Coherence analysis discriminates between retroviral integration patterns in CD34+ cells transduced under differing clinical trial conditions

摘要: Unequivocal demonstration of the therapeutic utility γ-retroviral vectors for gene therapy applications targeting hematopoietic system was accompanied by instances insertional mutagenesis. These events stimulated ongoing development putatively safer integrating vector systems and analysis methods to characterize compare integration site (IS) biosafety profiles. Continuing advances in next-generation sequencing technologies are driving generation ever-more complex IS datasets. Available bioinformatic tools such datasets focus on association sites (ISs) with selected genomic epigenetic features, choice these features determines ability discriminate between We describe scalable application point-process coherence (CA) patterns produced ISs across intervals, uncoupled from features. To explore CA context an unresolved question, we asked whether differing transduction conditions used initial Paris London SCID-X1 trials result divergent genome-wide tested a carried out under each condition, showed that could indeed resolve differences distributions. Existence confirmed established