g-TRIS

g-TRIS implements a graph-based, genome-free alignment algorithm to identify and map vector genomic insertion sites in host genomes, including insertions embedded in low complexity and repetitive regions, and to retrieve sequences flanking virus-host DNA junctions for improved clonal quantification and tracking in gene therapy and viral infection studies.

Key Features:

• Graph-based genome-free alignment: Uses a graph-based, genome-free alignment approach to assign and compare insertion-associated sequences without relying on a reference genome.
• Insertion site identification and mapping: Identifies and maps vector genomic insertion sites within host genomes.
• Low complexity and repetitive-region detection: Detects insertions embedded in low complexity or repetitive regions, addressing approximately 30% of insertions that occur in these challenging genomic areas.
• Flanking sequence retrieval and mapping: Retrieves and maps sequences flanking virus-host DNA junctions to improve junction assignment and site localization.
• Novel algorithmic framework: Implements a novel algorithmic framework to enhance the retrieval and mapping of virus-host junction sequences.
• Improved clonal quantification and tracking: Yields improved clonal quantification and tracking accuracy in clinical reanalysis datasets.

Scientific Applications:

• Gene therapy integration analysis: Mapping and monitoring of vector integration sites to track the evolution of genetically modified cells in vivo in gene therapy contexts.
• Viral insertion studies: Identification of viral genomic insertion sites in studies involving virally infected patients.
• Clonal tracking and quantification: Quantification and longitudinal tracking of clones based on insertion site profiles.
• Analysis of repetitive genomic regions: Investigation of insertion events occurring within low complexity and repetitive regions of the genome.

Methodology:

Computational methods include a graph-based, genome-free alignment algorithm and an algorithmic framework for retrieval and mapping of sequences flanking virus-host DNA junctions.