INSPIIRED

INSPIIRED analyzes viral integration sites in cellular genomes to map integration loci, quantify clonal expansion, and support safety and efficacy assessment in human gene therapy studies.

Key Features:

• Data input and analysis: Processes integration site data generated through the INSPIIRED pipeline using paired-end sequencing to map integration sites and infer numbers of transduced cells.
• Visualization tools: Produces interactive heatmaps for comparing integration site distributions against genomic features and supports user-defined statistical tests for quantitative comparisons.
• Reproducible reporting: Generates standardized reports summarizing sample population structure, longitudinal dynamics, and frequencies of integrations near cancer-associated genes in human gene therapy samples.
• UC50 statistic: Calculates the UC50 metric to quantify clonal expansion by summarizing the contribution of unique progenitors to the most expanded 50% of progeny clones.

Scientific Applications:

• Longitudinal monitoring in clinical trials: Supports long-term analysis of integration site dynamics in patients, exemplified by studies of severe combined immunodeficiency-X1 (SCID-X1) gene therapy cohorts.
• Immune reconstitution assessment: Enables evaluation of immune system reconstitution over extended periods through tracking of integration site–defined clones.
• Safety surveillance: Facilitates detection and characterization of persistent clones with integrations near cancer-associated genes, including identification of an integration site near CCND2.

Methodology:

Processes INSPIIRED pipeline integration site data using paired-end sequencing to map viral integrations and infer transduced cell numbers; computes the UC50 statistic; applies user-defined statistical tests and produces interactive heatmaps and standardized reports.