GMKF competing renewal

/Abstract We propose to continue to provide data generation and processing activities that will enrich a genomic data resource to propel pediatric disease research with this supplement proposal. Key elements for success will be the provision of high quality genome sequence data on well- phenotyped patients and their families; the collection and accessibility of data to the research community in an intuitive manner; and the integration of genetic data with phenotypic information in the context of this program and comparison to other large data resources. Our center brings the domain expertise in high throughput data generation, processing and analysis, and disease gene discovery required to meet the objectives of the Kids First program. We will apply deep, high-quality whole genome sequencing and RNA sequencing data, among other data types) on samples to be provided by investigators. We will be flexible to work closely and accommodate the needs and interests of selected X01 Investigators. We will participate in the evaluation of these data types and their overall impact on discovery and scientific output of the program. A key feature of our center is our implementation of a robust analytical framework for variant assessment and disease gene discovery, which builds on Broad investigators' world- leading roles in statistical genetics, functional annotation, and clinical variant interpretation as well as access to exome and genome data from hundreds of thousands of samples sequenced at Broad. This has enabled us to build a systematic pipeline for gene discovery that will be made freely available to the program. With data produced and processed in a consistent way, we can offer seamless integration of data into our analytic framework. For many of the co- morbidities targeted by the research community, confident discovery of causal genes will require aggregation of cases across centers around the world. We will partner with the Data Coordinating Center to enable the project to make the data available to investigators. With this, we hope to support the Kids First research program as a whole and establish standards for data sharing in clinical genomics, accelerating collaboration and facilitating robust gene discovery. Project Number: 3U24HD090743-09S1 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Stacey Gabriel | Institution: BROAD INSTITUTE, INC., CAMBRIDGE, MA | Award Amount: $5,112,625 | Activity Code: U24 View on NIH RePORTER: https://reporter.nih.gov/project-details/3U24HD09074309S1