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Abstracts

GRIN Portal: An Interactive Web Application Exploring GRIN Genes and Related Disorders

Abstract number : 1.351
Submission category : 12. Genetics / 12A. Human Studies
Year : 2021
Submission ID : 1826281
Source : www.aesnet.org
Presentation date : 12/4/2021 12:00:00 PM
Published date : Nov 22, 2021, 06:53 AM

Authors :
Chiara Klöckner, cand. med. - Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany; Tobias Brünger - Cologne Center for Genomics (CCG), University of Cologne, Cologne, 50931, Germany; Eduardo Pérez-Palma - Universidad del Desarrollo, Centro de Genética y Genómica, Facultad de Medicina Clínica Alemana. Santiago, Chile; Ilona Krey - Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany; Marie Gramm - Cologne Center for Genomics (CCG), University of Cologne, Cologne, 50931, Germany; Scott Myers - Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA, 30322, USA. Center for Functional Evaluation of Rare Variants (CFERV), Emory University School of Medicine, Atlanta, GA, 30322, USA; Hongjie Yuan - Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA, 30322, USA. Center for Functional Evaluation of Rare Variants (CFERV), Emory University School of Medicine, Atlanta, GA, 30322, USA; Arthur Stefanski - Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Patrick May - Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg; Jenifer Sargent - University of Colorado School of Medicine, Aurora, Colorado, USA; Kristen Park - University of Colorado School of Medicine, Aurora, Colorado, USA; Amy Ramsey - Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Tim Benke - University of Colorado School of Medicine, Aurora, Colorado, USA; Stephen Traynelis - Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA, 30322, USA. Center for Functional Evaluation of Rare Variants (CFERV), Emory University School of Medicine, Atlanta, GA, 30322, USA; Dennis Lal - Cologne Center for Genomics (CCG), University of Cologne, Cologne, 50931, Germany. Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA. Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH 44106, USA. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Johannes Lemke - Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany

Rationale: With the emerging number of individuals diagnosed with GRIN-related disorders, there also comes a need to structure and store disease-related data to facilitate its use in research and clinical practice. Currently, interpreting variants in GRIN1, GRIN2A, GRIN2B, or GRIN2D remains challenging and predicting the clinical outcome is difficult. To advance clinical evaluation and support research on GRIN-related disorders, we developed the GRIN Portal. As an interactive web application, it offers aggregated and harmonized GRIN-related data made accessible researchers, clinicians as well as families.

Methods: For the GRIN Portal, we combine manually curated data from the global GRIN Patient Registry, functional data from the Center for Functional Evaluation of Rare Variants (CFERV, Emory University), and data on animal studies. Annotation, variant mapping, visualization, and application design were developed using the Shiny framework. App deployment, hosting, and updating were performed using Google Cloud services.

Results: By including phenotypic (n = 502 individuals) and functional data (n = 603 variants), as well as extensive bioinformatic analyses and visualizations, the GRIN Portal offers comprehensive information on GRIN variants and disease assessment. The GRIN Portal is structured in five interfaces to appeal to different user interests: a) “Basic Information” focuses on general information on GRIN genes and related disorders by offering summary statistics and literature references. b) “Families” offers educational resources as well as links to organizations. c) “Variant Analysis” facilitates the evaluation of single-nucleotide variants. The user selects a GRIN variant of interest and receives information on location, clinical information, functional consequence, paralogous variants, and comparative information such as on variants located in the same functional domain. It also covers automated ACMG classification, including the ClinGen GRIN Variant Curation Expert Panel specifications. d) “Research” focuses on variants matching aspects of interest specified by the user, e.g. association with specific phenotypes or functional effects. e) “GRIN Registry” describes how to be recruited in the global GRIN Patient Registry to ultimately encourage families and clinicians to support GRIN research.

Conclusions: The GRIN Portal is a comprehensive and interactive web application aiming to expand knowledge on GRIN genes and related disorders. It aggregates and standardizes data from different resources and makes it interactively accessible for different audiences. The website is freely available at grin-portal.broadinstitute.org.

Funding: Please list any funding that was received in support of this abstract.: GRIN2B foundation, CURE foundation, Ponzio Family Chair in Neurology Research/Children’s Hospital Colorado Foundation (TB)
NIH/NINDS (SFT, R35NS111619), NIH/NICHD (HY, R01HD082373), Austin Purpose (SFT), GRIN2B foundation (HY).

Genetics