Single Cell Opioid Responses in the Context of HIV (SCORCH) Program: Data Mining and Functional Validation (R21 Clinical Trial Not Allowed) | RFA DA 25 017

Frequently Asked Questions (FAQs)

What is the SCORCH Program: Data Mining and Functional Validation funding opportunity (RFA-DA-25-017)?

This opportunity is an NIH discretionary grant focused on accelerating discovery that links large-scale single-cell and related omics datasets from the SCORCH program to testable biological mechanisms. The core idea is to mine existing SCORCH data for high-value molecular leads tied to HIV infection, antiretroviral therapy (ART), and substance use disorders (SUD), including opioid-related effects, and then perform focused validation to determine which leads are likely to matter biologically and therapeutically.

What grant mechanism does this opportunity use?

The opportunity uses the NIH R21 mechanism.

Are clinical trials allowed under this funding opportunity?

No. Clinical trials are not allowed under this funding opportunity.

What is the main purpose of the program?

The purpose is to connect SCORCH single-cell and related omics data resources to concrete, testable biology. This includes extracting and prioritizing candidate molecular signals and then validating them to produce credible mechanistic insights related to HIV, ART exposure, and SUD (including opioid effects), especially where single-cell resolution can reveal biology that is not visible in bulk analyses.

What does "data mining" mean in the context of this opportunity?

Data mining here refers to analyzing existing SCORCH datasets to identify specific cellular and regulatory features associated with molecular responses to HIV/ART or SUD. The emphasis is on targeted discovery rather than descriptive cataloging, with the goal of identifying the most compelling cell types, cell states, genes, regulatory elements, and networks implicated in the biology of interest.

What kinds of biological features are applicants expected to identify from SCORCH datasets?

Applicants are expected to use SCORCH data to pinpoint relevant cell types and cell states and to identify molecular signals such as transcripts (gene expression changes), enhancers (regulatory DNA elements), and broader transcriptional networks (coordinated gene programs and regulatory circuitry) that are linked to HIV/ART biology, SUD/opioid exposure, or their intersection.

Is the program focused on describing datasets, or on making testable discoveries?

The intent is not just descriptive cataloging. The initiative emphasizes targeted discovery: identifying components strongly associated with HIV-related biology, ART exposure, opioid/SUD exposure, or their overlap, and doing so in a way that leads to testable hypotheses.

What is meant by "functional validation" in this announcement?

Functional validation means moving beyond computational findings to test whether prioritized candidates (such as cell types, genes, enhancers, or networks) have a causal or biologically meaningful role in HIV/ART or SUD molecular responses. The goal is to distinguish real drivers, modulators, or biomarkers from analytical artifacts.

What validation approaches are highlighted as examples?

The announcement highlights approaches such as epigenomic or transcriptomic manipulation (for example, perturbing regulatory elements or gene expression programs) and high-throughput secondary screening strategies to efficiently confirm or rule out candidate mechanisms.

What types of outputs is this R21 opportunity aiming to produce?

Although R21 awards are typically exploratory and time-limited, this opportunity is structured to support projects that produce actionable outputs such as validated targets, clarified pathways, and reproducible analytical frameworks that other researchers can extend toward translational or preclinical development.

What scientific areas does the opportunity specifically target?

The opportunity targets the intersecting biology of HIV infection, antiretroviral therapy (ART), and substance use disorders (SUD), including opioid-related effects. It particularly values insights that benefit from single-cell resolution and that illuminate how these exposures shape molecular processes in specific cell populations and regulatory programs.

Does the opportunity relate to therapeutic development?

Yes, indirectly. The longer-term goal is to build foundational mechanistic knowledge and generate validated targets that can lay groundwork for downstream therapeutic development related to SUD or HIV, including therapeutic angles relevant to NeuroHIV cognitive phenotypes.

What role do SCORCH datasets play in proposed projects?

SCORCH datasets are central to the project concept. Applicants are expected to use SCORCH data resources as the basis for identifying high-value molecular leads and then carry out focused laboratory or computational validation to determine which leads are mechanistically meaningful.

Who is eligible to apply?

Eligibility is broad and includes many types of U.S. organizations and some non-U.S. entities. Eligible applicants include various government entities (state, county, city or township, special districts), independent school districts, public and state-controlled institutions of higher education, private institutions of higher education, federally recognized Native American tribal governments, other Native American tribal organizations, public housing authorities/Indian housing authorities, nonprofits (with or without 501(c)(3) status, outside higher education), for-profit organizations (other than small businesses), small businesses, and other NIH-specified categories.

Are organizations serving underrepresented populations explicitly included in the eligible applicant types?

Yes. The announcement explicitly calls out additional eligible applicant types such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), and Tribally Controlled Colleges and Universities (TCCUs).

Are faith-based or community-based organizations eligible?

Yes. Faith-based or community-based organizations are explicitly listed among eligible applicant types.

Can non-U.S. entities apply?

Yes. The eligibility list explicitly includes non-domestic (non-U.S.) entities.

Are U.S. territories or possessions included in eligibility?

Yes. U.S. territories or possessions are explicitly included.

Are eligible federal agencies mentioned as eligible applicants?

Yes. Eligible federal agencies are explicitly listed among eligible applicant types.

What is the original closing date provided for this opportunity?

The original closing date provided is 2024-08-13.

What is the award ceiling listed in the provided information?

The award ceiling listed is 275000.

What CFDA number is associated with this opportunity?

The opportunity is classified under CFDA 93.279.

What activity categories are associated with the opportunity?

The activity categories listed are education and health.

What makes this opportunity distinct from other data analysis-focused grants?

This opportunity explicitly combines two expectations: (1) targeted data mining of existing SCORCH single-cell and related omics datasets to identify high-value, specific molecular and cellular leads; and (2) functional validation steps to test whether those leads are mechanistically meaningful in HIV/ART and/or SUD biology. The emphasis is on producing validated, credible targets and pathways rather than generating purely descriptive analyses.

What kinds of biological questions is the program trying to answer at single-cell resolution?

The program is trying to clarify how SUD and/or HIV/ART shape molecular processes at the level of specific cell populations and regulatory programs. Single-cell resolution is emphasized because it can reveal effects within particular cell types and cell states that may be masked in bulk tissue analyses.