Isling: A Tool for Detecting Integration of Wild-Type Viruses and Clinical Vectors. Issue 11 (15th June 2022)

• Record Type: Journal Article
• Authors: Scott, Suzanne; Hallwirth, Claus V.; Hartkopf, Felix; Grigson, Susanna; Jain, Yatish; Alexander, Ian E.; Bauer, Denis C.; Wilson, Laurence O.W.
• Is Part Of: Journal of molecular biology. Volume 434:Issue 11(2022)
• Publication Date: 2022-06-15
• Subjects: virology -- gene therapy -- bioinformatics -- genotoxicity -- cancer; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2021.167408
• Languages: English
• ISSNs: 0022-2836

Abstract

Graphical abstract: Highlights: Detecting integrations of viral and vector genomes is critical in many fields. Isling is the first tool identifying integrations of both virus and vector genomes. Isling up to 170% more accurate and 1.6-fold faster than other software. Isling enables comparisons of wild-type virus and gene therapy vector integrations. Abstract: Detecting viral and vector integration events is a key step when investigating interactions between viral and host genomes. This is relevant in several fields, including virology, cancer research and gene therapy. For example, investigating integrations of wild-type viruses such as human papillomavirus and hepatitis B virus has proven to be crucial for understanding the role of these integrations in cancer. Furthermore, identifying the extent of vector integration is vital for determining the potential for genotoxicity in gene therapies. To address these questions, we developed isling, the first tool specifically designed for identifying viral integrations in both wild-type and vector from next-generation sequencing data. Isling addresses complexities in integration behaviour including integration of fragmented genomes and integration junctions with ambiguous locations in a host or vector genome, and can also flag possible vector recombinations. We show that isling is up to 1.6-fold faster and up to 170% more accurate than other viral integration tools, and performs well on both simulated and real datasets. Isling is therefore an efficient and application-agnostic tool that will enable a broad range of investigations into viral and vector integration. These include comparisons between integrations of wild-type viruses and gene therapy vectors, as well as assessing the genotoxicity of vectors and understanding the role of viruses in cancer.