Publication:
Unified modeling of familial mediterranean fever and cryopyrin associated periodic syndromes

dc.contributor.coauthorGül, Ahmet
dc.contributor.departmentDepartment of Chemical and Biological Engineering
dc.contributor.departmentDepartment of Electrical and Electronics Engineering
dc.contributor.departmentGraduate School of Sciences and Engineering
dc.contributor.kuauthorDemir, Alper
dc.contributor.kuauthorErman, Burak
dc.contributor.kuauthorBozkurt, Yasemin
dc.contributor.schoolcollegeinstituteCollege of Engineering
dc.contributor.schoolcollegeinstituteGRADUATE SCHOOL OF SCIENCES AND ENGINEERING
dc.date.accessioned2024-11-09T11:39:35Z
dc.date.issued2015
dc.description.abstractFamilial mediterranean fever (FMF) and Cryopyrin associated periodic syndromes (CAPS) are two prototypical hereditary autoinflammatory diseases, characterized by recurrent episodes of fever and inflammation as a result of mutations in MEFV and NLRP3 genes encoding Pyrin and Cryopyrin proteins, respectively. Pyrin and Cryopyrin play key roles in the multiprotein inflammasome complex assembly, which regulates activity of an enzyme, Caspase 1, and its target cytokine, IL-1 beta. Overproduction of IL-1 beta by Caspase 1 is the main cause of episodic fever and inflammatory findings in FMF and CAPS. We present a unifying dynamical model for FMF and CAPS in the form of coupled nonlinear ordinary differential equations. The model is composed of two subsystems, which capture the interactions and dynamics of the key molecular players and the insults on the immune system. One of the subsystems, which contains a coupled positive-negative feedback motif, captures the dynamics of inflammation formation and regulation. We perform a comprehensive bifurcation analysis of the model and show that it exhibits three modes, capturing the Healthy, FMF, and CAPS cases. The mutations in Pyrin and Cryopyrin are reflected in the values of three parameters in the model. We present extensive simulation results for the model that match clinical observations.
dc.description.fulltextYES
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.openaccessYES
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.sponsorshipKoç University Graduate Fellowship
dc.description.versionPublisher version
dc.description.volume2015
dc.identifier.doi10.1155/2015/893507
dc.identifier.eissn1748-6718
dc.identifier.embargoNO
dc.identifier.filenameinventorynoIR00351
dc.identifier.issn1748-670X
dc.identifier.quartileQ2
dc.identifier.scopus2-s2.0-84935834182
dc.identifier.urihttps://doi.org/10.1155/2015/893507
dc.identifier.urihttps://hdl.handle.net/20.500.14288/124
dc.identifier.wos356728900001
dc.keywordsIl-1 receptor
dc.keywordsInflammasome activation
dc.keywordsGene
dc.keywordsInterleukin-1
dc.keywordsPyrin
dc.keywordsProtein
dc.keywordsDomain
dc.keywordsInhibition
dc.keywordsAntagonist
dc.keywordsCaspase-1
dc.language.isoeng
dc.publisherHindawi
dc.relation.ispartofComputational and Mathematical Methods in Medicine
dc.relation.urihttp://cdm21054.contentdm.oclc.org/cdm/ref/collection/IR/id/1307
dc.subjectMathematical and computational biology
dc.titleUnified modeling of familial mediterranean fever and cryopyrin associated periodic syndromes
dc.typeJournal Article
dspace.entity.typePublication
local.publication.orgunit1GRADUATE SCHOOL OF SCIENCES AND ENGINEERING
local.publication.orgunit1College of Engineering
local.publication.orgunit2Graduate School of Sciences and Engineering
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