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The purpose of this Funding Opportunity Announcement (FOA) is to create rodent reporter models for testing in vivo genome editing technologies, and to use these animal models to test genome editing delivery technologies and new genome editors developed under RFA-RM-18-016 and RFA-RM-18-017. The deliverables from the initiative will be a set of animal models (mice and rat), containing one or more reporter genes expressed in all cell types, that will allow facile and quantitative evaluation of genome editing in any cell type of interest. The Testing Centers will use these models to validate new delivery systems and genome editing tools developed by other investigators in the Somatic Cell Genome Editing Program. The creation and testing of these rodent models will accelerate the translation of genome editing technologies into treatments for human diseases.

The National Human Genome Research Institute (NHGRI) seeks applications for the production of High Quality Human Reference Genomes (HQRG) as a component of the NHGRI Human Genome Reference Program (HGRP). One aim of the HGRP is to develop a genome reference that is representative of human population genetic diversity. To help achieve this goal, this HQRG initiative is expected to establish metrics for high quality-genome assemblies; collaborate with other HGRC awardees on sample selection and prioritization; produce on the order of 350 high quality haplotype-resolved human genomes, using diverse samples consented for full data release; and provide capacity to help resolve error reports received by the HGRC.

The purpose of this initiative is to support Genomic Centers for Infectious Diseases (GCID) to promote broad use and expand the application of genomics technologies and computational analysis to understand infectious diseases, with an emphasis on pathogens, their interaction with the host and microbiome, and to aid in the development of novel genomics-based tools to diagnose, prevent and treat infectious diseases. The GCID will support innovative technology development in all aspects of genomics, including the use of synthetic and genome editing technologies as well as functional genomics to address basic, translational, and clinically relevant questions in host-pathogen interactions. The knowledge generated, including research data, analytical software tools, computational models, experimental protocols, and reagents, is expected to be widely disseminated to the scientific community through publicly accessible databases and reagent repositories.

This Funding Opportunity Announcement (FOA) seeks grant applications to develop major advances in genomic technologies. Advances in genomics and more broadly in biomedical research have been greatly facilitated by significant and sustained genomics technology throughput increases, cost decreases, and improvements in ease of use. The proposed technology development work should allow comprehensive genomic analysis of features not assayable today, or an increase of no less than an order of magnitude improvement in an existing technology in terms of data quality, throughput, efficiency or comprehensiveness (individually or in combination). This FOA explicitly excludes the development of novel technologies for DNA sequencing and for direct RNA sequencing; those projects should respond to a parallel set of FOAs (RFA-HG-18-001, RFA-HG-18-002, and RFA-HG-18-003).

The NIH Common Fund has established the Gabriella Miller Kids First Pediatric Research Program (Kids First) to develop a pediatric research data resource populated by genome sequence and phenotypic data that will be of high value for the communities of investigators who study the genetics of childhood cancers and/or structural birth defects. Kids First has established and continues to develop a Data Resource including a collection of curated genomic and phenotypic data from childhood cancer and structural birth defects cohorts and a central portal where these data and analysis tools are accessible to the research community. Access to these data will promote comprehensive and cross-cutting research and collaboration leading to more refined diagnostic capabilities and ultimately more targeted therapies. This FOA is intended to support meritorious small research projects focused on analyses of childhood cancer and/or structural birth defects genomic datasets generated by the Kids First program and/or associated phenotypic datasets. Development of approaches, tools, or algorithms appropriate for analyzing genomic, phenotypic, and/or clinical data relevant to Kids First may also be proposed

This Funding Opportunity Announcement (FOA) encourages applications from integrative teams and individual investigators for large-scale complex multi-disciplinary Functional Genomics Projects (FGPs) to determine the contributions and mechanisms underlying the contribution of risk-associated variants and their downstream effector transcripts for type 2 diabetes (T2D). The intent is to generate knowledge and tools to enable the identification of putative biomarkers and therapeutic targets by future efforts. Genome-wide association studies (GWAS) and other genomic studies of T2D and its complications have found many variants that are statistically associated with disease risk, disease protection, progression to complications, or other traits. However, such studies do not show which variants in genomic elements cause these effects or how they result in differences in function. Applications submitted to this RFA will systematically identify causal variants and effector transcripts associated with all known T2D risk variants, verify the role of downstream effector transcripts, build network models that explain their role(s) in T2D and its complications, and identify key readouts and modulation points in these networks. Data, tools, and reagents generated by these projects will be released rapidly to facilitate more in-depth study by the broad scientific community.

This Funding Opportunity Announcement (FOA) encourages applications from integrative teams and individual investigators for large-scale complex multi-disciplinary Functional Genomics Projects (FGPs) to determine the contributions and mechanisms underlying the contribution of associated variants for type 1 diabetes (T1D). Genome-wide association studies (GWAS) and other genomic studies of T1D have found many variants that are statistically associated with disease risk or disease protection, but they have not clearly shown which variants in genomic elements cause these effects or how they result in differences in function. Applications submitted to this RFA will systematically identify causal variants and effector transcripts associated with all known T1D risk variants, verify the role of downstream effector transcripts, build network models that explain their role(s) in T1D. These biological insights could lead to the development of reliable biomarkers and effective strategies for screening and disease prevention, rational drug design, and better tailored therapies.

This Funding Opportunity Announcement (FOA) encourages applications from integrative teams and individual investigators for large-scale complex multi-disciplinary Functional Genomics Projects (FGPs) to determine the contributions and mechanisms underlying the contribution of associated variants for type 1 diabetes (T1D). Genome-wide association studies (GWAS) and other genomic studies of T1D have found many variants that are statistically associated with disease risk or disease protection, but they have not clearly shown which variants in genomic elements cause these effects or how they result in differences in function. Applications submitted to this RFA will systematically identify causal variants and effector transcripts associated with all known T1D risk variants, verify the role of downstream effector transcripts, build network models that explain their role(s) in T1D. These biological insights could lead to the development of reliable biomarkers and effective strategies for screening and disease prevention, rational drug design, and better tailored therapies.

NHGRI invites applications for research developing comparative approaches that can be used to understand genome structure and function and the relationship between genomic features and phenotypes. This program supports studies that enable the use of a diverse array of species to advance our ability to understand basic biological processes related to human health and disease, as well as studies that develop novel analytical tools and resources for the comparative genomics research community.

There are two main purposes of the Rat Opioid Genome Project. The first is to tease out genetic, genomic, and molecular (epi)genetic variants that underlie phenotypes associated with distinct stages along the opioid use disorder (OUD) trajectory to identify potential targets for future interventions at early stages along the trajectory. The second is to identify genetic, genomic, and molecular (epi)genetic variants underlying comorbid conditions and/or phenotypes that can be used to develop therapeutics to save lives of people who are at the end stages of the OUD trajectory.

REISSUE of PAR-18-733 The NIH Common Fund has established the Gabriella Miller Kids First Pediatric Research Program (Kids First) to develop a pediatric research data resource populated by genome sequence and phenotype data that will be of high value for the communities of investigators who study the genetics of childhood cancers and/or structural birth defects. The overall goal of the Gabriella Miller Kids First Pediatric Data Resource is to help researchers understand the underlying mechanisms of these conditions, leading to more refined diagnostic capabilities and ultimately more targeted therapies, as well as to develop an integrated pediatric research data resource by obtaining and aggregating genome sequence and phenotype data for as many relevant structural birth defects and pediatric cancer cohorts as possible and to advance research in this area through the broad sharing of these data with the research community. This FOA is intended to promote meritorious small research projects focused on the development and analyses of childhood cancer and/or structural birth defects datasets that are part of the Kids First Data Resource or could be included in the Kids First Data Resource. Development of statistical methodology appropriate for analyzing genome-wide data relevant to childhood cancer and/or structural birth defects may also be proposed.

 The objective of this FOA is to support research in the discovery and characterization of the full spectrum of human-specific non-coding functional genomic elements across brain regions, cell types, and developmental time periods to elucidate their role(s) in the molecular pathophysiology of mental illness. It is expected that projects under this FOA will apply unbiased genome-wide approaches, computational methods, and experimental assays to identify and characterize functional genomic elements in both healthy and diseased human brains to correlate findings with development of mental illnesses and outcomes relevant to brain function and dysfunction.

Epidemiological studies have shown that psychiatric disorders, constitute a significant public health burden across diverse populations worldwide. These mental disorders are characterized by marked genetic heterogeneity, with both common and rare variation contributing to the complex phenotypic outcomes. For reasons such as population homogeneity and ease of ascertainment, most genome-wide genetic studies to date have mainly focused on cohorts of European-ancestry, however, no single population is sufficient to fully uncover the variants underlying neuropsychiatric diseases in all populations. The absence of diverse ancestries in genome-wide association studies has therefore negatively impacted their ability to illuminate the full genetic architecture of complex neuropsychiatric traits. Populations with different ancestral origins vary in terms of allele frequencies, biological adaptations, and other properties that affect the detectability and importance of risk variants. Lack of ancestrally diverse genome-wide data can lead to the misidentification of causal variants due to cryptic population stratification or simply overlooking a causal variant altogether, since rare variants are likely to be more recent in origin and more geographically localized.

The purpose of this Funding Opportunity Announcement (FOA) is to establish one or two centers that can rapidly generate high quality whole genome sequence and variant data from a large number of human specimens representing two types of pediatric conditions - childhood cancers and structural birth defects.  All sequence data generated under this FOA will be re-processed and harmonized by the Gabriella Miller Kids First Pediatric Data Resource Center (Kids First DRC), which is also charged with building a public-facing, web-based portal that will allow researchers to search, access, aggregate, analyze, and share annotated genomic sequence, variant, and phenotypic datasets.  Together these resources will promote comprehensive and cross-cutting research and collaboration within the pediatric research community.

The overarching goal of this FOA is to add informatics capabilities to the Common Fund program, Illuminating the Druggable Genome (IDG; https://commonfund.nih.gov/idg/index). The IDG consortium's purpose is to facilitate the unveiling of the functions of selected understudied proteins in the Druggable Genome using experimental and informatics approaches. Currently, this research consortium is composed of multiple Data and Resource Generation Centers (DRGCs), a Knowledge Management Center (KMC), and a Resource Dissemination and Outreach Center (RDOC). The purpose of this specific FOA is to solicit applications to build a set of Cutting Edge Informatics Tools (CEITs) that will augment the capability of the KMC as well as the broader IDG Consortium in two ways: (1) by deploying tools to enhance the communitys ability to process, analyze, visualize data, to prioritize new data resources and methods to be incorporated into Pharos that will strengthen predictions about physiological and disease associations around the understudied proteins and (2) to prioritize physiological and disease relevant cellular and animal models for further study of the understudied proteins (non-olfactory GPCRs, protein kinases, and ion channels) both within the IDG program and by the larger community.

The purpose of this funding opportunity announcement (FOA) is to stimulate clinical research that applies a social genomics approach to chronic wound risk, presence, progression, and healing. The field of social genomics focuses on how the social environment influences gene expression, and how this gene expression may in turn impact health outcomes. Chronic wounds (e.g., diabetic ulcers, venous or arterial ulcers) are multidimensional and, as such, there is benefit to a holistic approach that goes beyond a focus on the wound (i.e., repairing the skin and underlying tissue) to include an approach that focuses on the person with the wound. A better understanding of social environmental factors (positive and negative) and associated molecular mechanisms is needed to advance therapeutic strategies aimed at reducing chronic wound risk in addition to improving healing outcomes and quality of life.

This Funding Opportunity Announcement (FOA) invites applications specific to sample acquisition, genome wide association studies, whole genome sequencing, quality control checking, variant calling, and data calling that will support the generation of data for the Alzheimer's Disease Sequencing Project Follow-Up Study.  

Genetic and genomic studies have identified genes and gene variants that may impact the fundamental biological mechanisms underpinning substance use disorders (SUDs).  Discovery of these genes/variants, while extremely valuable, is only the first step in understanding the molecular processes that influence SUDs. This Funding Opportunity Announcement (FOA) encourages basic functional genetic and genomic research in two areas:  1. functional validation to determine which candidate genes/variants/epigenetic/non-coding RNA features have an authentic role in SUDs, and 2. detailed elucidation of the molecular pathways and processes modulated by candidate genes/variants, particularly for those genes with an unanticipated role in SUDs.   

This Funding Opportunity Announcement (FOA) invites applications specific to sample acquisition, genome wide association studies, whole genome sequencing, quality control checking, variant calling, and data calling that will support the generation of data for the Alzheimer's Disease Sequencing Project Follow-Up Study.

The purpose of this specific FOA is to solicit applications to develop and implement a Knowledge Management Center (KMC) for the Illuminating the Druggable Genome (IDG) Program. The KMC will house, organize, and share metadata and data by accruing and abstracting data and information available in primary literature, databases, and other resources around the world and deploy an integrated informatics solution. However, any proposed human curation efforts will initially focus only on illuminating three major protein families of the IDG project:  non-olfactory G protein-coupled receptors, ion channels and protein kinases. The KMC will identify and scientifically justify the data and resources it proposes to accrue that will enable the biomedical community to easily identify and prioritize protein targets within any gene family to study further. The KMC awardee will be expected to interact and collaborate with all future awardees of the IDG Program, the IDG Consortium, and, future awardees of the IDG CEITs.