An Integrative Connectomics Coordination Center (IC3)

The unique capabilities of mammalian brains arise from their extraordinarily complex network structure, with billions to trillions of synaptic connections among millions to billions of neurons that form thousands of cell types and countless functionally specific circuit pathways. Unraveling this network structure, the connectome, holds the key to understanding how the brain generates behavior, thoughts, emotion and other functions. The newly launched BRAIN Initiative Connectivity Across Scales (BRAIN CONNECTS) program aims to develop cutting- edge, highly scalable technology platforms that enable the generation of unprecedented volumes of data in different and complementary modalities, to create comprehensive brain-wide connectivity maps in mouse, non- human primate (NHP) and human at different resolutions. These connectivity maps will serve as foundational resources to the community to dramatically accelerate and transform our understanding of brain functions and diseases. The Integrative Connectomics Coordination Center (IC3) proposed here will work closely with BRAIN CONNECTS data generation teams to ensure the successful realization of the program goals. The IC3 brings together a team of investigators with extensive experience in various connectomics technologies, large-scale experimental and computational platform development, and consortium management and leadership. We will coordinate the activities of the BRAIN CONNECTS Network across comprehensive centers and specialized technology groups. Collaborating with data generation groups, we will develop and harmonize three of the four common data processing pipelines in the network, including electron microscopy, fluorescence light microscopy, and barcoded sequencing datasets. We will organize and conduct rigorous evaluation of the technologies for improved performance and scalability, to enable the next phase of whole-brain scale data generation. We will develop cloud-based data platforms and analytic tools to facilitate consortium-wide data integration and joint analysis. We will broadly distribute these tools and products for democratized access and analysis by the research community. We will establish a BRAIN CONNECTS Knowledge Base (CONNECTS-KB), along with advanced AI/ML based tools, to incorporate connectivity data into whole brain Common Coordinate Frameworks (CCFs), achieve integration between molecularly defined cell types and connectivity, and create a unified representation of brain connectivity across data modalities and across species. We will facilitate the demonstration of science and health impacts of the BRAIN CONNECTS program to the broad research community and the general public, through proof-of-concept case studies, online tools allowing external researchers to access and use the integrated data and connectivity maps, and public-facing outreach and education activities.