Slots: 1
Deadlines
Internal Deadline: Wednesday, November 20th, 2024, 5pm PT Contact RII.
LOI: N/A
External Deadline: December 12, 2024
Award Information
Award Type: Cooperative Agreement
Estimated Number of Awards: 1
Anticipated Award Amount: $6,000,000
Who May Serve as PI: Standard NIH requirements.
Link to Award: https://grants.nih.gov/grants/guide/rfa-files/RFA-OD-25-002.html
Process for Limited Submissions
PIs must submit their application as a Limited Submission through the Research Initiatives and Infrastructure (RII) Application Portal: https://rii.usc.edu/oor-portal/. Use the template provided here: RII Limited Submission Applicant Template
Materials to submit include:
- (1) Two-Page Proposal Summary (1” margins; single-spaced; standard font type, e.g. Arial, Helvetica, Times New Roman, or Georgia typeface; font size: 11 pt). Page limit includes references and illustrations. Pages that exceed the 2-page limit will be excluded from review. You must use the template linked above.
- (2) CV – (5 pages maximum)
Note: The portal requires information about the PIs in addition to department and contact information, including the 10-digit USC ID#. Please have this material prepared before beginning this application.
Purpose
Background:
Down syndrome (DS) is the most common genetic cause of intellectual disability, the most common autosomal trisomy, and one of the most visible and universally recognized genetic syndromes. Each year there are approximately 5300 babies born in the United States with Down syndrome. Within the past 25 years, the average lifespan for a person with Down syndrome has doubled, from 30 to 60 years. Despite this increase in lifespan, individuals with Down syndrome and their families face significant health challenges with age, and they have often been excluded from participation in research that could improve their health outcomes and quality of life. While all people with Down syndrome are connected by the common feature of a complete or partial copy of chromosome 21 (trisomy 21), there are significant physical and cognitive differences among them, indicating that inter-individual variability exists.
Down syndrome is associated with an increased prevalence of autism and epilepsy. About 75% of individuals experience cognitive decline in a syndrome that resembles Alzheimer’s disease but has its onset a decade or two earlier than typical Alzheimer’s disease. Individuals with Down syndrome also have high rates of hearing loss, eye abnormalities, congenital heart defects, sleep apnea, pulmonary hypertension, gastrointestinal malformations, thyroid disease, leukemia, and other autoimmune or immune dysregulation disorders including celiac disease. However, people with Down syndrome infrequently develop solid tumors such as breast or prostate cancer, and despite multiple risk factors for coronary artery disease and high rates of obesity, sleep apnea, and type 1 diabetes, they rarely develop atherosclerosis or have myocardial infarctions. Understanding this unique combination of risks and resiliencies will inform medical advances for individuals with Down syndrome, and for individuals who do not have Down syndrome but share these co-occurring conditions.
This limited competition Notice of Funding Opportunity (NOFO) is one of several NIH-wide research initiatives created in response to Fiscal Years 2018-2024 Omnibus Appropriations Reports, which encourage NIH to expand its current efforts on Down syndrome and common co-occurring conditions also seen in the general population, while increasing the number of Down syndrome investigators and the diversity of study populations and researchers. Together, the initiatives are called the INCLUDE Project (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE). Information about projects that were funded in prior years, as well as the NIH INCLUDE Down Syndrome Research Plan, are available on the INCLUDE Project website at https://www.nih.gov/include-project/. The INCLUDE Project has three components:
- Component 1: Targeted high risk – high reward basic science studies in areas highly relevant to Down syndrome
- Component 2: Assembly of a large cohort of individuals with Down syndrome across the lifespan to perform deep phenotyping and study co-existing conditions
- Component 3: Inclusive clinical trials of existing and future treatments and interventions for co-occurring conditions in individuals with Down syndrome.
This research initiative expands many of the research objectives and opportunities previously highlighted in the 2014 Down Syndrome Directions: NIH Research Plan on Down Syndrome. More recent discoveries have enhanced our understanding of chromosome segregation and chromosome silencing, identified certain proteins and neurotropic factors involved in brain development using mouse models, and uncovered the role of interferons in immune dysregulation, each of which have the potential to lead to development of novel therapies for individuals with Down syndrome, as well as broader applications. People with Down syndrome are often excluded from clinical research, such as trials of potentially beneficial drugs and therapeutics that are used to treat the same condition in the general population. There is great value in connecting people with Down syndrome to therapies that could improve their overall health and quality of life. And there is great interest in the Down syndrome community in participating in clinical research, based on experience from NICHD’s “DS-Connect®: The Down Syndrome Registry®,” an online survey tool that connects individuals with Down syndrome and their families to research opportunities. A comprehensive clinical cohort study with deep phenotyping and exploration of pan-omics will permit identification of biomarkers and outcomes for the co-occurring conditions in Down syndrome. Coupled with development of a clinical trials readiness program, and informed by basic science discoveries, this combination of resources could have a great impact on addressing health disparities that exist for people with Down syndrome and could also lead to the development of therapies to improve outcomes for those with and without the condition. For a list of projects funded from FY2018 to 2023, see https://www.nih.gov/include-project/funding.
This RFA addresses Component 2 of the INCLUDE Project to continually develop the INCLUDE Data Coordinating Center (DCC). The mission of the INCLUDE DCC is to accelerate discoveries that continuously improve and enrich the lives of people with Down syndrome through accessible data resources that enable interdisciplinary collaboration, connected communities, and the expansion of a global Down syndrome knowledge ecosystem. Under the first funding round, the INCLUDE DCC successfully launched the INLCUDE Data Hub on March 21, 2021. The INCLUDE Data Hub is not only a secure data repository for de-identified participant’s data, but also comprises a data portal and a cloud-based platform, Cavatica, for secure cloud computing.
Scope:
The recipient funded by this NOFO will continue their effort on three broad responsibilities: constructing a Data Hub Core, formerly the Data Portal Core, charged with integrating and sharing INCLUDE Project data through the INCLUDE Data Hub which includes a web-based data portal, data repository services, integrated cloud analysis platform(s), and associated infrastructure, serving as a Data Management Core (DMC) and developing and managing an Administrative and Outreach Core (AOC) for the entire DCC. The INCLUDE Data Hub serves as the primary data repository for INCLUDE Project data and provides tools to facilitate access and analyses by the broader research community. The DMC coordinates the collection of data from researchers and data generators and aggregates and harmonizes these data to be shared through the Data Hub. The AOC coordinates administrative logistics as well as training sessions and education on using the Data Hub and works closely with the Steering Committee (see below under Cooperative Agreement Terms and Conditions of Award for a description of the steering committee) on overall implementation of the program goals.
Administrative and Outreach Core (AOC)
The AOC will organize, coordinate, and oversee the administrative and outreach activities of the INCLUDE Program. Administrative activities will include facilitating meetings, conference attendance and communications between the DCC, NIH, and key external stakeholders including but not limited to the Down syndrome community and the external Program Consultants, and developing procedures and policies for the operation of the DCC. Outreach activities will include establishing and maintaining a registry of investigators participating in the INCLUDE program and educating the research community on how to use the Data Hub through user training utilizing all available methods (e.g., in person, by webinar, through YouTube videos). The AOC will create quarterly newsletters to disseminate to the users about the INCLUDE DCC and its activities including future events. Equally important will be engaging users for their feedback in order to improve the functionality of the Data Hub and the overall DCC.
The activities of the DCC comprise areas of computer science, informatics and data management, but also require effective communication with the clinical or basic science communities to achieve its goals. This requires that the DCC have personnel with sufficient knowledge to serve as liaisons and translators among basic scientist, clinicians, and bioinformaticians and the Down syndrome community. The DCC is therefore expected to be composed of teams with expertise sufficient to allow them to function in this way. The areas of expertise included should also cover existing Down syndrome data as well as future Down syndrome datasets to be generated under INCLUDE, including the Down syndrome Cohort Development Program (DS-CDP). Additionally, in an effort to integrate tools and functions amenable to appropriate statistical analyses into the Data Hub, the Center should include data science and statistical epidemiology expertise within their team. The team should also have experience with phenotype ontology and harmonization, as well as experience in linking to a biospecimen repository(ies), for example through collaboration with the Federated Biobanking resource for the Down Syndrome Cohort Study Program (DS-CDP). In general, INCLUDE intends to prioritize the generation and collection of data from cohorts that are approved for broad data sharing and use, but recognizes that cohort data may involve a variety of data use limitations. The team should demonstrate experience handling all kinds of data modalities, including but not limited to clinical data, electronic health records (EHR) data, imaging data, mobile health data, social determinants’ data, be aware of international policies and regulations required to store and utilize data collected internationally as well as -omics data, including both short-read and long-read genomics data. In addition, the team should also demonstrate or provide a plan to implement emerging technologies such as Artificial Intelligence (AI) to their data integration and processing process, as well as making AI tools available on integrated cloud platforms.
Data Management Core (DMC)
The DMC will collect, process, harmonize, and facilitate the sharing of phenotypic, genomic and other -omics data generated from Down syndrome cohorts. To that end, it will be necessary to have a detailed understanding of diverse data types and the ability to manage quality control of the data. Integration of data from Down syndrome studies are of top priority; however, the DMC may seek to collect data from other sources with the intention of creating a comprehensive Down syndrome catalog, prioritizing datasets that are approved for broad sharing and use. In conjunction with activities led by NIH, the DMC will work with investigators to define standard data elements and establish a minimal common dataset in order to harmonize existing phenotypic data and organize the collection of prospective cohort data, which may require external collaboration with the new Down Syndrome Clinical Cohort Coordinating Center (DS-4C) and other parties. The data included in the INCLUDE Project are expected to increase as the number of participating cohorts increases, and the DMC will need to be able to adapt to handle different types of data using existing and emerging technologies. The DCC will not be expected to fund the sequencing and other -omics data acquisition related costs itself.
Another major function of the DMC will be to support a centralized Virtual Biorepository resource to coordinate a single online biospecimen repository or a network of DNA, tissue specimen and cell line repositories relevant to Down syndrome research. Working in collaboration with the future Federated Biobanking resource for the Down Syndrome Cohort Study Program (DS-CDP), the DMC is expected to coordinate standardization and indexing of biospecimen metadata to provide an integrated resource to the investigator community.
Data Management and Access Practices Under the Genomic Data Sharing Policy:
Developers who seek access to human genomic data generated and shared under the NIH Genomic Data Sharing (GDS) Policy (NOT-OD-14-124) are expected to request access through the NIH developer access process (see Implementation Update for Data Management and Access Practices Under the Genomic Data Sharing Policy (NOT-OD-24-157). The NIH developer access process sets expectations for the Lead Developer(s) (e.g., the Principal Investigator (PI) who is listed as the Project Director (PD) or PI on the funding application) and those they directly supervise to ensure GDS Policy participant protections, privacy, and oversight are maintained when accessing human genomic data under the GDS Policy.
Visit our Institutionally Limited Submission webpage for more updates and other announcements.