- Integrating structural variant calling, annotation and prioritization into whole genome analysis workflows: a practical application in the molecular diagnosis of neurodevelopmental disorders
- Iovino, Emanuela <1987>
Subject
- MED/03 Genetica medica
Description
- Background: WGS is increasingly used as a first-line diagnostic test for patients with rare genetic diseases such as neurodevelopmental disorders (NDD). Clinical applications require a robust infrastructure to support processing, storage and analysis of WGS data. The identification and interpretation of SVs from WGS data also needs to be improved. Finally, there is a need for a prioritization system that enables downstream clinical analysis and facilitates data interpretation. Here, we present the results of a clinical application of WGS in a cohort of patients with NDD. Methods: We developed highly portable workflows for processing WGS data, including alignment, quality control, and variant calling of SNVs and SVs. A benchmark analysis of state-of-the-art SV detection tools was performed to select the most accurate combination for SV calling. A gene-based prioritization system was also implemented to support variant interpretation. Results: Using a benchmark analysis, we selected the most accurate combination of tools to improve SV detection from WGS data and build a dedicated pipeline. Our workflows were used to process WGS data from 77 NDD patient-parent families. The prioritization system supported downstream analysis and enabled molecular diagnosis in 32% of patients, 25% of which were SVs and suggested a potential diagnosis in 20% of patients, requiring further investigation to achieve diagnostic certainty. Conclusion: Our data suggest that the integration of SNVs and SVs is a main factor that increases diagnostic yield by WGS and show that the adoption of a dedicated pipeline improves the process of variant detection and interpretation.
Date
- 2023-06-16
- info:eu-repo/date/embargoEnd/2025-06-15
Type
- Doctoral Thesis
- PeerReviewed
Format
- application/pdf
Identifier
urn:nbn:it:unibo-29470
Iovino, Emanuela (2023) Integrating structural variant calling, annotation and prioritization into whole genome analysis workflows: a practical application in the molecular diagnosis of neurodevelopmental disorders, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Data science and computation