pgen.0030096","volume":"3","author":"M Liu","year":"2007","unstructured":"Liu M, Liberzon A, Kong SW, Lai WR, Park PJ, Kohane IS, Kasif S: Network-Based Analysis of Affected Biological Processes in Type 2 Diabetes Models. PLOS Genet. 2007, 3: e96- 10.1371\/journal.pgen.0030096","journal-title":"PLOS Genet"},{"key":"537_CR36","doi-asserted-by":"publisher","first-page":"2792","DOI":"10.1093\/bioinformatics\/btn499","volume":"24","author":"J Noisel","year":"2008","unstructured":"Noisel J, Sanguinetti G, Wright P: Identifying differentially-expressed subnetworks with MMG. Bioinformatics. 2008, 24: 2792-2793. 10.1093\/bioinformatics\/btn499","journal-title":"Bioinformatics"},{"key":"537_CR37","doi-asserted-by":"publisher","first-page":"i223","DOI":"10.1093\/bioinformatics\/btn161","volume":"24","author":"M Dittrich","year":"2008","unstructured":"Dittrich M, Klau G, Rosenwald A, Dandekarand T, Muller T: Identifying functional modules in protein-protein interaction networks: an integrated exact approach. Bioinformatics. 2008, 24: i223-i231. 10.1093\/bioinformatics\/btn161","journal-title":"Bioinformatics"},{"key":"537_CR38","first-page":"347","volume":"4955","author":"I Ulitsky","year":"2008","unstructured":"Ulitsky I, Karp M, Shamir R: Detecting Disease-Specific Dysregulated Pathways Via Analysis of Clinical Expression Profiles. Lect N Bioinformat(RECOMB2008). 2008, 4955: 347-359.","journal-title":"Lect N Bioinformat(RECOMB2008)"},{"issue":"6","key":"537_CR39","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1049\/iet-syb.2008.0155","volume":"3","author":"YQ Qiu","year":"2009","unstructured":"Qiu YQ, Zhang SH, Zhang XS, Chen LN: Identifying differentially expressed pathways via a mixed integer linear programming model. IET Systems Biology. 2009, 3 (6): 475-486. 10.1049\/iet-syb.2008.0155","journal-title":"IET Systems Biology"},{"issue":"2","key":"537_CR40","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1142\/S0219720009004138","volume":"7","author":"XM Zhao","year":"2009","unstructured":"Zhao XM, Wang RS, Chen LN, Aihara K: Automatic modeling of signaling pathways based on network flow model. Journal of Bioinformatics and Computational Biology. 2009, 7 (2): 309-322. 10.1142\/S0219720009004138","journal-title":"Journal of Bioinformatics and Computational Biology"},{"issue":"9","key":"537_CR41","doi-asserted-by":"publisher","first-page":"e48","DOI":"10.1093\/nar\/gkn145","volume":"36","author":"XM Zhao","year":"2008","unstructured":"Zhao XM, Wang RS, Chen L, Aihara K: Uncovering signal transduction networks from high-throughput data by integer linear programming. Nucl. Acids Res. 2008, 36 (9): e48- 10.1093\/nar\/gkn145","journal-title":"Nucl. Acids Res"},{"issue":"3","key":"537_CR42","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/s10059-009-0035-x","volume":"27","author":"Z Wu","year":"2009","unstructured":"Wu Z, Zhao X, Chen L: Identifying responsive functional modules from protein-protein interaction network. Molecules and Cells. 2009, 27 (3): 271-277. 10.1007\/s10059-009-0035-x","journal-title":"Molecules and Cells"},{"key":"537_CR43","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1002\/(SICI)1520-6750(199610)43:7<985::AID-NAV4>3.0.CO;2-9","volume":"43","author":"HF Lee","year":"1996","unstructured":"Lee HF, Dooly DR: Algorithms for the constrained maximum-Weight connected graph problem. Nav Res Log. 1996, 43: 985-1008. 10.1002\/(SICI)1520-6750(199610)43:7<985::AID-NAV4>3.0.CO;2-9.","journal-title":"Nav Res Log"}],"container-title":["BMC Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-4-S2-S7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1752-0509-4-S2-S7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-4-S2-S7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,6,11]],"date-time":"2020-06-11T16:43:41Z","timestamp":1591893821000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcsystbiol.biomedcentral.com\/articles\/10.1186\/1752-0509-4-S2-S7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,9]]},"references-count":43,"journal-issue":{"issue":"S2","published-print":{"date-parts":[[2010,9]]}},"alternative-id":["537"],"URL":"https:\/\/doi.org\/10.1186\/1752-0509-4-s2-s7","relation":{},"ISSN":["1752-0509"],"issn-type":[{"value":"1752-0509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,9]]},"article-number":"S7"}}