{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T17:00:54Z","timestamp":1765040454752},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Syst Biol"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cellular differentiation and reprogramming are processes that are carefully orchestrated by the activation and repression of specific sets of genes. An increasing amount of experimental results show that despite the large number of genes participating in transcriptional programs of cellular phenotypes, only few key genes, which are coined here as reprogramming determinants, are required to be directly perturbed in order to induce cellular reprogramming. However, identification of reprogramming determinants still remains a combinatorial problem, and the state-of-art methods addressing this issue rests on exhaustive experimentation or prior knowledge to narrow down the list of candidates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here we present a computational method, without any preliminary selection of candidate genes, to identify reduced subsets of genes, which when perturbed can induce transitions between cellular phenotypes. The method relies on the expression profiles of two stable cellular phenotypes along with a topological analysis stability elements in the gene regulatory network that are necessary to cause this multi-stability. Since stable cellular phenotypes can be considered as attractors of gene regulatory networks, cell fate and cellular reprogramming involves transition between these attractors, and therefore current method searches for combinations of genes that are able to destabilize a specific initial attractor and stabilize the final one in response to the appropriate perturbations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The method presented here represents a useful framework to assist researchers in the field of cellular reprogramming to design experimental strategies with potential applications in the regenerative medicine and disease modelling.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1752-0509-7-140","type":"journal-article","created":{"date-parts":[[2013,12,19]],"date-time":"2013-12-19T02:02:20Z","timestamp":1387418540000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Detecting cellular reprogramming determinants by differential stability analysis of gene regulatory networks"],"prefix":"10.1186","volume":"7","author":[{"given":"Isaac","family":"Crespo","sequence":"first","affiliation":[]},{"given":"Thanneer M","family":"Perumal","sequence":"additional","affiliation":[]},{"given":"Wiktor","family":"Jurkowski","sequence":"additional","affiliation":[]},{"given":"Antonio","family":"del Sol","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2013,12,19]]},"reference":[{"key":"1255_CR1","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/0022-5193(69)90015-0","volume":"22","author":"SA Kauffman","year":"1969","unstructured":"Kauffman SA: Metabolic stability and epigenetics in randomly constructed genetics nets. J Theor Biol. 1969, 22: 437-467. 10.1016\/0022-5193(69)90015-0.","journal-title":"J Theor Biol"},{"key":"1255_CR2","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780195079517.001.0001","volume-title":"The origins of order: self organization and selection in evolutions","author":"SA Kauffman","year":"1993","unstructured":"Kauffman SA: The origins of order: self organization and selection in evolutions. 1993, New York: Oxford UniversityPress"},{"issue":"12","key":"1255_CR3","doi-asserted-by":"publisher","first-page":"128701","DOI":"10.1103\/PhysRevLett.94.128701","volume":"94","author":"S Huang","year":"2005","unstructured":"Huang S, Eichler G, Bar-Yam Y, Ingber DE: Cell fates as high-dimensional attractor states of a complex gene regulatory network. Phys Rev Lett. 2005, 94 (12): 128701-","journal-title":"Phys Rev Lett"},{"issue":"7356","key":"1255_CR4","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1038\/nature10116","volume":"475","author":"P Huang","year":"2011","unstructured":"Huang P, He Z, Ji S, Sun H, Xiang D, Liu C, Hu Y, Wang X, Hui L: Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature. 2011, 475 (7356): 386-389. 10.1038\/nature10116.","journal-title":"Nature"},{"issue":"3","key":"1255_CR5","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.cell.2010.07.002","volume":"142","author":"M Ieda","year":"2010","unstructured":"Ieda M, Fu JD, Delgado-Olguin P, Vedantham V, Hayashi Y, Bruneau BG, Srivastava D: Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell. 2010, 142 (3): 375-386. 10.1016\/j.cell.2010.07.002.","journal-title":"Cell"},{"issue":"6","key":"1255_CR6","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/S0092-8674(00)80702-3","volume":"100","author":"SJ Szabo","year":"2000","unstructured":"Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH: A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell. 2000, 100 (6): 655-669. 10.1016\/S0092-8674(00)80702-3.","journal-title":"Cell"},{"issue":"7284","key":"1255_CR7","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1038\/nature08797","volume":"463","author":"T Vierbuchen","year":"2010","unstructured":"Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Sudhof TC, Wernig M: Direct conversion of fibroblasts to functional neurons by defined factors. Nature. 2010, 463 (7284): 1035-1041. 10.1038\/nature08797.","journal-title":"Nature"},{"issue":"12","key":"1255_CR8","doi-asserted-by":"publisher","first-page":"e1002300","DOI":"10.1371\/journal.pcbi.1002300","volume":"7","author":"R Chang","year":"2011","unstructured":"Chang R, Shoemaker R, Wang W: Systematic search for recipes to generate induced pluripotent stem cells. PLoS Comput Biol. 2011, 7 (12): e1002300-10.1371\/journal.pcbi.1002300.","journal-title":"PLoS Comput Biol"},{"key":"1255_CR9","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/1752-0509-5-50","volume":"5","author":"S Ding","year":"2011","unstructured":"Ding S, Wang W: Recipes and mechanisms of cellular reprogramming: a case study on budding yeast Saccharomyces cerevisiae. BMC Syst Biol. 2011, 5: 50-10.1186\/1752-0509-5-50.","journal-title":"BMC Syst Biol"},{"issue":"2","key":"1255_CR10","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1007\/BF02460618","volume":"57","author":"R Thomas","year":"1995","unstructured":"Thomas R, Thieffry D, Kaufman M: DYnamical behavior of biological regulatory networks.1. Biological role of feedback loops and practical use of the concept of the loop-characteristic state. Bull Math Biol. 1995, 57 (2): 247-276.","journal-title":"Bull Math Biol"},{"issue":"10","key":"1255_CR11","doi-asserted-by":"publisher","first-page":"2127","DOI":"10.1002\/stem.1473","volume":"31","author":"I Crespo","year":"2013","unstructured":"Crespo I, Del Sol A: A general strategy for cellular reprogramming: the importance of transcription factor cross-repression. Stem Cells. 2013, 31 (10): 2127-2135. 10.1002\/stem.1473.","journal-title":"Stem Cells"},{"issue":"Pt 11","key":"1255_CR12","doi-asserted-by":"publisher","first-page":"2553","DOI":"10.1242\/jcs.084822","volume":"125","author":"K Takahashi","year":"2012","unstructured":"Takahashi K: Cellular reprogramming\u2013lowering gravity on Waddington\u2019s epigenetic landscape. J Cell Sci. 2012, 125 (Pt 11): 2553-2560.","journal-title":"J Cell Sci"},{"key":"1255_CR13","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780195079517.001.0001","volume-title":"Origins of Order: self-organization and selection in evolution","author":"S Kauffman","year":"1993","unstructured":"Kauffman S: Origins of Order: self-organization and selection in evolution. 1993, New York: Oxford UniversityPress"},{"key":"1255_CR14","volume-title":"Macmillan Publishers Limited","author":"CH Waddington","year":"1957","unstructured":"Waddington CH: The Strategy of the Genes. Macmillan Publishers Limited. 1957, Allen & Unwin"},{"issue":"2","key":"1255_CR15","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.biosystems.2005.10.004","volume":"84","author":"L Mendoza","year":"2006","unstructured":"Mendoza L: A network model for the control of the differentiation process in Th cells. Biosystems. 2006, 84 (2): 101-114. 10.1016\/j.biosystems.2005.10.004.","journal-title":"Biosystems"},{"issue":"4","key":"1255_CR16","doi-asserted-by":"publisher","first-page":"e35440","DOI":"10.1371\/journal.pone.0035440","volume":"7","author":"M Moes","year":"2012","unstructured":"Moes M, Le Bechec A, Crespo I, Laurini C, Halavatyi A, Vetter G, Del Sol A, Friederich E: A novel network integrating a miRNA-203\/SNAI1 feedback loop which regulates epithelial to mesenchymal transitin. PLoS One. 2012, 7 (4): e35440-10.1371\/journal.pone.0035440.","journal-title":"PLoS One"},{"issue":"24","key":"1255_CR17","doi-asserted-by":"publisher","first-page":"4256","DOI":"10.4161\/cc.10.24.18552","volume":"10","author":"H Siemens","year":"2011","unstructured":"Siemens H, Jackstadt R, Hunten S, Kaller M, Menssen A, Gotz U, Hermeking H: miR-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions. Cell Cycle. 2011, 10 (24): 4256-4271. 10.4161\/cc.10.24.18552.","journal-title":"Cell Cycle"},{"issue":"5","key":"1255_CR18","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1093\/bioinformatics\/btg452","volume":"20","author":"N Daraselia","year":"2004","unstructured":"Daraselia N, Yuryev A, Egorov S, Novichkova S, Nikitin A, Mazo I: Extracting human protein interactions from MEDLINE using a full-sentence parser. Bioinformatics. 2004, 20 (5): 604-611. 10.1093\/bioinformatics\/btg452.","journal-title":"Bioinformatics"},{"issue":"13","key":"1255_CR19","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1093\/bioinformatics\/btg207","volume":"19","author":"S Novichkova","year":"2003","unstructured":"Novichkova S, Egorov S, Daraselia N: MedScan, a natural language processing engine for MEDLINE abstracts. Bioinformatics. 2003, 19 (13): 1699-1706. 10.1093\/bioinformatics\/btg207.","journal-title":"Bioinformatics"},{"issue":"suppl 1","key":"1255_CR20","doi-asserted-by":"publisher","first-page":"D119","DOI":"10.1093\/nar\/gkp803","volume":"38","author":"J Wang","year":"2010","unstructured":"Wang J, Lu M, Qiu C, Cui Q: TransmiR: a transcription factor\u2013microRNA regulation database. Nucleic Acids Res. 2010, 38 (suppl 1): D119-D122.","journal-title":"Nucleic Acids Res"},{"key":"1255_CR21","doi-asserted-by":"publisher","first-page":"D163","DOI":"10.1093\/nar\/gkq1107","volume":"39","author":"S-D Hsu","year":"2010","unstructured":"Hsu S-D, Lin F-M, Wu W-Y, Liang C, Huang W-C, Chan W-L, Tsai W-T, Chen G-Z, Lee C-J, Chiu C-M, et al: miRTarBase: a database curates experimentally validated microRNA\u2013target interactions. Nucleic Acids Res. 2010, 39: D163-D169.","journal-title":"Nucleic Acids Res"},{"key":"1255_CR22","doi-asserted-by":"publisher","first-page":"e8","DOI":"10.1093\/nar\/gks785","volume":"41","author":"I Crespo","year":"2012","unstructured":"Crespo I, Krishna A, Le Bechec A, Del Sol A: Predicting missing expression values in gene regulatory networks using a discrete logic modeling optimization guided by network stable states. Nucleic Acids Res. 2012, 41: e8-","journal-title":"Nucleic Acids Res"},{"issue":"5708","key":"1255_CR23","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1126\/science.1103336","volume":"307","author":"ES Hwang","year":"2005","unstructured":"Hwang ES, Szabo SJ, Schwartzberg PL, Glimcher LH: T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3. Science. 2005, 307 (5708): 430-433. 10.1126\/science.1103336.","journal-title":"Science"},{"issue":"1","key":"1255_CR24","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1084\/jem.192.1.105","volume":"192","author":"HJ Lee","year":"2000","unstructured":"Lee HJ, Takemoto N, Kurata H, Kamogawa Y, Miyatake S, O\u2019Garra A, Arai N: GATA-3 induces T helper cell type 2 (Th2) cytokine expression and chromatin remodeling in committed Th1 cells. J Exp Med. 2000, 192 (1): 105-115. 10.1084\/jem.192.1.105.","journal-title":"J Exp Med"},{"issue":"3","key":"1255_CR25","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1182\/blood.V54.3.713.713","volume":"54","author":"R Gallagher","year":"1979","unstructured":"Gallagher R, Collins S, Trujillo J, McCredie K, Ahearn M, Tsai S, Metzgar R, Aulakh G, Ting R, Ruscetti F, et al: Characterization of the continuous, differentiating myeloid cell line (HL-60) from a patient with acute promyelocytic leukemia. Blood. 1979, 54 (3): 713-733.","journal-title":"Blood"},{"issue":"1","key":"1255_CR26","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1182\/blood.V67.1.31.31","volume":"67","author":"M Tomonaga","year":"1986","unstructured":"Tomonaga M, Golde DW, Gasson JC: Biosynthetic (recombinant) human granulocyte-macrophage colony-stimulating factor: effect on normal bone marrow and leukemia cell lines. Blood. 1986, 67 (1): 31-36.","journal-title":"Blood"},{"issue":"5","key":"1255_CR27","doi-asserted-by":"publisher","first-page":"2458","DOI":"10.1073\/pnas.75.5.2458","volume":"75","author":"SJ Collins","year":"1978","unstructured":"Collins SJ, Ruscetti FW, Gallagher RE, Gallo RC: Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds. Proc Natl Acad Sci USA. 1978, 75 (5): 2458-2462. 10.1073\/pnas.75.5.2458.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"5","key":"1255_CR28","doi-asserted-by":"publisher","first-page":"2936","DOI":"10.1073\/pnas.77.5.2936","volume":"77","author":"TR Breitman","year":"1980","unstructured":"Breitman TR, Selonick SE, Collins SJ: Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. Proc Natl Acad Sci U S A. 1980, 77 (5): 2936-2940. 10.1073\/pnas.77.5.2936.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"1255_CR29","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/0145-2126(83)90057-7","volume":"7","author":"DM McCarthy","year":"1983","unstructured":"McCarthy DM, San Miguel JF, Freake HC, Green PM, Zola H, Catovsky D, Goldman JM: 1,25-dihydroxyvitamin D3 inhibits proliferation of human promyelocytic leukaemia (HL60) cells and induces monocyte-macrophage differentiation in HL60 and normal human bone marrow cells. Leuk Res. 1983, 7 (1): 51-55. 10.1016\/0145-2126(83)90057-7.","journal-title":"Leuk Res"},{"issue":"6","key":"1255_CR30","doi-asserted-by":"publisher","first-page":"2779","DOI":"10.1073\/pnas.76.6.2779","volume":"76","author":"G Rovera","year":"1979","unstructured":"Rovera G, Santoli D, Damsky C: Human promyelocytic leukemia cells in culture differentiate into macrophage-like cells when treated with a phorbol diester. Proc Natl Acad Sci USA. 1979, 76 (6): 2779-2783. 10.1073\/pnas.76.6.2779.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"12","key":"1255_CR31","doi-asserted-by":"publisher","first-page":"2372","DOI":"10.3109\/10428194.2011.603449","volume":"52","author":"M Shen","year":"2011","unstructured":"Shen M, Bunaciu RP, Congleton J, Jensen HA, Sayam LG, Varner JD, Yen A: Interferon regulatory factor-1 binds c-Cbl, enhances mitogen activated protein kinase signaling and promotes retinoic acid-induced differentiation of HL-60 human myelo-monoblastic leukemia cells. Leuk Lymphoma. 2011, 52 (12): 2372-2379. 10.3109\/10428194.2011.603449.","journal-title":"Leuk Lymphoma"},{"issue":"7356","key":"1255_CR32","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1038\/nature10263","volume":"475","author":"S Sekiya","year":"2011","unstructured":"Sekiya S, Suzuki A: Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors. Nature. 2011, 475 (7356): 390-393. 10.1038\/nature10263.","journal-title":"Nature"},{"issue":"1","key":"1255_CR33","first-page":"135","volume":"37","author":"MW McBurney","year":"1993","unstructured":"McBurney MW: P19 embryonal carcinoma cells. Int J Dev Biol. 1993, 37 (1): 135-140.","journal-title":"Int J Dev Biol"},{"issue":"3","key":"1255_CR34","first-page":"365","volume":"26","author":"DL Hu","year":"2010","unstructured":"Hu DL, Chen FK, Liu YQ, Sheng YH, Yang R, Kong XQ, Cao KJ, Gu HT, Qian LM: GATA-4 promotes the differentiation of P19 cells into cardiac myocytes. Int J Mol Med. 2010, 26 (3): 365-372.","journal-title":"Int J Mol Med"},{"issue":"9","key":"1255_CR35","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.3109\/14653249.2011.597380","volume":"13","author":"H Li","year":"2011","unstructured":"Li H, Zuo S, Pasha Z, Yu B, He Z, Wang Y, Yang X, Ashraf M, Xu M: GATA-4 promotes myocardial transdifferentiation of mesenchymal stromal cells via up-regulating IGFBP-4. Cytotherapy. 2011, 13 (9): 1057-1065. 10.3109\/14653249.2011.597380.","journal-title":"Cytotherapy"},{"issue":"7321","key":"1255_CR36","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/nature09531","volume":"468","author":"NY Chia","year":"2010","unstructured":"Chia NY, Chan YS, Feng B, Lu X, Orlov YL, Moreau D, Kumar P, Yang L, Jiang J, Lau MS, et al: A genome-wide RNAi screen reveals determinants of human embryonic stem cell identity. Nature. 2010, 468 (7321): 316-320. 10.1038\/nature09531.","journal-title":"Nature"},{"issue":"4","key":"1255_CR37","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1177\/1947601911410224","volume":"2","author":"BT Spike","year":"2011","unstructured":"Spike BT, Wahl GM: p53, Stem cells, and reprogramming: tumor suppression beyond guarding the genome. Genes Cancer. 2011, 2 (4): 404-419. 10.1177\/1947601911410224.","journal-title":"Genes Cancer"},{"issue":"8","key":"1255_CR38","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1038\/nbt.1554","volume":"27","author":"K Miura","year":"2009","unstructured":"Miura K, Okada Y, Aoi T, Okada A, Takahashi K, Okita K, Nakagawa M, Koyanagi M, Tanabe K, Ohnuki M, et al: Variation in the safety of induced pluripotent stem cell lines. Nat Biotechnol. 2009, 27 (8): 743-745. 10.1038\/nbt.1554.","journal-title":"Nat Biotechnol"},{"issue":"7279","key":"1255_CR39","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1038\/nature08712","volume":"463","author":"MS Carro","year":"2010","unstructured":"Carro MS, Lim WK, Alvarez MJ, Bollo RJ, Zhao X, Snyder EY, Sulman EP, Anne SL, Doetsch F, Colman H, et al: The transcriptional network for mesenchymal transformation of brain tumours. Nature. 2010, 463 (7279): 318-325. 10.1038\/nature08712.","journal-title":"Nature"},{"issue":"Suppl 1","key":"1255_CR40","doi-asserted-by":"publisher","first-page":"S7","DOI":"10.1186\/1471-2105-7-S1-S7","volume":"7","author":"AA Margolin","year":"2006","unstructured":"Margolin AA, Nemenman I, Basso K, Wiggins C, Stolovitzky G, Dalla Favera R, Califano A: ARACNE: an algorithm for the reconstruction of gene regulatory networks in a mammalian cellular context. BMC Bioinformatics. 2006, 7 (Suppl 1): S7-10.1186\/1471-2105-7-S1-S7.","journal-title":"BMC Bioinformatics"},{"issue":"7193","key":"1255_CR41","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1038\/453301a","volume":"453","author":"N DeWitt","year":"2008","unstructured":"DeWitt N: Regenerative medicine. Nature. 2008, 453 (7193): 301-10.1038\/453301a.","journal-title":"Nature"},{"issue":"6","key":"1255_CR42","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1016\/j.cell.2012.02.031","volume":"148","author":"AB Cherry","year":"2012","unstructured":"Cherry AB, Daley GQ: Reprogramming cellular identity for regenerative medicine. Cell. 2012, 148 (6): 1110-1122. 10.1016\/j.cell.2012.02.031.","journal-title":"Cell"},{"issue":"16","key":"1255_CR43","doi-asserted-by":"publisher","first-page":"2263","DOI":"10.1093\/bioinformatics\/btr373","volume":"27","author":"T Schaffter","year":"2011","unstructured":"Schaffter T, Marbach D, Floreano D: GeneNetWeaver: in silico benchmark generation and performance profiling of network inference methods. Bioinformatics. 2011, 27 (16): 2263-2270. 10.1093\/bioinformatics\/btr373.","journal-title":"Bioinformatics"},{"issue":"1\u20132","key":"1255_CR44","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.gene.2008.04.015","volume":"419","author":"F Mollinedo","year":"2008","unstructured":"Mollinedo F, Lopez-Perez R, Gajate C: Differential gene expression patterns coupled to commitment and acquisition of phenotypic hallmarks during neutrophil differentiation of human leukaemia HL-60 cells. Gene. 2008, 419 (1\u20132): 16-26.","journal-title":"Gene"},{"issue":"14","key":"1255_CR45","doi-asserted-by":"publisher","first-page":"4943","DOI":"10.1073\/pnas.0408125102","volume":"102","author":"T Koide","year":"2005","unstructured":"Koide T, Hayata T, Cho KW: Xenopus as a model system to study transcriptional regulatory networks. Proc Natl Acad Sci USA. 2005, 102 (14): 4943-4948. 10.1073\/pnas.0408125102.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1255_CR46","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/msb4100102","volume":"2","author":"JC Locke","year":"2006","unstructured":"Locke JC, Kozma-Bognar L, Gould PD, Feher B, Kevei E, Nagy F, Turner MS, Hall A, Millar AJ: Experimental validation of a predicted feedback loop in the multi-oscillator clock of Arabidopsis thaliana. Mol Syst Biol. 2006, 2: 59-","journal-title":"Mol Syst Biol"},{"issue":"5","key":"1255_CR47","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1016\/S0022-2836(02)00994-4","volume":"323","author":"N Rosenfeld","year":"2002","unstructured":"Rosenfeld N, Elowitz MB, Alon U: Negative autoregulation speeds the response times of transcription networks. J Mol Biol. 2002, 323 (5): 785-793. 10.1016\/S0022-2836(02)00994-4.","journal-title":"J Mol Biol"},{"issue":"17","key":"1255_CR48","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1093\/bioinformatics\/btn336","volume":"24","author":"A Garg","year":"2008","unstructured":"Garg A, Di Cara A, Xenarios I, Mendoza L, De Micheli G: Synchronous versus asynchronous modeling of gene regulatory networks. Bioinformatics. 2008, 24 (17): 1917-1925. 10.1093\/bioinformatics\/btn336.","journal-title":"Bioinformatics"},{"key":"1255_CR49","first-page":"62","volume-title":"Lecture Notes in Computer Science, Vol 4453","author":"A Garg","year":"2007","unstructured":"Garg A, Xenarios I, Mendoza L, DeMicheli G: An efficient method for dynamic analysis of gene regulatory networks and in silico gene perturbation experiments. Lecture Notes in Computer Science, Vol 4453. Edited by: Speed T, Huang H. 2007, Berling\/Heidelberg: Springer, 62-76."},{"issue":"1","key":"1255_CR50","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1049\/sb:20045011","volume":"1","author":"H Conzelmann","year":"2004","unstructured":"Conzelmann H, Saez-Rodriguez J, Sauter T, Bullinger E, Allgower F, Gilles ED: Reduction of mathematical models of signal transduction networks: simulation-based approach applied to EGF receptor signalling. Syst Biol (Stevenage). 2004, 1 (1): 159-169. 10.1049\/sb:20045011.","journal-title":"Syst Biol (Stevenage)"},{"issue":"1","key":"1255_CR51","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1137\/0204007","volume":"4","author":"DB Johnson","year":"1975","unstructured":"Johnson DB: Finding all the elementary circuits of a directed graph. SIAM J Comput. 1975, 4 (1): 77-84. 10.1137\/0204007.","journal-title":"SIAM J Comput"}],"container-title":["BMC Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-7-140.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T22:05:41Z","timestamp":1716329141000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcsystbiol.biomedcentral.com\/articles\/10.1186\/1752-0509-7-140"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["1255"],"URL":"https:\/\/doi.org\/10.1186\/1752-0509-7-140","relation":{},"ISSN":["1752-0509"],"issn-type":[{"value":"1752-0509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12]]},"assertion":[{"value":"31 May 2013","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 December 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"140"}}