Publication:
Identification of novel components of target-of-rapamycin signaling pathway by network-based multi-omics integrative analysis

dc.contributor.coauthorEke, Elif Dereli
dc.contributor.coauthorArga, Kazim Yalcin
dc.contributor.coauthorDikicioglu, Duygu
dc.contributor.coauthorEraslan, Serpil
dc.contributor.coauthorErkol, Emir
dc.contributor.coauthorCelik, Arzu
dc.contributor.coauthorKirdar, Betul
dc.contributor.coauthorDi Camillo, Barbara
dc.contributor.departmentKUTTAM (Koç University Research Center for Translational Medicine)
dc.contributor.departmentSchool of Medicine
dc.contributor.kuauthorEraslan, Serpil
dc.contributor.schoolcollegeinstituteResearch Center
dc.contributor.schoolcollegeinstituteSCHOOL OF MEDICINE
dc.date.accessioned2024-11-09T23:19:20Z
dc.date.issued2019
dc.description.abstractTarget of rapamycin (TOR) is a major signaling pathway and regulator of cell growth. TOR serves as a hub of many signaling routes, and is implicated in the pathophysiology of numerous human diseases, including cancer, diabetes, and neurodegeneration. Therefore, elucidation of unknown components of TOR signaling that could serve as potential biomarkers and drug targets has a great clinical importance. In this study, our aim is to integrate transcriptomics, interactomics, and regulomics data in Saccharomyces cerevisiae using a network-based multiomics approach to enlighten previously unidentified, potential components of TOR signaling. We constructed the TOR-signaling protein interaction network, which was used as a template to search for TOR-mediated rapamycin and caffeine signaling paths. We scored the paths passing from at least one component of TOR Complex 1 or 2 (TORC1/TORC2) using the co-expression levels of the genes in the transcriptome data of the cells grown in the presence of rapamycin or caffeine. The resultant network revealed seven hitherto unannotated proteins, namely, Atg14p, Rim20p, Ret2p, Spt21p, Ylr257wp, Ymr295cp, and Ygr017wp, as potential components of TOR-mediated rapamycin and caffeine signaling in yeast. Among these proteins, we suggest further deciphering of the role of Ylr257wp will be particularly informative in the future because it was the only protein whose removal from the constructed network hindered the signal transduction to the TORC1 effector kinase Npr1p. In conclusion, this study underlines the value of network-based multiomics integrative data analysis in discovering previously unidentified components of the signaling networks by revealing potential components of TOR signaling for future experimental validation.
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue5
dc.description.openaccessYES
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.sponsorshipMarmara University Research Fund (BAPKO) [FEN-A-091116-0496]
dc.description.sponsorshipUniversity of Padova Junior Project Grants: "Dynamic Modeling of TOR signaling pathway through systems biology approaches" [TUBITAK110M692]
dc.description.sponsorshipTurkish State Planning Organization [DPT-09 K120520]
dc.description.sponsorshipBoazici University Research Fund 1932 project
dc.description.sponsorshipLeverhulme Trust [ECF-2016-681] This work was supported by Marmara University Research Fund (BAPKO) through FEN-A-091116-0496 project, University of Padova Junior Project Grants: "Dynamic Modeling of TOR signaling pathway through systems biology approaches," TUBITAK110M692 project, Turkish State Planning Organization DPT-09 K120520 project, and the Boazici University Research Fund 1932 project. Duygu Dikiciolu would like to thank the Leverhulme Trust (ECF-2016-681) and the Isaac Newton Trust. The authors thank Tiziana Sanavia for comments and assistance in this study.
dc.description.volume23
dc.identifier.doi10.1089/omi.2019.0021
dc.identifier.eissn1557-8100
dc.identifier.issn1536-2310
dc.identifier.quartileQ2
dc.identifier.scopus2-s2.0-85065881694
dc.identifier.urihttps://doi.org/10.1089/omi.2019.0021
dc.identifier.urihttps://hdl.handle.net/20.500.14288/10536
dc.identifier.wos464560900001
dc.keywordsDrug targets
dc.keywordsTarget of rapamycin (TOR) signaling
dc.keywordsBiomarkers
dc.keywordsMultiomics
dc.keywordsCaffeine
dc.keywordsNetwork-based analysis tor function
dc.keywordsGrowth
dc.keywordsAutophagy
dc.keywordsDatabase
dc.keywordsReveals
dc.keywordsMTORC2
dc.keywordsEnhancement
dc.keywordsInformation
dc.keywordsMetabolism
dc.keywordsComplexes
dc.language.isoeng
dc.publisherMary Ann Liebert, Inc.
dc.relation.ispartofOmics-A Journal of Integrative Biology
dc.subjectBiotechnology
dc.subjectApplied microbiology
dc.subjectGenetics
dc.subjectHeredity
dc.titleIdentification of novel components of target-of-rapamycin signaling pathway by network-based multi-omics integrative analysis
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorEraslan, Serpil
local.publication.orgunit1SCHOOL OF MEDICINE
local.publication.orgunit1Research Center
local.publication.orgunit2KUTTAM (Koç University Research Center for Translational Medicine)
local.publication.orgunit2School of Medicine
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relation.isOrgUnitOfPublication.latestForDiscovery91bbe15d-017f-446b-b102-ce755523d939
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