NDD-CNV Portal: Facilitating Genetic Test Interpretation, Research and Education for Neurodevelopmental CNVs
Abstract number :
1.342
Submission category :
12. Genetics / 12A. Human Studies
Year :
2021
Submission ID :
1826197
Source :
www.aesnet.org
Presentation date :
12/4/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:52 AM
Authors :
Marie Macnee, M.Sc. - Medical Faculty of the University of Cologne, University Hospital of Cologne; Eduardo Pérez-Palma - Universidad del Desarrollo, Centro de Genética y Genómica, Facultad de Medicina Clínica Alemana. Santiago, Chile; Tobias Brünger - Cologne Center for Genomics (CCG), Medical Faculty of the University of Cologne, University Hospital of Cologne, Cologne, Germany; Chiara Klöckner - Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany; Arthur Stefanski - Genomic Medicine Institute & Epilepsy Center, Cleveland Clinic, Cleveland, OH; Patrick May - Bioinformatics Core, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 4362, Esch-sur-Alzette, Luxembourg; Johannes Lemke - Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany; Bina Shah - Project 8p Foundation, New York, New York, USA; Yssa DeWoody - Ring14 USA and Ring14 International, Midland, Texas, USA; Vanessa Vogel-Farley - Dup15q Alliance, Highland Park, Illinois, USA; Glennis Logsdon - Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA; Evan Eichler - Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA; Dennis Lal - Genomic Medicine Institute & Epilepsy Center, Cleveland Clinic, Cleveland, OH. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; . Commission On Novel Technologies For Neurodevelopmental CNVs - .
Rationale: Copy number variants (CNVs) can cause a spectrum of neuropsychiatric and neurodevelopmental disorders (NDDs). However, variant interpretation, including phenotype driver and modifier gene identification, still represent a challenge, even for experts. Currently, clinical, genetic, and molecular data about CNVs are not connected and distributed across registries, databases, and the literature. To overcome current limitations, we are developing the NDD-CNV Portal, an interactive website that displays expert-curated CNV datasets alongside biomedical annotations, user-friendly analytics, and educational resources.
Methods: In this ongoing project, we aggregated clinical, genomic, transcriptomic and proteomic data from 30 patients with pathogenic 8p (n=10), Ring14 (n=5), and Dup15 (n=15) CNVs from patient collaboratives. In addition, we collected and curated additional pathogenic and population CNVs from databases such as the UK-Biobank, gnomAD, ClinVar, and DECIPHER. To enable exploration of CNVs, we developed interfaces that visualize overlap of patient CNVs with population CNVs, genomic regulatory elements, disease-associated genes, SNVs, GWAS hits and >20 gene-level features such as (inter-and intraspecies) sequence constraint metric, dosage sensitivity, tissue, and cell-type level expression. By combining gene-level features, we rank genes in the order of most likely responsible genes and provide enrichment analyses of phenotype, functional, and pathway annotations. In addition to the search based on genomic position, the user can also perform disorder-specific and across-disorder genotype-phenotype analyses.
Results: We designed the NDD-CNV Portal for three user scenarios: i) Education of NDD-CNV-related diseases, ii) Expert-level variant interpretation using CNV guideline-based variant pathogenicity classification tools, and iii) Research using interactive tools and visualizations to explore the rich source of interconnected data and annotations.
Conclusions: The NDD-CNV Portal infrastructure is scalable and will integrate novel data types. As such, it has the potential to transform variant interpretation, research, and education for neurodevelopmental CNV-associated disorders. We are actively looking for collaborators contributing to this project.
Funding: Please list any funding that was received in support of this abstract.: -
Genetics