{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T11:19:52Z","timestamp":1771067992492,"version":"3.50.1"},"reference-count":77,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2013,9,26]],"date-time":"2013-09-26T00:00:00Z","timestamp":1380153600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1003217","type":"journal-article","created":{"date-parts":[[2013,9,26]],"date-time":"2013-09-26T21:13:13Z","timestamp":1380229993000},"page":"e1003217","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Modeling the Effect of APC Truncation on Destruction Complex Function in Colorectal Cancer Cells"],"prefix":"10.1371","volume":"9","author":[{"given":"Dipak","family":"Barua","sequence":"first","affiliation":[]},{"given":"William S.","family":"Hlavacek","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2013,9,26]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.cell.2006.10.018","article-title":"Wnt\/<italic>\u03b2<\/italic>\u2013catenin signaling in development and disease","volume":"127","author":"H Clevers","year":"2006","journal-title":"Cell"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.1038\/emboj.2012.146","article-title":"Three decades of Wnt: a personal perspective on how a scientific field developed","volume":"31","author":"R Nusse","year":"2012","journal-title":"EMBO J"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"2748","DOI":"10.1016\/j.yexcr.2011.08.010","article-title":"Wnt signaling and colon tumorigenesis \u2014 a view from the periphery","volume":"317","author":"A Burgess","year":"2011","journal-title":"Exp Cell Res"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/382638a0","article-title":"Functional interaction of <italic>\u03b2<\/italic>\u2013catenin with the transcription factor LEF-1","volume":"382","author":"J Behrens","year":"1996","journal-title":"Nature"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/S0092-8674(00)80112-9","article-title":"XTcf-3 transcription factor mediates <italic>\u03b2<\/italic>\u2013catenin-induced axis formation in Xenopus embryos","volume":"86","author":"M Molenaar","year":"1996","journal-title":"Cell"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/S0092-8674(00)81925-X","article-title":"Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF","volume":"88","author":"M van de Wetering","year":"1997","journal-title":"Cell"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"4238","DOI":"10.1128\/MCB.20.12.4238-4252.2000","article-title":"Differential mechanisms of LEF\/TCF family-dependent transcriptional activation by <italic>\u03b2<\/italic>\u2013catenin and plakoglobin","volume":"20","author":"J Zhurinsky","year":"2000","journal-title":"Mol Cell Biol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1126\/science.287.5458.1606","article-title":"Wnt signaling in oncogenesis and embryogenesis\u2014a look outside the nucleus","volume":"287","author":"M Peifer","year":"2000","journal-title":"Science"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"7482","DOI":"10.1038\/sj.onc.1210055","article-title":"<italic>\u03b2<\/italic>\u2013catenin destruction complex: insights and questions from a structural perspective","volume":"25","author":"D Kimelman","year":"2006","journal-title":"Oncogene"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"a007898","DOI":"10.1101\/cshperspect.a007898","article-title":"The <italic>\u03b2<\/italic>\u2013catenin destruction complex","volume":"5","author":"JL Stamos","year":"2013","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1093\/emboj\/cdg068","article-title":"Structural basis for recruitment of glycogen synthase kinase 3<italic>\u03b2<\/italic> to the axin-APC scaffold complex","volume":"22","author":"R Dajani","year":"2003","journal-title":"EMBO J"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/S0092-8674(02)00685-2","article-title":"Control of <italic>\u03b2<\/italic>\u2013catenin phosphorylation\/degradation by a dual-kinase mechanism","volume":"108","author":"C Liu","year":"2002","journal-title":"Cell"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.tibs.2009.10.002","article-title":"GSK3: a multifaceted kinase in Wnt signaling","volume":"35","author":"D Wu","year":"2010","journal-title":"Trends Biochem Sci"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1126\/science.275.5307.1790","article-title":"Stabilization of <italic>\u03b2<\/italic>\u2013catenin by genetic defects in melanoma cell lines","volume":"275","author":"B Rubinfeld","year":"1997","journal-title":"Science"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"3797","DOI":"10.1093\/emboj\/16.13.3797","article-title":"<italic>\u03b2<\/italic>\u2013catenin is a target for the ubiquitin-proteasome pathway","volume":"16","author":"H Aberle","year":"1997","journal-title":"EMBO J"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/S0960-9822(03)00370-1","article-title":"A role of Dishevelled in relocating Axin to the plasma membrane during Wingless signaling","volume":"13","author":"A Cliffe","year":"2003","journal-title":"Curr Biol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1471-2121-4-4","article-title":"Wnt\/Wingless signaling through <italic>\u03b2<\/italic>\u2013catenin requires the function of both LRP\/Arrow and frizzled classes of receptors","volume":"4","author":"L Schweizer","year":"2003","journal-title":"BMC Cell Biol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"5103","DOI":"10.1242\/dev.01318","article-title":"Wnt signals across the plasma membrane to activate the <italic>\u03b2<\/italic>\u2013catenin pathway by forming oligomers containing its receptors, Frizzled and LRP","volume":"131","author":"F Cong","year":"2004","journal-title":"Development"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.cell.2012.05.002","article-title":"Wnt signaling through inhibition of <italic>\u03b2<\/italic>\u2013catenin degradation in an intact Axin1 complex","volume":"149","author":"VSW Li","year":"2012","journal-title":"Cell"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1126\/science.1228734","article-title":"Kinetic responses of <italic>\u03b2<\/italic>\u2013catenin specify the sites of Wnt control","volume":"338","author":"AR Hern\u00e1ndez","year":"2012","journal-title":"Science"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1056\/NEJMra0804588","article-title":"Molecular basis of colorectal cancer","volume":"361","author":"SD Markowitz","year":"2009","journal-title":"N Engl J Med"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1101\/gad.1142603","article-title":"Crystal structure of a <italic>\u03b2<\/italic>\u2013catenin\/axin complex suggests a mechanism for the <italic>\u03b2<\/italic>\u2013catenin destruction complex","volume":"17","author":"Y Xing","year":"2003","journal-title":"Genes Dev"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"14090","DOI":"10.1074\/jbc.274.20.14090","article-title":"Functional domains of axin. Importance of the C terminus as an oligomerization domain","volume":"274","author":"C Sakanaka","year":"1999","journal-title":"J Biol Chem"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.molcel.2004.08.001","article-title":"Crystal structure of a <italic>\u03b2<\/italic>\u2013catenin\/APC complex reveals a critical role for APC phosphorylation in APC function","volume":"15","author":"Y Xing","year":"2004","journal-title":"Mol Cell"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.jmb.2006.04.064","article-title":"The third 20 amino acid repeat is the tightest binding site of APC for <italic>\u03b2<\/italic>\u2013catenin","volume":"360","author":"J Liu","year":"2006","journal-title":"J Mol Biol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"6203","DOI":"10.1093\/emboj\/20.22.6203","article-title":"Molecular mechanisms of <italic>\u03b2<\/italic>\u2013catenin recognition by adenomatous polyposis coli revealed by the structure of an APC-<italic>\u03b2<\/italic>\u2013catenin complex","volume":"20","author":"K Eklof Spink","year":"2001","journal-title":"EMBO J"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1093\/emboj\/19.10.2270","article-title":"Structural basis of the Axin-adenomatous polyposis coli interaction","volume":"19","author":"KE Spink","year":"2000","journal-title":"EMBO J"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"7147","DOI":"10.1128\/MCB.19.10.7147","article-title":"Regulation of glycogen synthase kinase 3<italic>\u03b2<\/italic> and downstream Wnt signaling by axin","volume":"19","author":"CM Hedgepeth","year":"1999","journal-title":"Mol Cell Biol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/jcb.20350","article-title":"Basic region of residues 228\u2013231 of protein kinase CK1<italic>\u03b1<\/italic> is involved in its interaction with axin: binding to axin does not affect the kinase activity","volume":"94","author":"P Sobrado","year":"2005","journal-title":"J Cell Biochem"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.molcel.2004.08.010","article-title":"Mechanism of phosphorylation-dependent binding of APC to <italic>\u03b2<\/italic>\u2013catenin and its role in <italic>\u03b2<\/italic>\u2013catenin degradation","volume":"15","author":"NC Ha","year":"2004","journal-title":"Mol Cell"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"3046","DOI":"10.1073\/pnas.92.7.3046","article-title":"Regulation of intracellular <italic>\u03b2<\/italic>\u2013catenin levels by the adenomatous polyposis coli (APC) tumor-suppressor protein","volume":"92","author":"S Munemitsu","year":"1995","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.bbrc.2007.03.117","article-title":"Axin-independent phosphorylation of APC controls <italic>\u03b2<\/italic>\u2013catenin signaling via cytoplasmic retention of <italic>\u03b2<\/italic>\u2013catenin","volume":"357","author":"E Seo","year":"2007","journal-title":"Biochem Biophys Res Commun"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"17751","DOI":"10.1074\/jbc.M600831200","article-title":"Adenomatous polyposis coli (APC) differentially regulates <italic>\u03b2<\/italic>\u2013catenin phosphorylation and ubiquitination in colon cancer cells","volume":"281","author":"J Yang","year":"2006","journal-title":"J Biol Chem"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1242\/jcs.00862","article-title":"Restoration of full-length adenomatous polyposis coli (APC) protein in a colon cancer cell line enhances cell adhesion","volume":"117","author":"MC Faux","year":"2004","journal-title":"J Cell Sci"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1242\/jcs.002956","article-title":"Dynamic recruitment of axin by Dishevelled protein assemblies","volume":"120","author":"T Schwarz-Romond","year":"2007","journal-title":"J Cell Sci"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"5808","DOI":"10.1038\/onc.2008.205","article-title":"Recruitment of ademonatous polyposis coli and <italic>\u03b2<\/italic>\u2013catenin to axin-puncta","volume":"27","author":"M Faux","year":"2008","journal-title":"Oncogene"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"re6","DOI":"10.1126\/stke.3442006re6","article-title":"Rules for modeling signal-transduction systems","volume":"2006","author":"WS Hlavacek","year":"2006","journal-title":"Sci STKE"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/cplx.20074","article-title":"Rule-based modeling of biochemical networks","volume":"10","author":"JR Faeder","year":"2005","journal-title":"Complexity"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/978-1-59745-525-1_5","article-title":"Rule-based modeling of biochemical systems with BioNetGen","volume":"500","author":"JR Faeder","year":"2009","journal-title":"Methods Mol Biol"},{"key":"ref40","doi-asserted-by":"crossref","unstructured":"Chylek LA, Stites EC, Posner RG, Hlavacek WS (2013) Innovations of the rule-based modeling approach. In: Prokop A, Csuk\u00e1s B, Editors. Systems Biology: Integrative Biology and Simulation Tools, Volume 1. Springer.","DOI":"10.1007\/978-94-007-6803-1_9"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1002\/bit.10842","article-title":"The complexity of complexes in signal transduction","volume":"84","author":"WS Hlavacek","year":"2003","journal-title":"Biotechnol Bioeng"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1039\/c1mb05077j","article-title":"Guidelines for visualizing and annotating rule-based models","volume":"7","author":"LA Chylek","year":"2011","journal-title":"Mol BioSyst"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"10823","DOI":"10.1074\/jbc.273.18.10823","article-title":"Axin, a negative regulator of the wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates the stabilization of <italic>\u03b2<\/italic>\u2013catenin","volume":"273","author":"S Kishida","year":"1998","journal-title":"J Biol Chem"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj3590001","article-title":"GSK3 takes centre stage more than 20 years after its discovery","volume":"359","author":"S Frame","year":"2001","journal-title":"Biochem J"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"39037","DOI":"10.1074\/jbc.M105148200","article-title":"Axin-dependent phosphorylation of the adenomatous polyposis coli protein mediated by casein kinase 1<italic>\u03b5<\/italic>","volume":"276","author":"B Rubinfeld","year":"2001","journal-title":"J Biol Chem"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/sj.onc.1203359","article-title":"GSK-3<italic>\u03b2<\/italic>-dependent phosphorylation of adenomatous polyposis coli gene product can be modulated by <italic>\u03b2<\/italic>\u2013catenin and protein phosphatase 2A complexed with Axin","volume":"19","author":"S Ikeda","year":"2000","journal-title":"Oncogene"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/0019-2791(72)90097-3","article-title":"The influence of polyvalency on the binding properties of antibodies","volume":"9","author":"DM Crothers","year":"1972","journal-title":"Immunochemistry"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.1073\/pnas.90.7.2846","article-title":"The APC gene product in normal and tumor cells","volume":"90","author":"KJ Smith","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.mbs.2011.06.003","article-title":"Scaffold-mediated nucleation of protein signaling complexes: elementary principles","volume":"232","author":"J Yang","year":"2011","journal-title":"Math Biosci"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"6092","DOI":"10.1021\/ja311795d","article-title":"A comprehensive mathematical model for three-body binding equilibria","volume":"135","author":"EF Douglass Jr","year":"2013","journal-title":"J Am Chem Soc"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1126\/science.280.5363.596","article-title":"Functional interaction of an axin homolog, conductin, with <italic>\u03b2<\/italic>\u2013catenin, APC, and GSK3<italic>\u03b2<\/italic>","volume":"280","author":"J Behrens","year":"1998","journal-title":"Science"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S0960-9822(98)70226-X","article-title":"Downregulation of <italic>\u03b2<\/italic>\u2013catenin by human Axin and its association with the APC tumor suppressor, <italic>\u03b2<\/italic>\u2013catenin and GSK3<italic>\u03b2<\/italic>","volume":"8","author":"MJ Hart","year":"1998","journal-title":"Curr Biol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"E10","DOI":"10.1371\/journal.pbio.0000010","article-title":"The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathway","volume":"1","author":"E Lee","year":"2003","journal-title":"PLoS Biol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/S0092-8674(00)00192-6","article-title":"Crystal structure of a <italic>\u03b2<\/italic>\u2013catenin\/Tcf complex","volume":"103","author":"TA Graham","year":"2000","journal-title":"Cell"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1038\/79039","article-title":"Hot spots in <italic>\u03b2<\/italic>\u2013catenin for interactions with LEF-1, conductin and APC","volume":"7","author":"JP von Kries","year":"2000","journal-title":"Nat Struct Biol"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1110\/ps.9.3.570","article-title":"Alternative modes of binding of proteins with tandem SH2 domains","volume":"9","author":"R O'Brien","year":"2000","journal-title":"Protein Sci"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"7338","DOI":"10.1074\/jbc.M708359200","article-title":"Computational models of tandem SRC homology 2 domain interactions and application to phosphoinositide 3-kinase","volume":"283","author":"D Barua","year":"2008","journal-title":"J Biol Chem"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1146\/annurev.biophys.26.1.259","article-title":"Modular peptide recognition domains in eukaryotic signaling","volume":"26","author":"J Kuriyan","year":"1997","journal-title":"Annu Rev Biophys Biomol Struct"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"e31882","DOI":"10.1371\/journal.pone.0031882","article-title":"Wnt signalling pathway parameters for mammalian cells","volume":"7","author":"CW Tan","year":"2012","journal-title":"PLOS ONE"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1063\/1.1747547","article-title":"Intramolecular reaction in polycondensations. I. The theory of linear systems","volume":"18","author":"H Jacobson","year":"1950","journal-title":"J Chem Phys"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/nrm806","article-title":"The subcellular destinations of APC proteins","volume":"3","author":"M Bienz","year":"2002","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/35023605","article-title":"Nuclear-cytoplasmic shuttling of APC regulates <italic>\u03b2<\/italic>\u2013catenin subcellular localization and turnover","volume":"2","author":"BR Henderson","year":"2000","journal-title":"Nat Cell Biol"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/35023016","article-title":"The APC tumour suppressor has a nuclear export function","volume":"406","author":"R Rosin-Arbesfeld","year":"2000","journal-title":"Nature"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1083\/jcb.127.6.2061","article-title":"E-cadherin and APC compete for the interaction with <italic>\u03b2<\/italic>\u2013catenin and the cytoskeleton","volume":"127","author":"J H\u00fclsken","year":"1994","journal-title":"J Cell Biol"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"5303","DOI":"10.1038\/sj.onc.1203939","article-title":"IC261, a specific inhibitor of the protein kinases casein kinase 1-delta and -epsilon, triggers the mitotic checkpoint and induces p53-dependent postmitotic effects","volume":"19","author":"L Behrend","year":"2000","journal-title":"Oncogene"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1124\/jpet.107.122846","article-title":"An inhibitor of casein kinase I<italic>\u03b5<\/italic> induces phase delays in circadian rhythms under free-running and entrained conditions","volume":"322","author":"L Badura","year":"2007","journal-title":"J Pharmacol Exp Ther"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1124\/jpet.109.151415","article-title":"Selective inhibition of casein kinase 1<italic>\u03b5<\/italic> minimally alters circadian clock period","volume":"330","author":"K Walton","year":"2009","journal-title":"J Pharmacol Exp Ther"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1093\/emboj\/17.5.1371","article-title":"Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3<italic>\u03b2<\/italic> and <italic>\u03b2<\/italic>\u2013catenin and promotes GSK-3<italic>\u03b2<\/italic>-dependent phosphorylation of <italic>\u03b2<\/italic>\u2013catenin","volume":"17","author":"S Ikeda","year":"1998","journal-title":"EMBO J"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1371\/journal.pcbi.0030189","article-title":"Universally sloppy parameter sensitivities in systems biology models","volume":"3","author":"RN Gutenkunst","year":"2007","journal-title":"PLoS Comput Biol"},{"key":"ref70","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1093\/bioinformatics\/bth378","article-title":"BioNetGen: software for rule-based modeling of signal transduction based on the interactions of molecular domains","volume":"20","author":"ML Blinov","year":"2004","journal-title":"Bioinformatics"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1093\/bioinformatics\/btr197","article-title":"RuleBender: a visual interface for rule-based modeling","volume":"27","author":"W Xu","year":"2011","journal-title":"Bioinformatics"},{"key":"ref72","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1063\/1.4822377","article-title":"CVODE, a stiff\/nonstiff ODE solver in C","volume":"10","author":"S Cohen","year":"1996","journal-title":"Comp Phys"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1145\/1089014.1089020","article-title":"SUNDIALS: Suite of nonlinear and differential\/algebraic equation solvers","volume":"31","author":"A Hindmarsh","year":"2005","journal-title":"ACM Trans Math Softw"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.1242\/jcs.115.13.2771","article-title":"Regulation of S33\/S37 phosphorylated <italic>\u03b2<\/italic>\u2013catenin in normal and transformed cells","volume":"115","author":"E Sadot","year":"2002","journal-title":"J Cell Sci"},{"key":"ref75","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/1471-2105-10-136","article-title":"Infrastructure for the life sciences: design and implementation of the UniProt website","volume":"10","author":"E Jain","year":"2009","journal-title":"BMC Bioinformatics"},{"key":"ref76","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/humu.21466","article-title":"A new face and new challenges for Online Medelian Inheritance in Man (OMIM)","volume":"32","author":"J Amberger","year":"2011","journal-title":"Hum Mut"},{"key":"ref77","doi-asserted-by":"crossref","first-page":"D211","DOI":"10.1093\/nar\/gkp985","article-title":"The Pfam protein families database","volume":"38","author":"RD Finn","year":"2010","journal-title":"Nucleic Acids Res"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003217","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,6]],"date-time":"2022-03-06T23:32:52Z","timestamp":1646609572000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003217"}},"subtitle":[],"editor":[{"given":"Stanislav","family":"Shvartsman","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2013,9,26]]},"references-count":77,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2013,9,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1003217","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,9,26]]}}}