NHLBI TOPMed: Omics Phenotypes of Heart, Lung, and Blood Disorders (X01)

FAQs: Frequently Asked Questions


This Funding Opportunity Announcement (FOA) invites applications for access to NIH-funded capacity for genome-wide high throughput assays and other omics platforms for investigators wishing to study the genetic basis and omics signatures of common, complex heart, lung, and blood disorders. Successful applicants will provide biospecimens and receive whole genome sequence or other omics data. No funding will be provided for specimen preparation or data analysis. Successful applicants will also be required to deposit phenotypic data associated with their biospecimens in a public database such as dbGaP.

Please re-check this page periodically, as new questions and answers will continue to be added as applicable.

Omics Questions for the X01 FAQ (2017)

  1. Can I propose a large scale whole genome sequencing project to TOPMed?
    After funding whole genome sequencing of more than 120,000 DNA samples, NHLBI will significantly reduce the number of samples for WGS in future rounds of the X01, starting from the next receipt date, October 19, 2017. In general, we discourage applications asking for WGS on thousands of samples. Applicants interested in WGS projects should check existing studies in TOPMed website (https://www.nhlbiwgs.org/group/project-studies) and talk to NHLBI staff about the novelty and feasibility of their applications prior to submission.
  2. Can I propose trans-omics (transcriptome, methylome, proteome, and metabolome) measurements on thousands of subjects?
    Applicants need to provide strong rationale for why each omics-measurement is needed to answer their specific scientific questions relevant to NHLBI’s mission and how the sample size is calculated to meet the need. Having existing WGS data on the cohort is not a sufficient hypothesis/reason for obtaining other omics data. While we have not set an arbitrary limit on sample size, applicants are strongly encouraged to discuss the feasibility of their applications with NHLBI staff.
  3. Can I just propose other omics without WGS data in my application?
    In general, we will provide omics measurements only on samples that have or will have WGS data. Please contact NHLBI staff if you have a special case for consideration.
  4. What are the omics that can currently be requested by X01 Investigators?
    They are Whole Genome Sequencing (WGS), Epigenetics (methylation), RNA-seq, Metabolomics, and/or Proteomics.
  5. Are there any requirements for previous omics being included for an application?
    No, but the applicant should note previous technologies that could indicate sample quality, e.g. array based genotyping or Whole Exome Sequencing to indicate DNA quality, etc.
  6. Is there a minimal requirement for prior omics analysis?
    No. However, if the application includes WGS or other omics data generated elsewhere, investigators may need to address whether the existing data can be part of TOPMed in terms of data sharing, quality, and formats.
  7. What are the sample amounts for each omic platform?
  • WGS, 500 ng DNA for 20-30X coverage – PCR free preferred unless there is a specific reason for its use, such as stem cell investigations
  • Epigenetics (Infinium® MethylationEPIC 850K BeadChip.) – 1,000ng of genomic DNA for bisulfite array profiling
  • RNA-seq (45 million reads, 101 bp) – 1,000 ng RNA, RIN Score of 7 or better, indicate isolation method (including use of PAXGENE tubes if available) and sample source (e.g. whole blood, tissue, etc.)
  • Metabolomics (mass spectrometry) – 200 microliters. EDTA plasma is recommended. Applicants should provide a list of specific metabolites that would be required for their analysis.
  • Proteomics (SOMAmer or mass spectrometry) – 200 microliters.  EDTA plasma is recommended. Applicants should provide a list of specific proteins that would be required for their analysis and whether detection of post-translational modified or cleavage products is necessary.
  1. Where will the assays be performed?
    Details about the data generation centers will be provided after awards are made.
  2. What level of quality control will be done and where/who will do that?
    Details about the quality control will be provided after data generation centers are announced.
  3. Is it possible to communicate with the centers that will be performing the assays and QC so we can include that information in the X01 application in order to provide a compelling scenario for our later request for data analysis funds?
    No, as contracted vendors have not yet been selected for this round of omics.
  4. When will data generated be shared with the scientific community?
    All omics data will be made available to the scientific community 6 months after cleaned data is provided to the submitting study.
  5. Can investigators include requests for X01 “awards” in their R01 applications?
    No. Separate applications are required for X01 sequencing and omics support. If their X01 applications are selected, investigators can reference the X01 approval in their other grant applications. Investigators must inform the NHLBI if another source has subsequently funded or is likely to fund the studies proposed in their X01 application.
  6. Can investigators reference the data of other existing or on-going TOPMed projects as part of their X01 applications in order to increase the sample size for data analysis?
    Yes. NHLBI strongly encourages applicants to leverage existing TOPMed data in their research. Study descriptions can be obtained at https://www.nhlbiwgs.org/group/project-studies. All TOPMed data will be made available to the scientific community through the database of Genotypes and Phenotypes (dbGaP) (link is external) or an approved NIH data warehouse.