Department of Health
and Human Services (HHS)
and Human Services (HHS)
RESCINDED
November 17, 2020
NOT-HL-19-676 - Notice of Special Interest (NOSI): Integrative Omics Analysis of NHLBI TOPMed Data (Parent R01 Clinical Trial Not Allowed)
PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
National Heart, Lung, and Blood Institute (NHLBI)
This Notice of Special Interest is a reissue of NOT-HL-19-676.
Background and Purpose:
The symptom-based diagnosis and treatment of heart, lung, blood, and sleep (HLBS) diseases has vastly improved in recent years, yet an understanding of the molecular mechanisms underlying many of these diseases has remained elusive. Furthermore, in most cases the impact of genetic variation on severity of disease and treatment outcomes remains unknown. Therefore, the NHLBI has recently created the Trans Omics for Precision Medicine (TOPMed) program, which aims to utilize high throughput omics to characterize a variety of HLBS diseases. TOPMed is well on its way to collecting whole genome sequence from over 130,000 well-phenotyped individuals and is currently generating high-throughput expression and other omics data (e.g. RNA, DNA methylation, metabolites, and proteins) from many of these individuals to complement whole genome sequence information.
Having produced an unprecedented volume of high-throughput data, TOPMed now seeks to turn its attention to effectively leveraging this resource through novel systems biology analyses to uncover disease pathobiology. Although lower costs and technological improvements in sequencing technology have vastly expanded our ability to generate large volumes of omics data, the ability to analyze such large datasets to extract biologically meaningful insights from them remains challenging. Systems level models incorporating trans-omics analyses will be an important step in uncovering the underlying biological networks, gene-gene and gene-environment interactions influencing disease and treatment outcomes. Thus, advanced analyses that incorporate genotype and phenotype datasets from thousands to tens of thousands of individuals are required to move TOPMed to the next phase of discovery.
Research Objectives:
The trans-omics resource currently being built by the TOPMed program presents a unique set of challenges and opportunities for genomic analysis. Whole genome sequence coupled with expression and other deep clinical and molecular phenotyping data from tens of thousands of individuals promises to hold important information about rare and common genetic variants influencing disease. Several phases of data generation have brought together a collection of cohorts and studies that span a wide variety of HLBS diseases, geographic location, ethnic variation, and population structure. More information about participating studies can be found at https://www.nhlbiwgs.org/.
As this data resource gains maturity, analyses that effectively synthesize very large volumes of information from across many different datatypes remain scarce. NHLBI seeks to fund analyses that utilize existing TOPMed omics data to uncover the molecular mechanisms driving HLBS disease. Investigators are encouraged to utilize a systems approach incorporating computational modeling to bring together high throughput genotype and phenotype datasets. Analyses may incorporate new or existing data generated outside of TOPMed. However, this notice seeks studies that will use existing TOPMed data as the major resource for analysis of HLBS diseases and measures. Furthermore, applications seeking to utilize TOPMed data for use as controls, model testing, or solely for replication will not be prioritized. TOPMed has particular interest in questions about identifying associations between variants and disease phenotypes and analyses using existing functional data to reveal associations and/or make functional inferences. Investigators are encouraged to use the ethnic diversity of TOPMed for discovery and not merely for replication of findings in a single ethnic group.
Grants funded under this initiative will have access to data via dbGaP, including phenotype and genotype data, transcriptomics, methylation, metabolomics, and harmonized phenotypes produced by the TOPMed Data Coordinating Center (DCC) and jointly called sequence data generated by the TOPMed Informatics Research Center (IRC). Further information about the dbGaP data access application process can be found here: https://www.ncbi.nlm.nih.gov/books/NBK482114/#DArequest.would_you_give_me_a_stepbystep. Applicants are also encouraged to utilize emerging NHLBI cloud resources as they become available. This notice seeks to garner analysis of TOPMed data but not new tool development.
Suggested research examples include, but are not limited to:
Application and Submission Information
This notice applies to due dates on or after November 5, 2020 and subsequent receipt dates through May 8, 2023.
Submit applications for this initiative using the following funding opportunity announcement (FOA) or any reissue of this announcement through the expiration date of this notice
All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:
Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.
Scientific/Research Contact(s)
Weiniu Gan, Ph.D.
Division of Lung Diseases
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0202
Email: [email protected]
Pankaj Qasba, Ph.D.
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0050
Email: [email protected]
Mollie Minear, Ph.D.
Division of Cardiovascular Sciences
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0448
Email: [email protected]