Data Science Seminars: Bioinformatics focus

Speaker:  Francesco Gazzo

June 9^th, 2026 | 2:15 pm
DEIB, PT2 Meeting Room (Bld. 20A)

For further information please contact:  Silvia Cascianelli |  silvia.cascianelli@polimi.it

Abstract

Tuesday, June 9^th, 2026 at 2:15 pm a new appointment of Data Science Seminars: Bioinformatics focus will take place in DEIB PT2 Meeting Room (Building 20A) organized by the Data Science for Bioinformatics group.

The seminar will be held by Francesco Gazzo, PHD Student in Information Technology, on the following subject: "VISMA: A Computational Workflow to Quantify Somatic Mutagenesis Around Lentiviral Integration Sites at Single-Clone Resolution".

Lentiviral vectors (LVs) enable durable hematopoietic stem cell gene therapy (HSC-GT) by integrating therapeutic cassettes into the host genome. Because integration is semi-random, LV insertions can perturb nearby regulatory elements, and proliferative stress may further contribute to genetic instability, yet quantitative methods to connect clonal expansion with local mutagenesis are limited. We present VISMA (Vector Integration Site Mutation Analysis), a reproducible computational workflow that calls somatic variants in genomic regions flanking each integration site (IS), enabling clone-resolved mutation burden estimates across time and lineages.
VISMA extends VISPA2-derived IS catalogs by preprocessing and artifact reduction (optical-duplicate removal, end trimming), IS-aware read assignment and aggregation across samples, SNV/indel calling with temporal “backtracing” to reconstruct occurrence and variant allele frequency, and stringent filtering to remove likely germline events and sequence-context artifacts. For downstream quantification, VISMA computes a covered bases normalized Mutation Rate and introduces a Mutation Index that additionally normalizes across the number of IS and overall clonal representation, yielding an interpretable global metric.
We applied VISMA to a longitudinal mouse HSC-GT model (WT vs Cdkn2a-/-) using either a genotoxic LV or a GT-like non-genotoxic LV. Across >200,000 unique IS and >9 Gb of flanking sequence, VISMA detected a significantly increased mutation burden in genotoxic LV groups, with the strongest effect in Cdkn2a-/- + genotoxic LV, consistent with synergy between vector genotoxicity and impaired oncogene surveillance. Whole-genome sequencing supported higher mutagenesis in genotoxic conditions, corroborating VISMA’s flanking-region analysis. VISMA provides a practical computational framework for assessing vector-associated mutagenesis and genotoxic risk in HSC gene therapy. Moreover, we are now testing the workflow on our gene therapy patients, with promising results.