{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T18:32:38Z","timestamp":1776018758072,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1005608","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,7,7]],"date-time":"2017-07-07T00:00:00Z","timestamp":1499385600000}}],"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2017,6,22]],"date-time":"2017-06-22T00:00:00Z","timestamp":1498089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2015-03807"],"award-info":[{"award-number":["2015-03807"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2015-03807"],"award-info":[{"award-number":["2015-03807"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1005608","type":"journal-article","created":{"date-parts":[[2017,6,22]],"date-time":"2017-06-22T13:27:31Z","timestamp":1498138051000},"page":"e1005608","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["LASSIM\u2014A network inference toolbox for genome-wide mechanistic modeling"],"prefix":"10.1371","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9395-6025","authenticated-orcid":true,"given":"Rasmus","family":"Magnusson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido Pio","family":"Mariotti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4031-4093","authenticated-orcid":true,"given":"Mattias","family":"K\u00f6ps\u00e9n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"L\u00f6vfors","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danuta R.","family":"Gawel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecka","family":"J\u00f6rnsten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rg","family":"Linde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4867-6707","authenticated-orcid":true,"given":"Torbj\u00f6rn E. M.","family":"Nordling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4261-0291","authenticated-orcid":true,"given":"Elin","family":"Nyman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvie","family":"Schulze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colm E.","family":"Nestor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunnar","family":"Cedersund","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikael","family":"Benson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0064-1791","authenticated-orcid":true,"given":"Andreas","family":"Tj\u00e4rnberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0048-4063","authenticated-orcid":true,"given":"Mika","family":"Gustafsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2017,6,22]]},"reference":[{"issue":"5560","key":"ref1","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1126\/science.1069492","article-title":"Systems biology: a brief overview","volume":"295","author":"H. Kitano","year":"2002","journal-title":"Science"},{"issue":"7","key":"ref2","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/nbt0702-649","article-title":"In silico biology through &quot;omics&quot;","volume":"20","author":"B. Palsson","year":"2002","journal-title":"Nat Biotechnol"},{"issue":"7","key":"ref3","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1039\/c3mb25489e","article-title":"Bridging the layers: towards integration of signal transduction, regulation and metabolism into mathematical models","volume":"9","author":"E. Gon\u00e7alves","year":"2013","journal-title":"Mol Biosyst"},{"key":"ref4","article-title":"Data- and knowledge-based modeling of gene regulatory networks: An update","author":"J. Linde","year":"2015","journal-title":"EXCLI Journal"},{"issue":"1","key":"ref5","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1089\/10665270252833208","article-title":"Modeling and simulation of genetic regulatory systems: a literature review","volume":"9","author":"H. de Jong","year":"2002","journal-title":"J Comput Biol"},{"issue":"3","key":"ref6","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1109\/TCBB.2005.35","article-title":"Constructing and analyzing a large-scale gene-to-gene regulatory network\u2014lasso-constrained inference and biological validation","volume":"2","author":"M. Gustafsson","year":"2005","journal-title":"IEEE\/ACM Trans Comput Biol Bioinform"},{"issue":"4","key":"ref7","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1049\/iet-syb.2008.0112","article-title":"Genome-wide system analysis reveals stable yet flexible network dynamics in yeast","volume":"3","author":"M. Gustafsson","year":"2009","journal-title":"IET Syst Biol"},{"issue":"14","key":"ref8","doi-asserted-by":"crossref","first-page":"6286","DOI":"10.1073\/pnas.0913357107","article-title":"Revealing strengths and weaknesses of methods for gene network inference","volume":"107","author":"D. Marbach","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1196\/annals.1407.021","article-title":"Dialogue on reverse-engineering assessment and methods: the DREAM of high-throughput pathway inference","volume":"1115","author":"G. Stolovitzky","year":"2007","journal-title":"Ann N Y Acad Sci"},{"issue":"1","key":"ref10","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1039\/C4MB00419A","article-title":"Avoiding pitfalls in L-1-regularised inference of gene networks","volume":"11","author":"A. Tjarnberg","year":"2015","journal-title":"Molecular Biosystems"},{"issue":"12","key":"ref11","doi-asserted-by":"crossref","first-page":"e29165","DOI":"10.1371\/journal.pone.0029165","article-title":"Gene regulatory network reconstruction using Bayesian networks, the Dantzig Selector, the Lasso and their meta-analysis","volume":"6","author":"M. Vignes","year":"2011","journal-title":"PLoS One"},{"issue":"12","key":"ref12","doi-asserted-by":"crossref","first-page":"e14147","DOI":"10.1371\/journal.pone.0014147","article-title":"Gene regulatory networks from multifactorial perturbations using Graphical Lasso: application to the DREAM4 challenge","volume":"5","author":"P. Men\u00e9ndez","year":"2010","journal-title":"PLoS One"},{"issue":"5","key":"ref13","doi-asserted-by":"crossref","first-page":"R36","DOI":"10.1186\/gb-2006-7-5-r36","article-title":"The Inferelator: an algorithm for learning parsimonious regulatory networks from systems-biology data sets de novo","volume":"7","author":"R. Bonneau","year":"2006","journal-title":"Genome Biol"},{"issue":"Suppl 1","key":"ref14","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1186\/1471-2105-7-S1-S7","article-title":"ARACNE: an algorithm for the reconstruction of gene regulatory networks in a mammalian cellular context","volume":"7","author":"A.A. Margolin","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"e118","DOI":"10.1038\/psp.2014.16","article-title":"Effects of IL-1\u03b2-Blocking Therapies in Type 2 Diabetes Mellitus: A Quantitative Systems Pharmacology Modeling Approach to Explore Underlying Mechanisms","volume":"3","author":"R. Palm\u00e9r","year":"2014","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"issue":"4","key":"ref16","doi-asserted-by":"crossref","first-page":"e95700","DOI":"10.1371\/journal.pone.0095700","article-title":"Physiologically realistic and validated mathematical liver model revels hepatobiliary transfer rates for Gd-EOB-DTPA using human DCE-MRI data","volume":"9","author":"M.F. Forsgren","year":"2014","journal-title":"PLoS One"},{"issue":"14","key":"ref17","doi-asserted-by":"crossref","first-page":"9867","DOI":"10.1074\/jbc.M112.432062","article-title":"Insulin signaling in type 2 diabetes: experimental and modeling analyses reveal mechanisms of insulin resistance in human adipocytes","volume":"288","author":"C. Br\u00e4nnmark","year":"2013","journal-title":"J Biol Chem"},{"issue":"6","key":"ref18","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1111\/j.1742-4658.2012.08488.x","article-title":"Mechanistic explanations for counter-intuitive phosphorylation dynamics of the insulin receptor and insulin receptor substrate-1 in response to insulin in murine adipocytes","volume":"279","author":"E. Nyman","year":"2012","journal-title":"FEBS J"},{"issue":"5984","key":"ref19","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1126\/science.1184913","article-title":"Covering a broad dynamic range: information processing at the erythropoietin receptor","volume":"328","author":"V. Becker","year":"2010","journal-title":"Science"},{"issue":"3","key":"ref20","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1073\/pnas.0237333100","article-title":"Identification of nucleocytoplasmic cycling as a remote sensor in cellular signaling by databased modeling","volume":"100","author":"I. Swameye","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"ref21","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1111\/j.1742-4658.2008.06845.x","article-title":"Systems biology: model based evaluation and comparison of potential explanations for given biological data","volume":"276","author":"G. Cedersund","year":"2009","journal-title":"FEBS J"},{"key":"ref22","article-title":"Crosstalks via mTORC2 can explain enhanced activation in response to insulin in diabetic patients","author":"R. Magnusson","year":"2016","journal-title":"Biosci Rep"},{"key":"ref23","first-page":"257","article-title":"Encyclopedia of Machine Learning","author":"E. Keogh","year":"2010"},{"issue":"8","key":"ref24","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1039\/b702142a","article-title":"Deduction of intracellular sub-systems from a topological description of the network","volume":"3","author":"T.E. Nordling","year":"2007","journal-title":"Mol Biosyst"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/j.1749-6632.2008.03764.x","article-title":"Reverse engineering of gene networks with LASSO and nonlinear basis functions","volume":"1158","author":"M. Gustafsson","year":"2009","journal-title":"Ann N Y Acad Sci"},{"issue":"11","key":"ref26","doi-asserted-by":"crossref","first-page":"e1222","DOI":"10.1371\/journal.pone.0001222","article-title":"A network analysis of the human T-cell activation gene network identifies JAGGED1 as a therapeutic target for autoimmune diseases","volume":"2","author":"R. Palacios","year":"2007","journal-title":"PLoS One"},{"issue":"12","key":"ref27","doi-asserted-by":"crossref","first-page":"e1001032","DOI":"10.1371\/journal.pcbi.1001032","article-title":"Combining network modeling and gene expression microarray analysis to explore the dynamics of Th1 and Th2 cell regulation","volume":"6","author":"M. Pedicini","year":"2010","journal-title":"PLoS Comput Biol"},{"issue":"1","key":"ref28","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1600-065X.2010.00951.x","article-title":"Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors","volume":"238","author":"J. Zhu","year":"2010","journal-title":"Immunol Rev"},{"issue":"4","key":"ref29","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/nri2958","article-title":"Genomic views of STAT function in CD4+ T helper cell differentiation","volume":"11","author":"J.J. O'Shea","year":"2011","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"ref30","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/imr.12032","article-title":"Early signaling events that underlie fate decisions of naive CD4(+) T cells toward distinct T-helper cell subsets","volume":"252","author":"H. Yamane","year":"2013","journal-title":"Immunol Rev"},{"key":"ref31","first-page":"125","article-title":"Transcriptional regulatory networks for CD4 T cell differentiation","volume":"381","author":"D. Christie","year":"2014","journal-title":"Curr Top Microbiol Immunol"},{"key":"ref32","first-page":"151","article-title":"Parallel Architectures and Bioinspired Algorithms","author":"D. Izzo","year":"2012"},{"issue":"1","key":"ref33","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1093\/nar\/gkl1001","article-title":"Nonlinear differential equation model for quantification of transcriptional regulation applied to microarray data of Saccharomyces cerevisiae","volume":"35","author":"T.T. Vu","year":"2007","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"ref34","doi-asserted-by":"crossref","first-page":"e8121","DOI":"10.1371\/journal.pone.0008121","article-title":"Improved reconstruction of in silico gene regulatory networks by integrating knockout and perturbation data","volume":"5","author":"K.Y. Yip","year":"2010","journal-title":"PLoS One"},{"issue":"313","key":"ref35","doi-asserted-by":"crossref","first-page":"313ra178","DOI":"10.1126\/scitranslmed.aad2722","article-title":"A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases","volume":"7","author":"M. Gustafsson","year":"2015","journal-title":"Sci Transl Med"},{"issue":"1","key":"ref36","doi-asserted-by":"crossref","first-page":"e1004059","DOI":"10.1371\/journal.pgen.1004059","article-title":"DNA methylation changes separate allergic patients from healthy controls and may reflect altered CD4+ T-cell population structure","volume":"10","author":"C.E. Nestor","year":"2014","journal-title":"PLoS Genet"},{"issue":"4","key":"ref37","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/nmeth.3772","article-title":"Analysis of computational footprinting methods for DNase sequencing experiments","volume":"13","author":"E.G. Gusmao","year":"2016","journal-title":"Nat Meth"},{"issue":"7414","key":"ref38","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature11247","article-title":"An integrated encyclopedia of DNA elements in the human genome","volume":"489","year":"2012","journal-title":"Nature"},{"issue":"D1","key":"ref39","doi-asserted-by":"crossref","first-page":"D116","DOI":"10.1093\/nar\/gkv1249","article-title":"HOCOMOCO: expansion and enhancement of the collection of transcription factor binding sites models","volume":"44","author":"I.V. Kulakovskiy","year":"2016","journal-title":"Nucleic Acids Res"},{"issue":"Database issue","key":"ref40","doi-asserted-by":"crossref","first-page":"D117","DOI":"10.1093\/nar\/gku1045","article-title":"UniPROBE, update 2015: new tools and content for the online database of protein-binding microarray data on protein-DNA interactions","volume":"43","author":"M.A. Hume","year":"2015","journal-title":"Nucleic Acids Res"},{"issue":"D1","key":"ref41","doi-asserted-by":"crossref","first-page":"D110","DOI":"10.1093\/nar\/gkv1176","article-title":"JASPAR 2016: a major expansion and update of the open-access database of transcription factor binding profiles","volume":"44","author":"A. Mathelier","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1038\/ncomms2260","article-title":"T-bet and GATA3 orchestrate Th1 and Th2 differentiation through lineage-specific targeting of distal regulatory elements","volume":"3","author":"A. Kanhere","year":"2012","journal-title":"Nat Commun"},{"issue":"1","key":"ref43","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/j.1398-9995.2011.02707.x","article-title":"Increased expression of IRF4 and ETS1 in CD4+ cells from patients with intermittent allergic rhinitis","volume":"67","author":"S. Bruhn","year":"2012","journal-title":"Allergy"},{"issue":"5","key":"ref44","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.immuni.2010.05.003","article-title":"Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis","volume":"32","author":"L. Durant","year":"2010","journal-title":"Immunity"},{"issue":"4","key":"ref45","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/nmeth.3799","article-title":"Tissue-specific regulatory circuits reveal variable modular perturbations across complex diseases","volume":"13","author":"D. Marbach","year":"2016","journal-title":"Nat Methods"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1186\/1471-2105-10-262","article-title":"Integrative modeling of transcriptional regulation in response to antirheumatic therapy","volume":"10","author":"M. Hecker","year":"2009","journal-title":"BMC Bioinformatics"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1752-0509-7-1","article-title":"Inference of dynamical gene-regulatory networks based on time-resolved multi-stimuli multi-experiment data applying NetGenerator V2.0","volume":"7","author":"M. Weber","year":"2013","journal-title":"BMC Syst Biol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/1752-0509-6-147","article-title":"The extended TILAR approach: a novel tool for dynamic modeling of the transcription factor network regulating the adaption to in vitro cultivation of murine hepatocytes","volume":"6","author":"S. Vlaic","year":"2012","journal-title":"BMC Syst Biol"},{"issue":"218","key":"ref49","doi-asserted-by":"crossref","first-page":"218ra4","DOI":"10.1126\/scitranslmed.3007410","article-title":"A generally applicable translational strategy identifies S100A4 as a candidate gene in allergy","volume":"6","author":"S. Bruhn","year":"2014","journal-title":"Sci Transl Med"},{"issue":"4","key":"ref50","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.4049\/jimmunol.1200405","article-title":"Tyrosine phosphorylation of c-Maf enhances the expression of IL-4 gene","volume":"189","author":"C.Y. Lai","year":"2012","journal-title":"J Immunol"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1005608","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,7,7]],"date-time":"2017-07-07T00:00:00Z","timestamp":1499385600000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1005608","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T15:27:36Z","timestamp":1539962856000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1005608"}},"subtitle":[],"editor":[{"given":"Thomas","family":"Lengauer","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2017,6,22]]},"references-count":50,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2017,6,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1005608","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/115477","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,22]]}}}