VISA - Vector Integration Site Analysis server: a web-based server to rapidly identify retroviral integration sites from next-generation sequencing

BackgroundAnalyzing the integration profile of retroviral vectors is a vital step in determining their potential genotoxic effects and developing safer vectors for therapeutic use. Identifying retroviral vector integration sites is also important for retroviral mutagenesis screens.ResultsWe developed VISA, a vector integration site analysis server, to analyze next-generation sequencing data for retroviral vector integration sites. Sequence reads that contain a provirus are mapped to the human genome, sequence reads that cannot be localized to a unique location in the genome are filtered out, and then unique retroviral vector integration sites are determined based on the alignment scores of the remaining sequence reads.ConclusionsVISA offers a simple web interface to upload sequence files and results are returned in a concise tabular format to allow rapid analysis of retroviral vector integration sites.

[1]  John J. Rossi,et al.  Foamy Combinatorial Anti-HIV Vectors with MGMTP140K Potently Inhibit HIV-1 and SHIV Replication and Mediate Selection In Vivo , 2009, Gene Therapy.

[2]  Sean D. Mooney,et al.  Identifying viral integration sites using SeqMap 2.0 , 2011, Bioinform..

[3]  H. Kiem,et al.  High-throughput genomic mapping of vector integration sites in gene therapy studies. , 2014, Methods in molecular biology.

[4]  Hans-Peter Kiem,et al.  Foamy virus vector integration sites in normal human cells , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Daniel G. Miller,et al.  Comparison of HIV-derived lentiviral and MLV-based gammaretroviral vector integration sites in primate repopulating cells. , 2007, Molecular therapy : the journal of the American Society of Gene Therapy.

[6]  Christof von Kalle,et al.  Bioinformatic clonality analysis of next-generation sequencing-derived viral vector integration sites. , 2012, Human gene therapy methods.

[7]  Cameron S. Osborne,et al.  LMO2-Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1 , 2003, Science.

[8]  A. Nalla,et al.  A novel approach to identify driver genes involved in androgen-independent prostate cancer , 2014, Molecular Cancer.

[9]  D. Rawlings,et al.  Foamy viral vector integration sites in SCID-repopulating cells after MGMTP140K-mediated in vivo selection , 2015, Gene Therapy.

[10]  Paul Shinn,et al.  HIV-1 Integration in the Human Genome Favors Active Genes and Local Hotspots , 2002, Cell.

[11]  Zhongming Zhao,et al.  VirusFinder: Software for Efficient and Accurate Detection of Viruses and Their Integration Sites in Host Genomes through Next Generation Sequencing Data , 2013, PloS one.

[12]  Gianluigi Zanetti,et al.  VISPA: a computational pipeline for the identification and analysis of genomic vector integration sites , 2014, Genome Medicine.

[13]  Christine Kinnon,et al.  Mutations in TNFRSF13B Encoding TACI Are Associated With Common Variable Immunodeficiency in Humans , 2006, Pediatrics.

[14]  G. Trobridge Genotoxicity of retroviral hematopoietic stem cell gene therapy , 2011, Expert opinion on biological therapy.

[15]  W. J. Kent,et al.  BLAT--the BLAST-like alignment tool. , 2002, Genome research.