Key Dates

Related Announcements

PA-20-272 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)

RFA-RM-21-020 - Cutting Edge Informatics Tools for Illuminating the Druggable Genome (U01 Clinical Trial Not Allowed)

Issued by

Office of Strategic Coordination (Common Fund)

Purpose

This Notice is part of the Common Fund Program "Illuminating the Druggable Genome" (IDG;https://commonfund.nih.gov/idg/index), an initiative that aims to catalyze research to improve our understanding of the properties and functions of proteins that are currently not well studied within commonly drug-targeted protein families. The IDG Program is inviting investigators with relevant active research project grants and cooperative agreements to submit administrative supplements, according to PA-20-272 Administrative Supplements to Existing NIH Grants and Cooperative Agreements(Parent Admin Supp Clinical Trial Optional) for funded projects to incorporate and present single-cell data within the IDG Pharos (https://pharos.nih.gov) resource. Pharos and the underlying infrastructure manage knowledge about human proteins by accruing, abstracting, data and information available in the primary literature, databases, and other resources around the world to create an integrated resource. A major goal of the resource is to help the community prioritize and study understudied targets to determine its relevance in human health and disease. It is crucial to remember is that Pharos does not store primary data only processed and abstracted data.

Currently, a significant and highly useful datatype missing in Pharos is single-cell data. Supplement awarded under this Notice will help to enhance the utility of Pharos by adding this new datatype to the Pharos databases and undertake research to identify the best ways to display and use this data to further the underlying goal of the IDG program namely, incentivize the study of understudied targets.

This Notice will only accept supplement requests that do not propose clinical trials.

Background:

The human genome has revealed a great deal about the human proteome, though significant portions remain understudied that could have implications in various diseases. Only a subset of expressed proteins demonstrates the requisite properties to serve as targets for the development of therapeutics. While at the informatics level, genome- and proteome-wide tools can collate information and query all proteins, technical feasibility necessitates a narrower focus of experimental efforts into protein families for which there are definable understudied members along with existing technologies that can be readily adapted at the scale necessary for wholesale elucidation of their function and generation of tools. Specific targets under study experimentally within IDG can be found at https://druggablegenome.net.

The IDG Program inspires innovative research by revealing a number of new activities and potential drug targets amongst these understudied proteins. Moreover, it is anticipated that the IDG Program will enhance our understanding of on- and off-target effects by establishing functional relationships among understudied members of the commonly targeted IDG-eligible protein families.

Thus, the overall goal of the IDG Program is to catalyze research in areas of biology that are currently understudied but that have high potential to impact human health by:

• Identifying biochemical, cellular, or animal model phenotypes for understudied proteins from druggable gene families.
• Enabling further investigation of those proteins by providing reagents and tools.
• Generating, maintaining, and facilitating the use of a minable knowledge base.

The IDG Program is a Consortium made up of a Knowledge Management Center (KMC; RFA-RM-16-024), three Data and Resource Generation Centers (DRGCs; RFA-RM-16-026), a Resource Dissemination and Outreach Center (RDOC; RFA-RM-16-025), and Cutting Edge Informatics Tools (CEITs; RFA-RM-18-011) awardees. More information about the IDG Program can be found at https://commonfund.nih.gov/IDG. Individual awardee information can be found at DruggableGenome.net.
Specifically, the KMC aggregates knowledge from a protein-centric viewpoint across the entire human proteome, with an emphasis on the understudied non-olfactory GPCRs, protein kinases, and ion channels that are the focus of the experimental initiative. The KMC has developed a knowledge portal (Pharos, https://pharos.nih.gov) that includes aggregated data and metadata, a query interface, and deployed informatics tools, providing the scientific community access to resources developed by the IDG Consortium. Pharos currently covers a large number of data types and other resources and provides perspectives from targets, pathways, transcriptomics, PPI, model organism data, literature, small molecule, diseases etc.

Research Objectives
A valuable new datatype that will allow the scientific community to further interrogate the function of understudied proteins in disease is that obtained from single cells. NIH is encouraging the submission of applications for supplements to active grants to enable the processing, query and presentation for use by biologists of human single cell data. Projects submitted to this Notice should enable biologists to prioritize proteins for study based on expression patterns in tissue, systems and cell types. A number of practical aspects could be important, for example, creating the right balance between running processing pipelines vs using processed data from other resources often for IDG purposes innovation is in transforming and presenting effective summaries that conveys biologically useful derived data that can be used in designing further experimental work.
Though the choice of the pipeline that creates cell x gene matrix is important the innovative part for IDG purposes are the steps that follow the creation of such matrices. Specifically, how such matrices can be summarized effectively for downstream use by biologists who are interested in following up individual targets and their biomedical relevance to disease and health.
Examples of potential challenges to be addressed could include but are not limited to:

• Identifying suitable single cell datatypes (healthy or disease-states, spatially-resolved or dissociated cells, and whether measuring transcriptomics, epigenomic, proteomics, metabolites) and assessing quality of these datasets for suitability in addressing IDG-relevant questions.
• Identifying and expanding or adapting existing analytical pipelines that are accepted in the scientific community and not creating novel analytical methods.
• Suitable methods to store and query validated single-cell data as the volume of data grows over time.
• Creating effective summaries of data from multiple experiments covering multiple modalities of single cell data.
• Creation and optimization of methods to better present or visualize single-cell data that will maximize utility for biologists involved in prioritization of targets.
• Add value utilizing existing single cell resources that use community accepted cell names and ontologies. How to efficiently utilize pre-computing to convey differential expression or tissue specificity and other representations useful for biologists.

A major criterion of import for achieving the goals of the IDG Program and/or for utility of methods in Pharos is ease of maintenance of the resulting software. In other words, sustainable computational approaches and software development environments that can be sustained and grown by knowledgeable non-experts is essential and approaches addressing this will be considered high programmatic priority.
Researchers may find the API and other software engineering approaches currently in use in Pharos helpful.

Award Project Period
To be eligible, the parent award must be active in FY22, and the research proposed in the supplement can be requested for up to 2 years. Standard NIH policies for administrative supplements will apply. The earliest anticipated start date is October 1, 2021.

Budget

Supplement budget requests cannot exceed $175,000 in direct costs (excluding subcontract F&A) per year. Requests must reflect the actual needs of the proposed project. Modular and categorical budgets are permitted.

Eligible Individuals (Program Director/Principal Investigator)
Individual(s) must hold an active grant or cooperative agreement. For supplements to parent awards that include multiple PDs/PIs, the supplement may be requested by any or all of the PDs/PIs (in accordance with the existing leadership plan) and submitted by the awardee institution of the parent award.

Review Criteria
In addition to those described in PA-20-272, the following criteria will be considered:

• Does the PI(s)/PD(s) have expertise in analysis of single-cell data?
• Does the application propose to engage the community in obtaining feedback?
• Does the application exhibit sufficient knowledge of the Pharos software environment?
• Does the application describe a sufficiently justified sustainability plan beyond the maximum two year funding period?

Description of circumstances for which administrative supplements are available.

Application and Submission Information

Applications for this initiative must be submitted using the following opportunity or its subsequent reissued equivalent.

• PA-20-272 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)

All instructions in the SF424 (R&R) Application Guide and PA-20-272 must be followed, with the following additions:

• Application Due Date(s) June 15, 2021, by 5:00 PM local time of applicant organization.
• For funding consideration, applicants must include NOT-RM-21-019 (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.
• The Research Strategy section of the application is limited to 6 pages.
• Applications non-responsive to the terms of this Notice will be not be considered for this initiative.
• Applicants are strongly encouraged to contact the appropriate Institute or Center supporting the parent award to discuss the proposed project in the context of the parent award.

Inquiries

Please direct all inquiries to:
Email: DruggableGenome@mail.nih.gov