{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T12:58:22Z","timestamp":1774789102833,"version":"3.50.1"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"S19","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2016,12]]},"DOI":"10.1186\/s12859-016-1363-4","type":"journal-article","created":{"date-parts":[[2016,12,22]],"date-time":"2016-12-22T12:44:50Z","timestamp":1482410690000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Statistical ensemble of gene regulatory networks of macrophage differentiation"],"prefix":"10.1186","volume":"17","author":[{"given":"Filippo","family":"Castiglione","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Tieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Palma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdul Salam","family":"Jarrah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,12,22]]},"reference":[{"key":"1363_CR1","first-page":"bbv012","volume":"2015","author":"A Cappuccio","year":"2015","unstructured":"Cappuccio A, Tieri P, Castiglione F. Multiscale modelling in immunology: a review. Brief Bioinform. 2015; 2015:bbv012.","journal-title":"Brief Bioinform"},{"key":"1363_CR2","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1511\/2007.64.134","volume":"95","author":"S Schnell","year":"2007","unstructured":"Schnell S, Grima R, Maini P. Multiscale Modeling in Biology. Am Sci. 2007; 95:134.","journal-title":"Am Sci"},{"issue":"1-3","key":"1363_CR3","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.pbiomolbio.2007.07.019","volume":"96","author":"J Southern","year":"2008","unstructured":"Southern J, Pitt-Francis J, Whiteley J, et al.Multi-scale computational modelling in biology and physiology. Prog Biophys Mol Biol. 2008; 96(1-3):60\u201389.","journal-title":"Prog Biophys Mol Biol"},{"key":"1363_CR4","doi-asserted-by":"crossref","DOI":"10.1201\/9781134111589","volume-title":"Physical Biology of the Cell","author":"R Phillips","year":"2012","unstructured":"Phillips R, Kondev J, Theriot J, Garcia H. Physical Biology of the Cell. New York: Garland Science; 2012."},{"issue":"5","key":"1363_CR5","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1093\/bib\/bbt021","volume":"15","author":"M Secrier","year":"2014","unstructured":"Secrier M, Schneider R. Visualizing time-related data in biology: a review. Brief Bioinform. 2014; 15(5):771\u201382.","journal-title":"Brief Bioinform"},{"issue":"3","key":"1363_CR6","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/gm538","volume":"6","author":"O Wolkenhauer","year":"2014","unstructured":"Wolkenhauer O, Auffray C, Brass O, et al.Enabling multiscale modeling in systems medicine. Genome Med. 2014; 6(3):21.","journal-title":"Genome Med"},{"key":"1363_CR7","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1109\/RBME.2009.2036204","volume":"2","author":"PJ Hunter","year":"2009","unstructured":"Hunter PJ, Viceconti M. The VPH-Physiome project: stand- ards and tools for multiscale modeling in clinical applications. IEEE Rev Biomed Eng. 2009; 2:40\u201353.","journal-title":"IEEE Rev Biomed Eng"},{"issue":"7446","key":"1363_CR8","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nature12034","volume":"496","author":"TA Wynn","year":"2013","unstructured":"Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature. 2013; 496(7446):445\u201355.","journal-title":"Nature"},{"key":"1363_CR9","volume-title":"Advances in Bioinformatics and Computational Biology, Lecture Notes in Computer Science, Vol. 8826","author":"P Tieri","year":"2014","unstructured":"Tieri P, Prana V, Colombo T, Santoni D, Castiglione F. Multi-scale simulation of T helper lymphocyte differentiation In: Campos S, editor. Advances in Bioinformatics and Computational Biology, Lecture Notes in Computer Science, Vol. 8826. Belo Horizonte: Springer Verlag: 2014. p. 123\u201334. ISBN 978-3-319-12417-9, http:\/\/www.springer.com\/it\/book\/9783319124179?wt_mc=ThirdParty.SpringerLink.3.EPR653.About_eBook ."},{"issue":"1920","key":"1363_CR10","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1098\/rsta.2010.0067","volume":"368","author":"M Halling-Brown","year":"2010","unstructured":"Halling-Brown M, Pappalardo F, Rapin N, et al.ImmunoGrid: towards agent-based simulations of the human immune system at a natural scale. Philosophical Trans Roy Soc a-Math Phys Eng Sci. 2010; 368(1920):2799\u2013815.","journal-title":"Philosophical Trans Roy Soc a-Math Phys Eng Sci"},{"issue":"5","key":"1363_CR11","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.immuni.2010.05.007","volume":"32","author":"S Gordon","year":"2010","unstructured":"Gordon S, Martinez FO. Alternative Activation of Macrophages: Mechanism and Functions. Immunity. 2010; 32(5):593\u2013604.","journal-title":"Immunity"},{"issue":"5966","key":"1363_CR12","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1126\/science.1178331","volume":"327","author":"F Geissmann","year":"2010","unstructured":"Geissmann F, et al.Development of monocytes, macrophages, and dendritic cells. Science. 2010; 327(5966):656\u201361.","journal-title":"Science"},{"issue":"12","key":"1363_CR13","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1038\/nri1733","volume":"5","author":"S Gordon","year":"2005","unstructured":"Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol. 2005; 5(12):953\u201364.","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"1363_CR14","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/imr.12223","volume":"262","author":"S Gordon","year":"2014","unstructured":"Gordon S, Pluddemann A, Estrada FM. Macrophage heterogeneity in tissues: phenotypic diversity and functions. Immunol Rev. 2014; 262(1):36\u201355.","journal-title":"Immunol Rev"},{"issue":"11","key":"1363_CR15","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S1471-4906(02)02302-5","volume":"23","author":"A Mantovani","year":"2002","unstructured":"Mantovani A, Sozzani S, Locati M, Allavena P, Sica A. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002; 23(11):549\u201355.","journal-title":"Trends Immunol"},{"issue":"14-15","key":"1363_CR16","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1016\/j.micinf.2007.09.002","volume":"9","author":"DM Bowdish","year":"2007","unstructured":"Bowdish DM, Loffredo MS, Mukhopadhyay S, Mantovani A, Gordon S. Macrophage receptors implicated in the adaptive form of innate immunity. Microbes Infect. 2007; 9(14-15):1680\u20137.","journal-title":"Microbes Infect"},{"issue":"12","key":"1363_CR17","doi-asserted-by":"crossref","first-page":"3269","DOI":"10.1002\/eji.200838918","volume":"38","author":"A Mantovani","year":"2008","unstructured":"Mantovani A. From phagocyte diversity and activation to probiotics: back to Metchnikoff. Eur J Immunol. 2008; 38(12):3269\u201373.","journal-title":"Eur J Immunol"},{"issue":"10","key":"1363_CR18","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/ni.1937","volume":"11","author":"A Mantovani","year":"2010","unstructured":"Biswas, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010; 11(10):889\u201396.","journal-title":"Nat Immunol"},{"issue":"11-12","key":"1363_CR19","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1002\/bies.20834","volume":"30","author":"HA Kestler","year":"2008","unstructured":"Kestler HA, Wawra C, Kracher B, K\u00fchl M. Network modeling of signal transduction: establishing the global view. Bioessays. 2008; 30(11-12):1110\u201325.","journal-title":"Bioessays"},{"key":"1363_CR20","first-page":"2","volume":"6","author":"Y Sang","year":"2015","unstructured":"Sang Y, Miller LC, Blecha F. Macrophage Polarization in Virus-Host Interactions. J Clin Cell Immunol. 2015; 6:2.","journal-title":"J Clin Cell Immunol"},{"issue":"5164","key":"1363_CR21","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1126\/science.8197455","volume":"264","author":"JE Jr Darnell","year":"1994","unstructured":"Darnell JE Jr, Kerr IM, Stark GR. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994; 264(5164):1415\u201321.","journal-title":"Science"},{"issue":"5","key":"1363_CR22","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/nri1604","volume":"5","author":"LC Platanias","year":"2005","unstructured":"Platanias LC. Mechanism of type I and type II interferon mediated signaling. Nat Rev Immunol. 2005; 5(5):375\u201386.","journal-title":"Nat Rev Immunol"},{"issue":"11","key":"1363_CR23","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1038\/nri3088","volume":"11","author":"T Lawrence","year":"2011","unstructured":"Lawrence T, Natoli G. Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat Rev Immunol. 2011; 11(11):750\u201361.","journal-title":"Nat Rev Immunol"},{"key":"1363_CR24","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/978-1-59745-396-7_15","volume":"531","author":"F Brombacher","year":"2009","unstructured":"Brombacher F, Arendse B, Peterson R, Holscher A, Holscher C. Analyzing classical and alternative macrophage activation in macrophage\/neutrophil-specific IL-4 receptor-alpha-deficient mice. Methods Mol Biol. 2009; 531:225\u201352.","journal-title":"Methods Mol Biol"},{"key":"1363_CR25","first-page":"1","volume":"2","author":"I Rauch","year":"2013","unstructured":"Rauch I, Ml\u0308ler M, Decker T. The regulation of inflammation by interferons and their STATs. JAKSTAT. 2013; 2:1.","journal-title":"JAKSTAT"},{"issue":"5","key":"1363_CR26","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ni.1863","volume":"11","author":"T Kawai","year":"2010","unstructured":"Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010; 11(5):373\u201384.","journal-title":"Nat Immunol"},{"issue":"4","key":"1363_CR27","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1189\/jlb.2A0414-191R","volume":"96","author":"F Sheikh","year":"2014","unstructured":"Sheikh F, Dickensheets H, Gamero AM, Vogel SN, Donnelly RP. An essential role for IFN-? in the induction of IFN-stimulated gene expression by LPS in macrophages. J Leukoc Biol. 2014; 96(4):591\u2013600.","journal-title":"J Leukoc Biol"},{"issue":"10","key":"1363_CR28","doi-asserted-by":"crossref","first-page":"5887","DOI":"10.4049\/jimmunol.167.10.5887","volume":"167","author":"T Kawai","year":"2001","unstructured":"Kawai T, Takeuchi O, Fujita T, Inoue J, Mh\u0308lradt PF, Sato S, Hoshino K, Akira S. Lipopolysaccharide stimulates the MyD88- independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes. J Immunol. 2001; 167(10):5887\u201394.","journal-title":"J Immunol"},{"issue":"3","key":"1363_CR29","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S1074-7613(02)00390-4","volume":"17","author":"S Doyle","year":"2002","unstructured":"Doyle S, Vaidya S, O\u2019Connell R, Dadgostar H, Dempsey P, Wu T, Rao G, Sun R, Haberland M, Modlin R, Cheng G. IRF3 mediates a TLR3\/TLR4-specific antiviral gene program. Immunity. 2002; 17(3):251\u201363.","journal-title":"Immunity"},{"key":"1363_CR30","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1242\/jcs.01166","volume":"117","author":"CJ Lowenstein","year":"2004","unstructured":"Lowenstein CJ, Padalko E. iNOS (NOS2) at a glance - Poster. J Cell Sci. 2004; 117:2865\u20137.","journal-title":"J Cell Sci"},{"issue":"1","key":"1363_CR31","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nri978","volume":"3","author":"S Gordon","year":"2003","unstructured":"Gordon S. Alternative activation of macrophages. Nat Rev Immunol. 2003; 3(1):23\u201335.","journal-title":"Nat Rev Immunol"},{"key":"1363_CR32","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1146\/annurev.immunol.19.1.683","volume":"19","author":"KW Moore","year":"2001","unstructured":"Moore KW, de Waal Malefyt R, Coffman RL, O\u2019Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001; 19:683\u2013765.","journal-title":"Annu Rev Immunol"},{"key":"1363_CR33","doi-asserted-by":"crossref","unstructured":"Foey AD. Macrophages Masters of immune activation, suppression and deviation. Immune Response Activation. 2014:121\u201349. http:\/\/www.intechopen.com\/books\/immune-responseactivation\/macrophages-masters-of-immune-activation-suppression-and-deviation .","DOI":"10.5772\/57541"},{"issue":"6662","key":"1363_CR34","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/34178","volume":"391","author":"M Ricote","year":"1998","unstructured":"Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK. The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature. 1998; 391(6662):79\u201382.","journal-title":"Nature"},{"issue":"7059","key":"1363_CR35","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nature03988","volume":"437","author":"G Pascual","year":"2005","unstructured":"Pascual G, et al.A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR- \u03b3. Nature. 2005; 437(7059):759\u201363.","journal-title":"Nature"},{"issue":"7","key":"1363_CR36","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.1172\/JCI45444","volume":"121","author":"X Liao","year":"2011","unstructured":"Liao X, et al.Kr\u00fcppel-like factor 4 regulates macrophage polarization. Journal Clin Investig. 2011; 121(7):2736\u201349.","journal-title":"Journal Clin Investig"},{"issue":"12","key":"1363_CR37","doi-asserted-by":"crossref","first-page":"6011","DOI":"10.4049\/jimmunol.1402797","volume":"194","author":"N Kapoor","year":"2015","unstructured":"Kapoor N, et al.Transcription factors STAT6 and KLF4 implement macrophage polarization via the dual catalytic powers of MCPIP. J Immunol. 2015; 194(12):6011\u201323.","journal-title":"J Immunol"},{"key":"1363_CR38","doi-asserted-by":"crossref","first-page":"357","DOI":"10.3389\/fimmu.2014.00357","volume":"5","author":"HM Wilson","year":"2014","unstructured":"Wilson HM. SOCS proteins in macrophage polarization and function. Front Immunol. 2014; 5:357.","journal-title":"Front Immunol"},{"key":"1363_CR39","volume-title":"Elementary Principles in Statistical Mechanics","author":"JW Gibbs","year":"1902","unstructured":"Gibbs JW. Elementary Principles in Statistical Mechanics. New York: Charles Scribner\u2019s Sons; 1902."},{"key":"1363_CR40","unstructured":"Murphy, Kenneth. Janeway\u2019s Immunobiology. Garland Science. 2011. http:\/\/www.garlandscience.com\/product\/isbn\/9780815342434 ."},{"key":"1363_CR41","volume-title":"Human Biology and Health","author":"D Maton","year":"1997","unstructured":"Maton D, Hopkins J, McLaughlin ChW, Johnson S, Warner MQ, LaHart D, Wright JD, Kulkarni DV. Human Biology and Health. Englewood: Prentice Hall; 1997."},{"issue":"6","key":"1363_CR42","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1189\/jlb.0406249","volume":"80","author":"JP Edwards","year":"2006","unstructured":"Edwards JP, Zhang X, Frauwirth KA, Mosser DM. Biochemical and functional characterization of three activated macrophage populations. J Leukoc Biol. 2006; 80(6):1298\u2013307.","journal-title":"J Leukoc Biol"},{"issue":"12","key":"1363_CR43","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/nri2448","volume":"8","author":"DM Mosser","year":"2008","unstructured":"Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008; 8(12):958\u201369.","journal-title":"Nat Rev Immunol"},{"issue":"6","key":"1363_CR44","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1093\/bfgp\/elt028","volume":"12","author":"AP Hutchins","year":"2013","unstructured":"Hutchins AP, Diez D, Miranda-Saavedra D. The IL-10\/STAT3-mediated anti-inflammatory response: recent developments and future challenges. Brief Funct Genom. 2013; 12(6):489\u201398.","journal-title":"Brief Funct Genom"},{"issue":"3","key":"1363_CR45","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.4049\/jimmunol.1500146","volume":"195","author":"DE Sanin","year":"2015","unstructured":"Sanin DE, Prendergast CT, Mountford AP. IL-10 Production in Macrophages Is Regulated by a TLR-Driven CREB-Mediated Mechanism That Is Linked to Genes Involved in Cell Metabolism. J Immunol. 2015; 195(3):1218\u201332.","journal-title":"J Immunol"},{"key":"1363_CR46","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s12016-015-8487-6","volume":"13","author":"M Frieri","year":"2015","unstructured":"Frieri M. Mast Cell Activation Syndrome. Clin Rev Allergy Immunol. 2015; 13:27. doi: 10.1007\/s12016-015-8487-6 .","journal-title":"Clin Rev Allergy Immunol"},{"key":"1363_CR47","doi-asserted-by":"publisher","unstructured":"Jou IM, Lin CF, Tsai KJ, Wei SJ. Macrophage-Mediated Inflammatory Disorders. Mediat Inflamm. 2013. doi: 10.1155\/2013\/316482 .","DOI":"10.1155\/2013\/316482"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-016-1363-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T21:07:22Z","timestamp":1568668042000},"score":1,"resource":{"primary":{"URL":"http:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-016-1363-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12]]},"references-count":47,"journal-issue":{"issue":"S19","published-print":{"date-parts":[[2016,12]]}},"alternative-id":["1363"],"URL":"https:\/\/doi.org\/10.1186\/s12859-016-1363-4","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12]]},"article-number":"506"}}