Abstract
With next generation sequencing thousands of virus and viral vector integration genome targets are now under investigation to uncover specific integration preferences and to define clusters of integration, termed common integration sites (CIS), that may allow to assess gene therapy safety or to detect disease related genomic features such as oncogenes.Here, we addressed the challenge to: 1) define the notion of CIS on graph models, 2) demonstrate that the structure of CIS enters in the category of scale-free networks and 3) show that our network approach analyzes CIS dynamically in an integrated systems biology framework using the Retroviral Transposon Tagged Cancer Gene Database (RTCGD) as a testing dataset.
Highlights
We addressed the challenge to: 1) define the notion of CIS on graph models, 2) demonstrate that the structure of CIS enters in the category of scale-free networks and 3) show that our network approach analyzes CIS dynamically in an integrated systems biology framework using the Retroviral Transposon Tagged Cancer Gene Database (RTCGD) as a testing dataset
Viral vector integration is a process exploited in gene therapy (GT) to correct defective cells of an individual and to drive the health status from the pathological condition to a normal one [1,2,3,4,5,6]
Large insertional mutagenesis screenings are used to assess the safety of the treatment in clinical GT, to design safer GT protocols and to discover new disease candidate genes [12,13,14,15,16]
Summary
Raffaele Fronza a,⁎, Alessandro Vasciaveo a,b, Alfredo Benso b, Manfred Schmidt a a Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany b Department of Control and Computer Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy article info. Article history: Received 27 April 2015 Received in revised form 20 October 2015 Accepted 23 October 2015 Available online 30 November 2015. With generation sequencing thousands of virus and viral vector integration genome targets are under investigation to uncover specific integration preferences and to define clusters of integration, termed common integration sites (CIS), that may allow to assess gene therapy safety or to detect disease related genomic features such as oncogenes. We addressed the challenge to: 1) define the notion of CIS on graph models, 2) demonstrate that the structure of CIS enters in the category of scale-free networks and 3) show that our network approach analyzes CIS dynamically in an integrated systems biology framework using the Retroviral Transposon Tagged Cancer Gene Database (RTCGD) as a testing dataset
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