Key Dates

NOT-MH-21-260- Notice of Intent to Publish a Funding Opportunity Announcement for BRAIN Initiative Cell Atlas Network (BICAN): Comprehensive Center on Human and Non-human Primate Brain Cell Atlases (UM1 Clinical Trial Not Allowed);

NOT-MH-21-261- Notice of Intent to Publish a Funding Opportunity Announcement for BRAIN Initiative Cell Atlas Network (BICAN): Specialized Collaboratory on Human, Non-human Primate, and Mouse Brain Cell Atlases (U01 Clinical Trial Not Allowed);

National Institute of Mental Health (NIMH)

National Eye Institute (NEI)

National Institute on Aging (NIA)

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

National Institute of Biomedical Imaging and Bioengineering (NIBIB)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

National Institute on Deafness and Other Communication Disorders (NIDCD)

National Institute on Drug Abuse (NIDA)

National Institute of Neurological Disorders and Stroke (NINDS)

National Center for Complementary and Integrative Health (NCCIH)

The National Institute of Mental Health (NIMH), along with the NIH Institutes and Centers participating in the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, intends to issue a Funding Opportunity Announcement (FOA) to support an integrated Coordinating Unit of Biostatistics, Informatics, and Engagement (CUBIE) that will be composed of four subunits to establish respectively (1) a common sequencing data processing pipeline, (2) a common imaging data processing pipeline, (3) a comprehensive brain cell knowledge base, and (4) an engagement and outreach element to coordinate the research activities within and beyond the BICAN. CUBIE is expected to coordinate and collaborate with BICAN and other interested investigators in the research community to build reference brain cell atlases that will be widely used throughout the research community, providing a molecular and anatomical foundational framework for the study of brain function and disorders. In particular, CUBIE is expected to interact closely with the BRAIN Initiative data archives in building the common data processing pipelines upon cloud-based infrastructure with high-performance computing environment. Applications are expected to propose only one of the above four respective subunits.

This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects.

The FOA is expected to be published in July, 2021 with an expected application due date in November, 2021.

This FOA will utilize the U24 activity code. Details of the planned FOA are provided below.

Background

This FOA is related to the recommendations by the Advisory Committees to the NIH Director as described in Priority Area 1. Discovering Diversity and Priority Area 2. Maps at Multiple Scales in BRAIN 2025 Report, and the transformative project, The Human Brain Cell Atlas, in The BRAIN Initiative 2.0: From Cells to Circuits, Toward Cures.

The BRAIN 2025 Report envisioned a systematic census of neuronal and glial cell types in multiple mammalian species. The NIH BRAIN Initiative has implemented this vision by successfully completing a 3-year pilot phase (2014-2017), followed by launching a 5-year phase 2 (2017-2022) BRAIN Initiative Cell Census Network (BICCN) with an emphasis on mouse brain. The BICCN has applied a set of leading-edge single-cell approaches to characterizing molecular signatures, anatomical phenotypes, and functional properties of brain cell types, and rapidly disseminated the cell census data to the public. The BICCN is on track to complete a comprehensive cell census spanning the entire adult mouse brain, as well as to set stage for large-scale cell atlas research in human and NHP brains. Advances in single-cell transcriptomic and epigenomic profiling, anatomical mapping at cellular resolution, and other approaches have proven to be powerful and scalable. In recognition of these advances and the opportunities they enable, the BRAIN Initiative has recently issued a Notice to increase the funding and number of awards available for RFA-MH-21-140, "BRAIN Initiative Cell Census Network (BICCN) Scalable Technologies and Tools for Brain Cell Census; together these events help set the stage toward creating the Human Brain Cell Atlas. At this time, the BRAIN initiative cell census program is looking to establish the BICAN to broaden and deepen the systematic cell census and atlas efforts with a new emphasis on human brain.

The BICAN will be made up of five highly interactive components with complementary roles as follows:

1. Comprehensive Centers on Human and Non-human Primate Brain Cell Atlases (UM1) (Companion, see NOT-MH-21-260)

2. Specialized Collaboratories on Human, Non-human Primate, and Mouse Brain Cell Atlases (U01) (Companion, see NOT-MH-21-261)

3. Coordinating Unit for Biostatistics, Informatics, and Engagement (CUBIE) (U24) (NOT-MH-21-262)

4. BRAIN Initiative Data Archives (R24) (RFA-MH-20-600)

5. Scalable Technologies and Tools Projects (R01) (RFA-MH-21-140)

Research Objectives

CUBIE will serve as a core of the BICAN to coordinate and collaborate with all projects within the Network as well as the broad research community to establish a cell atlas data ecosystem allowing analysis and integration of a variety of brain cell phenotypes and features. The data processing tools and models are expected to be optimized and implementable in the cloud computing environment where the investigators can collaboratively optimize chain of tools and create data sandboxes for testing and comparing their codes and analysis results. CUBIE will be composed of the following four distinct elements. Applicants to this FOA are expected to have the respective computational and biological competencies in the corresponding areas:

1. Common sequencing data processing pipeline. The goal is to establish a common cloud-based platform for analysis, visualization, integration, and query of sequencing data-based molecular signatures of brain cells in human, NHPs, and mouse. Expected sequencing data include single-cell, single-nucleus, and bulk transcriptomics (e.g.,10X Genomics, SMART-seq, sci-RNA-seq, etc.); single-cell, single-nucleus, and bulk epigenomics (e.g., ATAC-seq, mC-seq, HiC, etc.); multi-omics; spatial transcriptomics (e.g., Slide-seq, etc.); whole genome sequence (see BICCN data examples, https://biccn.org/data).

2. Common imaging data processing pipeline. The goal is to establish a common cloud-based platform for registration of images to Common Coordinate Frameworks, analysis, visualization, and query of imaging-based molecular and anatomical phenotypes and features. Expected imaging data include those acquired from multiscale whole brain imaging in human, NHPs, and mouse at cellular resolution, 3D and 2D, immunohistochemistry, cytoarchitecture histology (e.g., Nissl, H&E, myelin, nuclei, mitochondria, etc.), spatial transcriptomics (e.g., MERFISH, etc.), single neuron morphology (fMOST, MouseLight, etc.), neural circuit tracing, etc. Imaging modalities include fluorescence, bright-field, MRI, etc. (see BICCN data examples, https://biccn.org/data).

3. Comprehensive brain cell knowledge base. The goal is to establish a comprehensive brain cell knowledge base that includes data-driven brain cell taxonomies and ontology, and literature reference to link vast data, information, and resources across data modalities, developmental stages, and species.

4. Engagement and outreach. The goal is to coordinate and harmonize data and metadata across the BICAN; facilitate data and metadata submission and public release; track data flow and provenance and data use statistics; collect data users experience within and outside BICAN; establish a BICAN web portal for easy access and query of brain cell atlas data, resource, and knowledge; and organize meetings, working groups, and outreach activities.

An application to this FOA may propose only one of the above components. However, applicants may describe and propose how cross-component collaboration and analysis have been and can be established when appropriate and feasible.

The aggregated capabilities of the awardees from this FOA will produce an ensemble of data analysis tools required to interpret the diverse data types generated by the BICAN. The CUBIE awardees are expected to work closely and collaboratively with all other BICAN projects, and be integrated in the relevant joint analysis working groups that will be formed by BICAN. As a whole, CUBIE will work together to:

• enable the exploration of large-scale brain cell atlas data and knowledge, and inspire research in brain function and disorders;
• ensure research rigor and data reproducibility by making the data to be findable, accessible, interoperable, and reusable, and the process transparent.

Applications are not being solicited at this time.

Please direct all inquiries to:

Yong Yao, Ph.D.
National Institute of Mental Health (NIMH)
301-443-6102
yyao@mail.nih.gov