Congenital Heart Defect-Bio Specimen Resources Core (CHD-BioCore)
Availability and quality of heart tissue from pediatric patients with CHDs with well-defined phenotypes is the rate- limiting factor in any effort to achieve clinically relevant scientific discoveries in the CHD field. Hence, establishing a CHD-BioCore is an essential infrastructure to accelerate scientific discovery and clinical translation by synergizing expertise from a collaborative team from different departments with combined clinical and research expertise. The Core also serves to interact with other CHD network member institutes nationwide and with the Pediatric Cardiac Genomics Consortium.
The CHD-BioCore consists of three central and complementary components:
- CHD Clinical Data Registry
- CHD Bio Banking Repository
- CHD Genomic Data Depository.
1. CHD Clinical Data Registry: Defining CHDs cohort and clinical pool is the first priority to achieve a comprehensive delineation of CHD phenotypes. The enrollment process is simple and cost free. Open eligibility criteria is being utilized to achieve large-scale CHD population without any restriction on ethnic backgrounds, sex or age. All efforts are being made to identify familial cases and enroll other affected siblings and extended family members. Printed materials are regularly utilized to facilitate recruitment. Clinical histories are collected through subject and family interviews in conjunction with retrieving medical record information including hospital course, surgical procedures and medical interventions. The data for every patient is coded individually before storage in structured electronic forms in the CHD clinical data registry. The study code allows linking the data to the corresponding subject within the CHD-BioCore Cohort. The clinical registry data is re-evaluated periodically in view of the newly acquired research discoveries to explore potentials for translation and to improve outcomes.
2. CHD Bio Banking Repository: Proper collection, coding, and bio banking of the biological specimens is imperative to achieve precise molecular and cellular signature. Proper procurement of remnant human tissue samples provides critical resources for gene discovery and translational research. Rapid and coordinated processing and storage of biological specimens allows to present a snapshot of protein and gene expression, genetic and epigenetic alterations, protein and enzyme activity, and/or cellular and tissue architecture through collecting:
- Specimens from cardiac tissue to perform molecular cellular phenotyping, transcriptomic and proteomic studies.
- Blood samples from index subjects and from parents and affected family members to obtain genomic DNA for molecular genetics and genomic studies including whole exome/genome sequencing.
- Blood samples collected from index cases and parents to generate human iPSCs for mechanistic studies, in collaboration with Dr. Joseph Wu Laboratory at the Stanford Cardiovascular Insitute.
3. CHD Genomic Data Depository: Achieving molecular characterization of CHD genotype is essential to study CHDs mechanism. The CHD genomic data depositary is an essential component to build and enrich the CHD-BioCore. The genomic datasets generated from sequencing and omics studies on CHD cohort, when available, are currently deposited in the CHD Genomic Data Depository to facilitate comparative analysis, network construction and gene discovery. As the path towards understanding CHDs progresses, knowledge sharing through informatics databases will accelerate the dissemination and validation of experimental findings.