Complex Network Analysis of CA3 Transcriptome Reveals Pathogenic and Compensatory Pathways in Refractory Temporal Lobe Epilepsy

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorBANDO, Silvia Yumi
dc.contributor.authorSILVA, Filipi Nascimento
dc.contributor.authorCOSTA, Luciano Da Fontoura
dc.contributor.authorSILVA, Alexandre V.
dc.contributor.authorPIMENTEL-SILVA, Luciana R.
dc.contributor.authorCASTRO, Luiz H. M.
dc.contributor.authorWEN, Hung-Tzu
dc.contributor.authorAMARO JR., Edson
dc.contributor.authorMOREIRA-FILHO, Carlos Alberto
dc.date.accessioned2014-01-28T22:20:08Z
dc.date.available2014-01-28T22:20:08Z
dc.date.issued2013
dc.description.abstractWe previously described - studying transcriptional signatures of hippocampal CA3 explants - that febrile (FS) and afebrile (NFS) forms of refractory mesial temporal lobe epilepsy constitute two distinct genomic phenotypes. That network analysis was based on a limited number (hundreds) of differentially expressed genes (DE networks) among a large set of valid transcripts (close to two tens of thousands). Here we developed a methodology for complex network visualization (3D) and analysis that allows the categorization of network nodes according to distinct hierarchical levels of gene-gene connections (node degree) and of interconnection between node neighbors (concentric node degree). Hubs are highly connected nodes, VIPs have low node degree but connect only with hubs, and high-hubs have VIP status and high overall number of connections. Studying the whole set of CA3 valid transcripts we: i) obtained complete transcriptional networks (CO) for FS and NFS phenotypic groups; ii) examined how CO and DE networks are related; iii) characterized genomic and molecular mechanisms underlying FS and NFS phenotypes, identifying potential novel targets for therapeutic interventions. We found that: i) DE hubs and VIPs are evenly distributed inside the CO networks; ii) most DE hubs and VIPs are related to synaptic transmission and neuronal excitability whereas most CO hubs, VIPs and high hubs are related to neuronal differentiation, homeostasis and neuroprotection, indicating compensatory mechanisms. Complex network visualization and analysis is a useful tool for systems biology approaches to multifactorial diseases. Network centrality observed for hubs, VIPs and high hubs of CO networks, is consistent with the network disease model, where a group of nodes whose perturbation leads to a disease phenotype occupies a central position in the network. Conceivably, the chance for exerting therapeutic effects through the modulation of particular genes will be higher if these genes are highly interconnected in transcriptional networks.
dc.description.indexMEDLINE
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2009/53443-1, 2005/56446-0, 2005/00587-5, 2011/50761-2]
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [305635/2009-3, 301303/06-1, 573583/2008-0]
dc.description.sponsorshipCenters of Excellence Program (PRONEX-MCT/CNPq) (FAPESP) [2011/50761-2]
dc.identifier.citationPLOS ONE, v.8, n.11, article ID e79913, 17p, 2013
dc.identifier.doi10.1371/journal.pone.0079913
dc.identifier.issn1932-6203
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/4025
dc.language.isoeng
dc.publisherPUBLIC LIBRARY SCIENCE
dc.relation.ispartofPlos One
dc.rightsopenAccess
dc.rights.holderCopyright PUBLIC LIBRARY SCIENCE
dc.subject.otherg-protein gamma(3)
dc.subject.othersynaptic plasticity
dc.subject.otherfebrile seizures
dc.subject.otherhistone deacetylase
dc.subject.otherstriatal plasticity
dc.subject.othermus81 endonuclease
dc.subject.otherneuronal motility
dc.subject.otherpyramidal neurons
dc.subject.othercell dispersion
dc.subject.othersocial networks
dc.subject.wosMultidisciplinary Sciences
dc.titleComplex Network Analysis of CA3 Transcriptome Reveals Pathogenic and Compensatory Pathways in Refractory Temporal Lobe Epilepsy
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.author.externalSILVA, Filipi Nascimento:Univ Sao Paulo, Inst Fis Sao Carlos, Sao Carlos, SP, Brazil
hcfmusp.author.externalCOSTA, Luciano Da Fontoura:Univ Sao Paulo, Inst Fis Sao Carlos, Sao Carlos, SP, Brazil
hcfmusp.author.externalSILVA, Alexandre V.:Univ Fed Sao Paulo, Dept Biosci, Santos, SP, Brazil
hcfmusp.author.externalPIMENTEL-SILVA, Luciana R.:Univ Fed Sao Paulo, Dept Biosci, Santos, SP, Brazil
hcfmusp.citation.scopus20
hcfmusp.contributor.author-fmusphcSILVIA YUMI BANDO TAKAHARA
hcfmusp.contributor.author-fmusphcLUIZ HENRIQUE MARTINS CASTRO
hcfmusp.contributor.author-fmusphcWEN HUNG TZU
hcfmusp.contributor.author-fmusphcEDSON AMARO JUNIOR
hcfmusp.contributor.author-fmusphcCARLOS ALBERTO MOREIRA FILHO
hcfmusp.description.articlenumbere79913
hcfmusp.description.issue11
hcfmusp.description.volume8
hcfmusp.origemWOS
hcfmusp.origem.pubmed24278214
hcfmusp.origem.scopus2-s2.0-84896730655
hcfmusp.origem.wosWOS:000327539800032
hcfmusp.publisher.citySAN FRANCISCO
hcfmusp.publisher.countryUSA
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