Poster #17: Patrick Van Hoose PhD

The Developmental Genotype Expression Project metadata framework creates the foundation for advancements in pediatric research

Patrick Van Hoose, PhD (National Disease Research Interchange), Raquel G. Hernandez, MD, MPH, FAAP (Johns Hopkins All Children’s Hospital), Melissa Faith, PhD (Johns Hopkins All Children’s Hospital), Simone Guambana, MS (Johns Hopkins All Children’s Hospital), Thomas G. Blanchard, PhD, JD (University of Maryland School of Medicine), Deanne M. Taylor, PhD (Children’s Hospital of Philadelphia), Rebecca L. Linn, MD (Children’s Hospital of Philadelphia), Meghan Delaney, MD (Children’s National Hospital), Daniel G. Leino, MD (Cincinnati Children’s Hospital), Melissa W. VonDran, PhD (National Disease Research Interchange) and Thomas J. Bell, MS, PhD (National Disease Research Interchange)

The Developmental Genotype Tissue Expression (dGTEx) project is a large-scale initiative to address a significant gap in our understanding of how gene expression is regulated during development. The dGTEx project has three primary goals: 1) to create an atlas of gene expression in pediatric tissues, 2) evaluate gene expression during development and 3) create a resource of pediatric tissue and genetic data. As a first-of-its kind resource for the pediatric research community, the program developed tissue and data collection methods to maximize donated gifts from eligible pediatric donors. Methods: The dGTEx Biospecimen Procurement Center (BPC) is a multi-institutional effort collaborating with a select number of organ procurement organizations (OPOs) to collect biospecimens from 120 pediatric donors. OPOs utilize project-specific donor screening tools, authorization for donation, donor questionnaires, and standardized recovery protocols to collect up to 40 tissue types from each donor. The dGTEx BPC is responsible for processing, pathology of tissues post-recovery and metadata collection. An integrated ethical, legal, and social implications (ELSI) study team provides ongoing assessment of donor family needs as well as engagement with community stakeholders. Results: A total of ~274 metadata fields are collected per donor including age, detailed tissue pathological evaluations, tissue recovery details, death circumstances, past medical history, and pubertal status. Pathological evaluation of recovered tissues was expanded beyond traditional tissue quality control to describe autolysis, cellular composition and maturation assessment of tissue samples to allow greater insight for molecular data analysis. The BPC constructed a unified Uberon-based tissue categorization that harmonizes terminology from multiple sources into a single, coherent framework across all dGTEx tissues. An integrated, harmonized approach including donor-level metadata, sample-level attributes, and digital pathology produced a fully aligned tissue annotation framework that spans all donors, all samples, and associated pathology assessments within dGTEx. The extensive metadata collection and framework for dGTEx will enhance developmental comparisons, guide experimental analysis, and strengthen the dGTEx resource for the scientific and medical communities.