TY - JOUR T1 - Modelling <em>TERT</em> regulation across 19 different cancer types based on the MIPRIP 2.0 gene regulatory network approach JF - bioRxiv DO - 10.1101/513259 SP - 513259 AU - Alexandra M. Poos AU - Theresa Kordaß AU - Amol Kolte AU - Volker Ast AU - Marcus Oswald AU - Karsten Rippe AU - Rainer König Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/01/13/513259.abstract N2 - Background Reactivation of the telomerase reverse transcriptase gene TERT is a central feature for the unlimited proliferation potential of the majority of cancers but the underlying regulatory processes are only partly understood.Results We assembled regulator binding information from different sources to construct a generic human and mouse regulatory network. Advancing our “Mixed Integer linear Programming based Regulatory Interaction Predictor” (MIPRIP) approach, we identified the most common and cancer-type specific regulators of TERT across 19 different human cancers. The results were validated by using the well-known TERT regulation by the ETS1 transcription factor in a subset of melanomas with mutations in the TERT promoter.Conclusion Our improved MIPRIP2 R-package and the associated generic regulatory networks are freely available at https://github.com/network-modeling/MIPRIP. MIPRIP 2.0 identified both common as well as tumor type specific regulators of TERT. The software can be easily applied to transcriptome datasets to predict gene regulation for any gene and disease/condition under investigation.MIPRIPMixed Integer linear Programming based Regulatory Interaction PredictorTMMtelomere maintenance mechanismTFtranscription factorGRNgene regulatory networkChIPChromatin immunoprecipitationTCGAThe Cancer Genome AtlasSKCMskin cutaneous melanomaOVovarian serous cystadenocarcinomaCESCcervical cancerTHYMthymomaTGCTtesticular germ cell cancerPRADprostate adenocarcinomaPAADpancreatic ductal adenocarcinomaBRCAbreast cancerISMARAIntegrated Motif Activity Response AnalysisEMSAelectrophoretic shift assayMILPMixed Integer Linear ProgrammingGDACGenome Data Analysis CenterRSEMaccurate transcript quantification from RNA-Seq data with or without a reference genomeChEAChIP Enrichment AnalysisHTRIdbHuman Transcriptional Regulation Interactions databaseTBAtotal binding affinityesedge strengthFPKMfragments per kilobase of exon model per million reads mappedE-valueexpected valueTERTTelomerase reverse transcriptaseARandrogen receptorETSE-twenty six ER -