Scalable and Systematic Neurobiology of Psychiatric and Neurodevelopmental Disorder Risk Genes (SSPsyGene) Consortium: Data Resource and Administrative Coordination Center

Presenter

David Panchision, Ph.D.
Division of Neuroscience and Basic Behavioral Science

Goal

This concept aims to continue the Data Resource and Administrative Coordination Center (DRACC) of the Scalable and Systematic Neurobiology of Psychiatric and Neurodevelopmental Disorder Risk Genes (SSPsyGene) Consortium to support ongoing needs for data production and analysis that will continue beyond the current DRACC project end date and to complete consortium studies.

Rationale

Launched in 2023, the SSPsyGene Consortium’s goal is to systematically study how the large number of risk genes for neurodevelopmental and psychiatric disorders (NPDs) affect molecular, cellular, circuit, and systems/organismal biology. The integration of this phenotypic data into a harmonized, integrated knowledge base will provide a solid foundation to make robust inferences into potential shared and unique disease mechanisms across NPDs. The consortium includes Assay and Data Generation Centers (ADGCs) that carry out high-throughput assays in a variety of model systems, under consortium-wide coordination by the DRACC. Progress thus far includes the generation of human induced pluripotent stem cell lines with loss of function mutations in each of 250 selected risk genes (e.g., for autism, schizophrenia, bipolar disorder) with ongoing characterization of gene expression, developmental trajectories and neuronal activity measures. ADGCs are progressing toward generating 100+ similar mutations in zebrafish and mice and characterizing function through behavior. The DRACC coordinates all activities including gene selection, the establishment of data standards, the ongoing processing and submission of data to The Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative archives, the early stages of joint data analysis, and the establishment of an early knowledge base framework. The phased onset of ADGCs over the course of the SSPsyGene initiative extends these coordination needs beyond the current DRACC project end date.

The DRACC will continue to provide administrative and logistical coordination to the consortium and ensure standardized and consistent harmonized data processing, analysis and archiving pipelines. The DRACC will further refine its focus on developing a sustainable knowledge base, with shared terms, definitions, and data standards that are interoperable with other knowledge platforms and will enable the use of artificial intelligence to accelerate research on brain function and NPDs. Expected outcomes will include high-quality, multi-modal data on risk gene function in a variety of biological contexts, with curated data and knowledge shared as a resource for broad use by the biomedical research community toward understanding the mechanistic basis of NPDs. This concept will continue to advance NIH priorities that foster (1) replication and reproducibility, (2) alternative testing models, and (3) artificial intelligence, in support of (4) furthering our understanding of autism and related NPDs.