Bioinformatic clonality analysis of next-generation sequencing-derived viral vector integration sites.

Human Gene Therapy Methods
Anne ArensManfred Schmidt

Abstract

Clonality analysis of viral vector-transduced cell populations represents a convincing approach to dissect the physiology of tissue and organ regeneration, to monitor the fate of individual gene-corrected cells in vivo, and to assess vector biosafety. With the decoding of mammalian genomes and the introduction of next-generation sequencing technologies, the demand for automated bioinformatic analysis tools that can rapidly process and annotate vector integration sites is rising. Here, we provide a publicly accessible, graphical user interface-guided automated bioinformatic high-throughput integration site analysis pipeline. Its performance and key features are illustrated on pyrosequenced linear amplification-mediated PCR products derived from one patient previously enrolled in the first lentiviral vector clinical gene therapy study. Analysis includes trimming of vector genome junctions, alignment of genomic sequence fragments to the host genome for the identification of integration sites, and the annotation of nearby genomic elements. Most importantly, clinically relevant features comprise the determination of identical integration sites with respect to different time points or cell lineages, as well as the retrieval of the mo...Continue Reading

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Citations

Oct 4, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kaifeng ShaoWolfgang Wagner
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Apr 30, 2020·Molecular Therapy. Methods & Clinical Development·Saira AfzalManfred Schmidt

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Methods Mentioned

BETA
dissection
PCR
restriction digest

Software Mentioned

Excel
Google Web Toolkit ( GWT
sfffinfo
Spreadsheet
sfffile
HISAP
- WriteExcel
- ParseExcel
BLAST BLAT
Perl

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