Dataset Information

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

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

SUBMITTER: Hallwirth CV

PROVIDER: S-EPMC4445430 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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

Hallwirth Claus V CV Garg Gagan G Peters Timothy J TJ Kramer Belinda A BA Malani Nirav V NV Hyman Jessica J Ruan Xiaoan X Ginn Samantha L SL Hetherington Nicola A NA Veeravalli Lavanya L Shahab Atif A Ranganathan Shoba S Wei Chia-Lin CL Liddle Christopher C Thrasher Adrian J AJ Bushman Frederic D FD Buckley Michael J MJ Alexander Ian E IE

Molecular therapy. Methods & clinical development 20150429

Unequivocal demonstration of the therapeutic utility of γ-retroviral vectors for gene therapy applications targeting the hematopoietic system was accompanied by instances of insertional mutagenesis. These events stimulated the ongoing development of putatively safer integrating vector systems and analysis methods to characterize and compare integration site (IS) biosafety profiles. Continuing advances in next-generation sequencing technologies are driving the generation of ever-more complex IS d ...[more]

PMID: 26029726

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Dataset Information

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

Publications

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

Similar Datasets

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