{"database":"BioModels","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Pdf":["https://www.ebi.ac.uk/biomodels/model/download/MODEL1412200000?filename=MODEL1412200000.pdf"],"Svg":["https://www.ebi.ac.uk/biomodels/model/download/MODEL1412200000?filename=MODEL1412200000.svg"],"Xml":["https://www.ebi.ac.uk/biomodels/model/download/MODEL1412200000?filename=MODEL1412200000_url.xml","https://www.ebi.ac.uk/biomodels/model/download/MODEL1412200000?filename=MODEL1412200000_urn.xml"],"Other":["https://www.ebi.ac.uk/biomodels/model/download/MODEL1412200000?filename=MODEL1412200000.sci","https://www.ebi.ac.uk/biomodels/model/download/MODEL1412200000?filename=MODEL1412200000.png","https://www.ebi.ac.uk/biomodels/model/download/MODEL1412200000?filename=MODEL1412200000.vcml"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"submitter":["Soheil Rastgou Talemi"],"curationStatus":["Non-curated"],"modellingApproach":["ordinary differential equation model"],"levelVersion":["L2V4"],"full_dataset_link":["https://www.ebi.ac.uk/biomodels/MODEL1412200000"],"publication_pubmed":["26359627"],"isPrivate":["false"],"repository":["BioModels"],"modelFormat":["SBML"],"omics_type":["Models"],"tokenised_name":["Talemi2015   Persistent telomere associated DNA damage foci (TAF), a measure to predict cancer risks"],"publication_year":["2015"],"submissionId":["MODEL1412200000"],"publication_authors":["Soheil Rastgou Talemi, Gabriel Kollarovic, Anastasiya Lapytsko, Jörg Schaber"],"first_author":["Soheil Rastgou Talemi"],"publication":["26359627,\n                            Mathematical modelling has been instrumental to understand kinetics of radiation-induced DNA damage repair and associated secondary cancer risk. The widely accepted two-lesion kinetic (TLK) model assumes two kinds of double strand breaks, simple and complex ones, with different repair rates. Recently, persistent DNA damage associated with telomeres was reported as a new kind of DNA damage. We therefore extended existing versions of the TLK model by new categories of DNA damage and re-evaluated those models using extensive data. We subjected different versions of the TLK model to a rigorous model discrimination approach. This enabled us to robustly select a best approximating parsimonious model that can both recapitulate and predict transient and persistent DNA damage after ionizing radiation. Models and data argue for i) nonlinear dose-damage relationships, and ii) negligible saturation of repair kinetics even for high doses. Additionally, we show that simulated radiation-induced persistent telomere-associated DNA damage foci (TAF) can be used to predict excess relative risk (ERR) of developing secondary leukemia after fractionated radiotherapy. We suggest that TAF may serve as an additional measure to predict cancer risk after radiotherapy using high dose rates. This may improve predicting risk-dose dependency of ionizing radiation especially for long-term therapies.. null, 5.\n                            Institute for Experimental Internal Medicine, Medical Faculty, Otto von Guericke University, Magdeburg, Germany."],"submitter_mail":["soheil.rastgou@med.ovgu.de"],"submitter_affiliation":["Otto von Guericke University"],"pubmed_abstract":["Mathematical modelling has been instrumental to understand kinetics of radiation-induced DNA damage repair and associated secondary cancer risk. The widely accepted two-lesion kinetic (TLK) model assumes two kinds of double strand breaks, simple and complex ones, with different repair rates. Recently, persistent DNA damage associated with telomeres was reported as a new kind of DNA damage. We therefore extended existing versions of the TLK model by new categories of DNA damage and re-evaluated those models using extensive data. We subjected different versions of the TLK model to a rigorous model discrimination approach. This enabled us to robustly select a best approximating parsimonious model that can both recapitulate and predict transient and persistent DNA damage after ionizing radiation. Models and data argue for i) nonlinear dose-damage relationships, and ii) negligible saturation of repair kinetics even for high doses. Additionally, we show that simulated radiation-induced persistent telomere-associated DNA damage foci (TAF) can be used to predict excess relative risk (ERR) of developing secondary leukemia after fractionated radiotherapy. We suggest that TAF may serve as an additional measure to predict cancer risk after radiotherapy using high dose rates. This may improve predicting risk-dose dependency of ionizing radiation especially for long-term therapies."],"pubmed_title":["Development of a robust DNA damage model including persistent telomere-associated damage with application to secondary cancer risk assessment."],"pubmed_authors":["Rastgou Talemi Soheil S, Kollarovic Gabriel G, Lapytsko Anastasiya A, Schaber Jörg J"],"additional_accession":[]},"is_claimable":false,"name":"Talemi2015 - Persistent telomere-associated DNA damage foci (TAF), a measure to predict cancer risks","description":"\n      \n        A Robust Model of DNA Damage Dynamics.\nRasgou Talemi and Schaber, 12.20.2014.\n\n      \n    ","dates":{"last_modification":"2016-02-11","publication":"2016-02-11","submission":"2014-12-20"},"accession":"MODEL1412200000","cross_references":{"pubmed":["26359627"],"biomodels__db":["MODEL1412200000"]}}