This FOA provides an opportunity for investigators to utilize biospecimen analysis capabilities supported by the National Human Genome Research Institute (NHGRI) RFA-HG-15-001 and NHLBI contracts to generate omics signatures for their own studies. Data generated through this program is expected to be shared with others in the scientific community, allowing investigators to leverage a rich collection of omics data accumulating in a common, publically accessible database. An overarching goal is to generate information that has greater collective scientific value than the individual studies in isolation. Applicants must have existing, high quality biospecimens collected from well-phenotyped human subjects in studies designed to inform the molecular pathobiology of disorders in heart, lung, and blood systems. At the beginning of this initiative, the capability will be mostly for the human whole genome sequencing (WGS), but we anticipate that capabilities will increase for other omics, including RNA-sequencing (RNA-seq), methylation profiling, metabolite-profiling, and proteomic-profiling as the respective technologies become more cost-effective. The ultimate goal is to transform HLB genomic science from simple genetic locus-trait associations to comprehensive understanding of complex disease pathobiology at a multi-omics, systems level. Information on the omics centers and assays will be updated in the webpage for frequently asked questions (FAQ).
This FOA is intended to support studies of common, complex disorders that significantly affect heart, lung, and blood (HLB) systems. Applicants should contact NHLBI staff prior to preparing an application to discuss the purpose and scope of their applications and to obtain updates regarding the technical requirements and analytical capabilities of the program. Applicants may, in a single application, apply to use one or more of the five omics assays listed above to accomplish a cohesive research goal. In accordance with the NIHGenomic Data Sharing Policy, all omics and related phenotypic data are expected to be shared with the broader research community through a public database such as dbGaP, consistent with achieving the goals of the program. Since dbGaP is built primarily for genotypic data, NIH may work with applicants to determine the details of how other omics datasets should be stored in dbGaP and/or other related databases supported by NIH. Successful applicants will be invited and expected to join NHLBI’s TOPMed consortium and participate in its advisory and collaborative discussions.
Whole Genome Sequencing (WGS). In general, WGS applications may aim to discover influential genetic variants underlying HLB disorders using various experimental designs (e.g., family-based, case-control, or a mix of both); if the same subjects for WGS also have other omics data, applicants may use integrative omics approaches to identify gene-regulatory networks or other functions of genomic variants. Currently, this FOA offers a standard protocol for sequencing whole human genome from high quality genomic DNA (preferably not whole genome amplified DNA). An NHLBI-designated informatics center will perform basic data processing, including variant-calling (e.g., SNPs, SNPs, and copy number variants (CNVs)) as well as submission of sequencing data to dbGaP. Applicants may also perform their own variant-calls if the standard variant-call is not appropriate to their research aims. For applicants with limited experience in or resources for handling genomic data, the sequencing centers and/or the NHLBI’s informatics center will be able to provide some genomic data analysis capacity, and those applicants will need to work with the centers to provide clinical measurements and other data required for phenotype-genotype analyses. For applications using large numbers of samples, applicants are encouraged, when possible, to divide sample collections into smaller, phased projects within a single application, starting with the minimum number of subjects needed for initial discovery. After approval to access the sequencing capacity, X01 applicants will work with NHLBI, NHGRI, and the sequencing centers to determine the timing and number of DNA samples to be sequenced.
Other Omics Assays. Omics data other than whole genome sequence (e.g., RNA, methylation, metabolites, and proteins) may be highly useful for studies of gene-gene and gene-environment interactions. Such studies benefit from the availability of datasets which contain multi-omics data and WGS data that have all been measured on the same subjects and which also include rich clinical and environmental measurements. Because the sample preparation protocols for other omics measures (RNA-seq, DNA methylation, metabolite-profiling, and protein profiling) are expected to be more complex than that for WGS, applicants are encouraged to consult the FAQ page and contact NHLBI staff for updated protocol specifications. Large scale applications are permitted, but applicants proposing large sample sizes are encouraged to organize their study as a series of phased projects involving a smaller number of samples in each phase, if possible.
Deadlines: January 19, 2016; January 19, 2017; January 19, 2018; January 18, 2019
Filed Under: Funding Opportunities