The purpose of this NOSI is to encourage applications that explore and/or test the role of gene networks in substance use disorders (SUD) through the development, optimization, and/or implementation of multilevel computational, bioinformatics, statistical and/or analytical approaches that integrate at least two levels of data (e.g. genomic, epigenomic, chromatin, environmental, etc.).

Background:

Many genetic loci, genetic pathways, epigenetic factors, and environmental conditions contribute to SUD. Recent large-scale ‘omics studies have uncovered an emerging repertoire of single nucleotide variants, copy number variants, gene expression changes and epigenetic alterations associated with SUD-relevant biological processes or behaviors. These studies underscore the complexity of the genetic/epigenetic architecture of SUD. They also highlight that the lack of analytical tools to tease out gene networks, gene x gene interactions, and the contributions of multi-level data comprises a major gap in understanding how these different types of data contribute to the pathophysiology and neurobiological causes of SUD.

Research Objectives:

Applicants may propose to create, use, and/or optimize bioinformatics tools, computational methods, and/or other statistical methods and analytics tools to integrate multi-level data that detect the gene networks involved in SUD. Studies should incorporate at least two types of data relevant to gene network analyses that address SUD-relevant biological processes or behaviors. SUDs of interest include those involving include: nicotine, cocaine, methamphetamine, opioids, cannabinoids, or combinations of these drugs. Applicants proposing to investigate alcohol in concert with one or more NIDA-relevant substances may also submit their application to this NOSI.

Studies may propose to collect new data or analyze data from previous studies. Possible types of data include (but are not limited to): genetic, epigenetic, molecular, proteomic, metabolomic, circuit-level molecular analyses, and/or environmental studies. As applications will span different disciplines (e.g. expertise in SUD-relevant phenotypes and behaviors, ‘omics, bioinformatics, computational biology, statistical analysis, and big data analytics, applicants are encouraged to assemble multidisciplinary teams that span the expertise required for successful completion of the project. Applicants should create open source databases, software, standards, platforms, etc. whenever possible and adhere to privacy and ethics concerns. All data should adhere to FAIR principles (e.g. findable, accessible, interoperable, and reusable) to enable secondary analyses by the scientific community. Projects should leverage the use of existing genetic resources whenever possible. Applicants should include strategies to test and confirm the findings for reproducibility and relevance to research on substance use disorders.

Research interests include, but are not limited to applications that propose to:

• Development of methods to integrate and analyze various types and sources of data, including genomic, epigenomic, molecular, proteomic, metabolomic, behavioral, or environmental
• Construction of software platforms capable of analyzing and/or integrating large, complex data sets commonly acquired in research involving the genetics and epigenetics of substance use disorders
• Use of automation, machine learning, and/or artificial intelligence to aggregate, mine, analyze, classify and/or integrate large ‘omics with behavioral, circuitry and/or environmental datasets
• Platforms for gene x gene and epistasis analyses
• Studies that delineate the longitudinal gene network changes along the SUD trajectory

Applications nonresponsive to terms of this NOSI will be not be considered for the NOSI initiative. Applications that are not responsive include:

• Applications that propose to analyze only one type of data
• Applications focused on generating gene sets via pathway analysis (e.g. IPA, DAVID, GeneGo/Metacore, etc.) from large-scale genomics studies
• Applications that propose large-scale gene discovery projects (e.g. GWAS, EWAS, eQTL, mQTL, and other similar studies)
• Applications focused solely on alcohol exposure

Application and Submission Information

This notice applies to due dates on or after June 5, 2020 and subsequent receipt dates through September 8, 2023.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.

• PA-19-055 - NIH Research Project Grant (Parent R01 Clinical Trial Required)
• PA-19-056 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
• PA-19-091 NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)
• PA-19-052: NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed)
  PA-19-053: NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)
  PA-18-591: 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 the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-DA-20-020” (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.

Applications nonresponsive to terms of this NOSI will be not be considered for the NOSI initiative.

Please direct all inquiries to the contacts in Section VII of the listed funding opportunity announcements with the following additions/substitutions:

Scientific/Research Contact(s)

Amy C. Lossie, PhD
National Institute on Drug Abuse (NIDA)
Telephone: (301) 827-6092
Email: amy.lossie@nih.gov