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19: Genomics - Biology

19: Genomics - Biology


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Genomics is a field that studies the entire collection of an organism’s DNA or genome. Since sequencing has become much less expensive and more efficient, vast amounts of genomic information is now available about a wide variety of organisms, but particularly microbes, with their smaller genome size. In fact, the biggest bottleneck currently is not the lack of information but the lack of computing power to process the information!

Sequencing

Sequencing, or determining the base order of an organism’s DNA or RNA, is often one of the first steps to finding out detailed information about an organism. A bacterial genome can range from 130 kilobase pairs (kbp) to over 14 Megabase pairs (Mbp), while a viral genome ranges from 0.859 to 2473 kbp. For comparison, the human genome contains about 3 billion base pairs.

Shotgun sequencing

Shotgun sequencing initially involves construction of a genomic library, where the genome is broken into randomly sized fragments that are inserted into vectors to produce a library of clones. The fragments are sequenced and then analyzed by a computer, which searches for overlapping regions to form a longer stretch of sequence. Eventually all the sequences are aligned to give the complete genome sequence. Errors are reduced because many of the clones contain identical or near identical sequences, resulting in good “coverage” of the genome.

Shotgun Sequencing. By Commins, J., Toft, C., Fares, M. A. [CC BY-SA 2.5], via Wikimedia Commons

Second generation DNA sequencing

Second-generation DNA sequencing uses massively parallel methods, where multiple samples are sequenced side-by-side. DNA fragments of a few hundred bases each are amplified by PCR and then attached to small bead, so that each bead carries several copies of the same section of DNA. The beads are put into a plate containing more than a million wells, each with one bead, and the DNA fragments are sequenced.

Third- and fourth-generation DNA sequencing

Third-generation DNA sequencing involves the sequencing of single molecules of DNA. Fourth-generation DNA sequencing, also known as “post light sequencing,” utilizes methods other than optical detection for sequencing.

Bioinformatics

After sequencing, it is time to make sense of the information. The field of bioinformatics combines many fields together (i.e. biology, computer science, statistics) to use the power of computers to analyze information contained in the genomic sequence. Locating specific genes within a genome is referred to as genome annotation.

Open Reading Frames (ORFS)

An open reading frame or ORF denotes a possible protein-coding gene. For double-stranded DNA, there are six reading frames to be analyzed, since the DNA is read in sets of three bases at a time and there are two strands of DNA. An ORF typically has at least 100 codons before a stop codon, with 3’ terminator sequences. A functional ORF is one that is actually used by the organism to encode a protein. Computers are used to search the DNA sequence looking for ORFs, with those presumed to encode protein further analyzed by a bioinformaticist.

It is often helpful for the sequence to be compared against a database of sequences coding for known proteins. GenBank is a database of over 200 billion base pairs of sequences that scientists can access, to try and find matches to the sequence of interest. The database search tool BLAST (basic local alignment search tool) has programs for comparing both nucleotide sequences and amino acid sequences, providing a ranking of results in order of decreasing similarity.

BLAST Results.

Comparative Genomics

Once the sequences of organisms have been obtained, meaningful information can be gathered using comparative genomics. For this genomes are assessed for information regarding size, organization, and gene content.

Comparison of the genome of microbial strains has given scientists a better picture regarding the genes that organisms pick up. A group of multiple strains share a core genome, genes coding for essential cellular functions that they all have in common. The pan genome represents all the genes found in all the members of species, so provides a good idea of the diversity of a group. Most of these “extra” genes are probably picked up by horizontal gene transfer.

Comparative genomics also shows that many genes are derived as a result of gene duplication. Genes within a single organism that likely came about because of gene duplication are referred to as paralogs. In many cases one of the genes might be altered to take on a new function. It is also possible for gene duplication to be found in different organisms, as a result of acquiring the original gene from a common ancestor. These genes are called orthologs.

Functional Genomics

The sequence of a genome and the location of genes provide part of the picture, but in order to fully understand an organism we need an idea of what the cell is doing with its genes. In other words, what happens when the genes are expressed? This is where functional genomics comes in – placing the genomic information in context.

The first step in gene expression is transcription or the manufacture of RNA. Transcriptome refers to the entire complement of RNA that a cell can make from its genome, while proteome refers to all the proteins encoded by an organisms’ genome, in the final step of gene expression.

Microarrays

Microarrays or gene chips are solid supports upon which multiple spots of DNA are placed, in a grid-like fashion. Each spot of DNA represents a single gene or ORF. Known fragments of nucleic acid are labeled and used as probes, with a signal produced if binding occurs. Microarrays can be used to determine what genes might be turned on or off under particular conditions, such as comparing the growth of a bacterial pathogen inside the host versus outside of the host.

Proteomics

The study of the proteins of an organism (or the proteome) is referred to as proteomics. Much of the interest focuses on functional proteomics, which examines the functions of the cellular proteins and the ways in which they interact with one another.

One common technique used in the study of proteins is two-dimensional gel electrophoresis, which first separates proteins based on their isoelectric points. This is accomplished by using a pH gradient, which separates the proteins based on their amino acid content. The separated proteins are then run through a polyacrylamide gel, providing the second dimension as proteins are separated by size.

Structural proteomics focuses on the three-dimensional structure of proteins, which is often determined by protein modeling, using computer algorithms to predict the most likely folding of the protein based on amino acid information and known protein patterns.

Metabolomics

Metabolomics strives to identify the complete set of metabolic intermediates produced by an organism. This can be extremely complicated, since many metabolites are used by cells in multiple pathways.

Metagenomics

Metagenomics or environmental genomics refers to the extraction of pooled DNA directly from a specific environment, without the initial isolation and identification of organisms within that environment. Since many microbial species are difficult to culture in the laboratory, studying the metagenome of an environment allows scientists to consider all organisms that might be present. Taxa can even be identified in the absence of organism isolation using nucleic acid sequences alone, where the taxon is known as phylotype.

Key Words

genomics, sequencing, shotgun sequencing, genomic library, second generation DNA sequencing, massively parallel methods, third- and fourth-generation DNA sequencing, bioinformatics, genome annotation, open reading frame/ORF, functional ORF, GenBank, BLAST/basic local alignment search tool, comparative genomics, core genome, pan genome, paralog, ortholog, functional genomics, transcriptome, proteome, microarray/gene chips, probe, proteomics, functional proteomics, two-dimensional gel electrophoresis, structural proteomics, metabolomics, metagenomics/environmental genomics, metagenome, phylotype.

Study Questions

  1. What does the field of genomics encompass?
  2. What is shotgun sequencing and how does this allow for the complete sequencing of an organism’s genome?
  3. What are the basic differences among 2nd, 3rd, and 4th generation sequencing?
  4. What is an open reading frame and how can scientists use it to determine information about a genome and its products?
  5. How does functional genomics differ from comparative genomics? What are the tools used in functional genomics and what information can be obtained from each?

Systems Biology Approaches for Therapeutics Development Against COVID-19

Understanding the systems biology approaches for promoting the development of new therapeutic drugs is attaining importance nowadays. The threat of COVID-19 outbreak needs to be vanished for global welfare, and every section of research is focusing on it. There is an opportunity for finding new, quick, and accurate tools for developing treatment options, including the vaccine against COVID-19. The review at this moment covers various aspects of pathogenesis and host factors for exploring the virus target and developing suitable therapeutic solutions through systems biology tools. Furthermore, this review also covers the extensive details of multiomics tools i.e., transcriptomics, proteomics, genomics, lipidomics, immunomics, and in silico computational modeling aiming towards the study of host-virus interactions in search of therapeutic targets against the COVID-19.

Keywords: COVID-19 coronavirus database (DB) in silico multiomics pathogenicity systems biology.


19: Genomics - Biology

The rapidly unfolding events in New York and globally, emphasize the need to quickly decode the host-pathogen biology of SARS-CoV-2 and the associated COVID-19 disease. Among the science proposed in the community is understanding the evolution of the viral genome and possible host genomic factors from the germline or immune response, which may explain pathophysiology of COVID-19. New York is fortunate to have many experts in each of the relevant areas at all institutions. We believe the best chance of rapid progress will come from pooling efforts and resources across centers. To assist with this effort, the New York Genome Center is proposing the establishment of a city-wide genomics-focused research network to bring the genomics capacity and expertise in conjunction with area research programs on COVID-19. We believe these efforts, if well-coordinated and described, will be in position to rapidly attract the resources needed to enact them.

NYGC is proposing the following initial areas of intramural/extramural scientific focus and network capacity, and we would welcome concrete proposals in additional areas:

    • Large scale full length viral sequencing to determine viral evolution and spread across the community – As the virus is currently estimated to acquire approximately one new RNA mutation every 2 weeks, or every 2-3 transmissions, one can use the pattern of sequence variation to determine how far back any two infections can be traced to a single host and, with deep enough sampling, estimate where that host was and how the virus has moved through human populations. Such data could also be used to estimate important factors for epidemiological models such as how many introductions of the virus have occurred in a specific region and the number of unique clusters of transmission. These data will also provide insights to the number of undetected cases that are currently transmitting in the population.
      • Whole genome germline sequencing and immune repertoire sequencing of affected individuals, focused on extreme phenotypes to examine host factors and immune responses – Although the age and co-morbidity cofactors for COVID-19 have revealed high mortality rates in individuals of older age and those with pre-existing immune, cardiovascular or lung diseases, a striking observation is respiratory failure in some otherwise healthy young individuals. A known risk factor appears to be heavy exposure to viral load especially among frontline healthcare workers. It is likely germline variation will explain some aspects of extreme responses to SARS-CoV-2, which may in turn guide risk mitigation, vaccine development and implementation, and other strategies. Possibilities include DNA sequence polymorphisms that influence protein function and/or outlier gene expression in ACE2, TMPRSS2, and other proteins involved in viral entry, genes controlling surfactant alveolar cell development and function, polymorphisms in HLA, innate, or cellular immune responses, polymorphisms affecting cardiovascular function, intracellular RNA processing and others. Host-pathogen interaction with the genotype of the viral load may also be important, thus knowledge of both the viral sequences present, as well as host factors will be crucial. The information obtained could not only be impactful in the current pandemic but could also inform future pandemics.
        • Single cell sequencing to examine tissue responses and provide a genome variation of expression context for viral responses.
          • Establishment of a data commons for the research network so that full availability of data to investigators can be provided.


          To achieve progress in this critical research, we propose organizing a network of treatment and research sites in the New York area to share samples and data.
          Viral and germline samples from patients could be prepped at hospitals and sequenced in a distributed or centralized manner, and the data shared across all participating sites. This network would be open to any site seeing patients and any site with research capacity. We have already joined in a number of local efforts but joining together as one NYC/NJ-based COVID-19 research initiative would bring a strength in numbers and resources that we could all benefit from. A collective effort could quickly establish the optimal infrastructure required to do this effectively. There are many challenges of such an effort including identifying, recruiting and consenting interested participants, collecting and processing samples, rapid data analysis and data sharing. There are many people in New York with the necessary experience in organizing large studies to make this a success, several of whom have already begun to make progress on COVID-19 related research. I hope you will all agree with the importance of building this network and join. I would like to offer our help in organizing a centralized effort, we could be a site for sequencing and analysis, as well as provide help coordinating effective data sharing.

            • We would like to identify from each interested institution one clinical lead and one research lead with whom we could engage to help shape the network.
              • We host a call every other Monday at 2pm with all interested parties. If there are researchers or clinicians at your institution that would be interested, please forward this to them. If you would like to join the call, please email [email protected] to be added to the invite.

              We are aware of a wide range of ongoing research at your institutions and hope to have the opportunity to work together. If there are other ongoing research projects, activities and ideas that would benefit from a concerted and cooperative research program, please connect them with us and/or bring them up at the meeting. If there is sufficient interest and enthusiasm for a city-wide effort, we can begin building the means of communication and coordination.

              I look forward to hearing from all of you,

              Tom Maniatis, PhD
              Scientific Director and CEO
              New York Genome Center


              Genomic Study Points to Natural Origin of COVID-19

              No matter where you go online these days, there’s bound to be discussion of coronavirus disease 2019 (COVID-19). Some folks are even making outrageous claims that the new coronavirus causing the pandemic was engineered in a lab and deliberately released to make people sick. A new study debunks such claims by providing scientific evidence that this novel coronavirus arose naturally.

              The reassuring findings are the result of genomic analyses conducted by an international research team, partly supported by NIH. In their study in the journal Nature Medicine, Kristian Andersen, Scripps Research Institute, La Jolla, CA Robert Garry, Tulane University School of Medicine, New Orleans and their colleagues used sophisticated bioinformatic tools to compare publicly available genomic data from several coronaviruses, including the new one that causes COVID-19.

              The researchers began by homing in on the parts of the coronavirus genomes that encode the spike proteins that give this family of viruses their distinctive crown-like appearance. (By the way, “corona” is Latin for “crown.”) All coronaviruses rely on spike proteins to infect other cells. But, over time, each coronavirus has fashioned these proteins a little differently, and the evolutionary clues about these modifications are spelled out in their genomes.

              The genomic data of the new coronavirus responsible for COVID-19 show that its spike protein contains some unique adaptations. One of these adaptations provides special ability of this coronavirus to bind to a specific protein on human cells called angiotensin converting enzyme (ACE2). A related coronavirus that causes severe acute respiratory syndrome (SARS) in humans also seeks out ACE2.

              Existing computer models predicted that the new coronavirus would not bind to ACE2 as well as the SARS virus. However, to their surprise, the researchers found that the spike protein of the new coronavirus actually bound far better than computer predictions, likely because of natural selection on ACE2 that enabled the virus to take advantage of a previously unidentified alternate binding site. Researchers said this provides strong evidence that that new virus was not the product of purposeful manipulation in a lab. In fact, any bioengineer trying to design a coronavirus that threatened human health probably would never have chosen this particular conformation for a spike protein.

              The researchers went on to analyze genomic data related to the overall molecular structure, or backbone, of the new coronavirus. Their analysis showed that the backbone of the new coronavirus’s genome most closely resembles that of a bat coronavirus discovered after the COVID-19 pandemic began. However, the region that binds ACE2 resembles a novel virus found in pangolins, a strange-looking animal sometimes called a scaly anteater. This provides additional evidence that the coronavirus that causes COVID-19 almost certainly originated in nature. If the new coronavirus had been manufactured in a lab, scientists most likely would have used the backbones of coronaviruses already known to cause serious diseases in humans.

              So, what is the natural origin of the novel coronavirus responsible for the COVID-19 pandemic? The researchers don’t yet have a precise answer. But they do offer two possible scenarios.

              In the first scenario, as the new coronavirus evolved in its natural hosts, possibly bats or pangolins, its spike proteins mutated to bind to molecules similar in structure to the human ACE2 protein, thereby enabling it to infect human cells. This scenario seems to fit other recent outbreaks of coronavirus-caused disease in humans, such as SARS, which arose from cat-like civets and Middle East respiratory syndrome (MERS), which arose from camels.

              The second scenario is that the new coronavirus crossed from animals into humans before it became capable of causing human disease. Then, as a result of gradual evolutionary changes over years or perhaps decades, the virus eventually gained the ability to spread from human-to-human and cause serious, often life-threatening disease.

              Either way, this study leaves little room to refute a natural origin for COVID-19. And that’s a good thing because it helps us keep focused on what really matters: observing good hygiene, practicing social distancing, and supporting the efforts of all the dedicated health-care professionals and researchers who are working so hard to address this major public health challenge.

              Finally, next time you come across something about COVID-19 online that disturbs or puzzles you, I suggest going to FEMA’s new Coronavirus Rumor Control web site. It may not have all the answers to your questions, but it’s definitely a step in the right direction in helping to distinguish rumors from facts.

              Reference:
              [1] The proximal origin of SARS-CoV-2. Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. Nat Med, 17 March 2020. [Epub ahead of publication]

              COVID-19, MERS & SARS (National Institute of Allergy and Infectious Diseases/NIH)

              Andersen Lab (Scripps Research Institute, La Jolla, CA)

              Robert Garry (Tulane University School of Medicine, New Orleans)

              NIH Support: National Institute of Allergy and Infectious Diseases National Human Genome Research Institute


              Impact of Host Genomics on COVID-19: What We Know and Don’t Know

              Both pathogen and host factors affect susceptibility and progression to infectious diseases. The host genome influences innate and adaptive immunity and can explain some of the differences in risk and severity of disease among those exposed to the same pathogen. The current COVID-19 pandemic raises these same pressing questions: Why does exposure to the same SARS-CoV-2 virus result in a range of disease outcomes, from asymptomatic infections to severe disease requiring mechanical ventilation to death? Why are we observing morbidity and mortality in some young persons without the hallmark comorbidities previously observed with severe disease?

              One factor that may explain this remarkable range of outcomes is host genomics. Gaining better insight into and understanding of underlying biology can aid the identification of therapeutic targets.

              Dr. Duggal will discuss what we know and don&rsquot know about the role of host genomics in COVID-19 and other coronaviruses, as well as ongoing initiatives and studies that are seeking to assess the role of host genomics in COVID-19. She will also discuss the potential public health impact of host genomics in COVID-19 and the importance of sound epidemiological study designs.


              Potential Benefits of Host Genomic Investigations

              In the decade following the SARS outbreak in 2003, several human candidate gene studies of infection susceptibility and severity were conducted. Human genome-wide association studies (GWAS) were proposed as a way to investigate the “super-spreader” phenomenon observed in the SARS and MERS outbreaks. Human genetic factors have also been investigated in avian and swine influenza outbreaks, for example in studies of family clustering of H5N1 and pediatric morbidity following H1N1 infection.

              Although priority for such research efforts can taper without a sustained commitment, an integrated approach to “research preparedness” includes actions before, during, and after the event. Advances in technology now make it possible to analyze host genomic factors while an outbreak is underway. The ability to quickly and accurately identify vulnerable and protective host factors could expand the effectiveness of the public health approach to COVID-19.

              Genome sequencing technologies that identified the SARS coronavirus in 2003 have evolved rapidly in the past two decades. Chinese scientists were able to sequence COVID-19 and post the results online within two weeks of the first reported cases. Research priorities in the current outbreak include devising rapidly deployable diagnostic tests, better understanding transmission, developing and testing antiviral drugs, and ultimately, developing a protective vaccine.

              Both viral and human genomic information may be important for achieving these goals. Finding biological mechanisms for severe infection could inform the development of therapeutics targeting those pathways. Information on human genetic variants associated with susceptibility to severe infection could be useful for prevention within families and healthcare workers or for directing clinical care on hospital admission.

              Research publications have suggested the potential for ACE2 genetic variants, interleukin-6, HLA antigens, and blood groups to be risk factors in COVID-19 severity and outcomes. Am emerging global COVID-19 host genetics initiative is bringing together the human genetics community “to generate, share and analyze data to learn the genetic determinants of COVID-19 susceptibility, severity and outcomes. Such discoveries could help to generate hypotheses for drug repurposing, identify individuals at unusually high or low risk, and contribute to global knowledge of the biology of SARS-CoV-2 infection and disease severity.”

              Ideally, scientific studies of COVID-19 risk factors for transmission and severity should include both viral and human genomes and the interaction of these two genomes, along with other traditional environmental, social and economic factors, and emerging types of “big data”. Together, such studies could not only accelerate our knowledge base but contribute to a new era of precision public health.

              One comment on &ldquoThe Public Health Impact of COVID-19: Why Host Genomics?&rdquo

              Comments listed below are posted by individuals not associated with CDC, unless otherwise stated. These comments do not represent the official views of CDC, and CDC does not guarantee that any information posted by individuals on this site is correct, and disclaims any liability for any loss or damage resulting from reliance on any such information. Read more about our comment policy ».


              Contents

              The Institute has two campuses in Delhi. The North Campus is the older of the two campuses and is in the campus of Delhi University, on Mall Road opposite to Jubilee Hall. The new campus is in South Delhi, on Mathura Road at Sukhdev Vihar.

              IGIB was established in 1977 as the Center for Biochemical Technology (CBT). The Functional Genomics Unit was established in 1998 with the focus shifting from chemical to genomics research. The institute was renamed "Institute of Genomics and Integrative Biology" in 2002.

              In 2009, a team at the institute sequenced the genome of the wild-type zebrafish, with about 1.7 billion base pairs. This made the fish, which is native to the Himalayan region, the first vertebrate to have its whole genome sequenced in India, as previously Indian scientists had only sequenced bacteria and plant genomes. [2] [3]

              In December 2009, scientists at IGIB performed the first re-sequencing of a human genome in India. [4] [5] [6] The Institute also collaborated on decoding the first Sri Lankan [7] [8] genome and Malaysian genome. [9] The Institute is also a member of the Open Personal Genomics Consortium. [10]

              COVID-19 pandemic Edit

              Researchers at the institute reported the first high-throughput [11] next-generation sequencing based approach for detection and genetic epidemiology of SARS-CoV-2. [12] This approach has been extensively used to understand the genetic epidemiology of SARS-CoV-2 in the state of Kerala, [13] which has significantly influenced policy and preparedness [14] in the state to curb the spread of the epidemic as well as implementation of evidence based policies. [15]

              Researchers at the institute also reported the first cases of COVID-19 reinfection in the country [16] apart from identifying a novel clade of SARS-CoV-2 in India named I/A3i. [17] Researchers at the institute also discovered an emerging lineage with N440K mutation in spike protein associated with immune escape. [18] [19] A comprehensive suite for computational resources to understand the genomes and genetic epidemiology of SARS-CoV-2 has been maintained. [20] One of the first genetically characterized cases of COVID-19 vaccine breakthrough infections was reported by the institute [21]

              Researchers at CSIR-IGIB also developed the test called FELUDA based on CRISPR gene editing which is highly efficient and fast to combat the testing capacity of the country and has been approved by Drugs Controller General of India. The test has been licensed to Tata Group for commercial production. [22]

              The institute has initiated a unique programme to use cutting-edge genomic technologies to understand Rare genetic diseases in India and pioneering the application of genomics for Precision Medicine in clinics. One of the programmes which has been initiated on this front is Genomics for Understanding Rare Disease, India Alliance Network (GUaRDIAN). [23] GUaRDIAN is a large-scale collaborative network of clinicians from around India trying to use genomics in clinical practice, with the focused aim to understand genetic structure of rare genetic diseases in India. [24]

              The consortium aims at using cutting-edge genomics technology to enable identification of genetic variations in diseases and enable clinicians arrive at precise diagnosis for rare genetic disease. Apart from working closely with clinicians, the consortium aims to foster education, awareness and the widespread adoption of genomic technology in clinical settings, in addition to creating and disseminating the highest standards of genomic data generation and interpretation in India. [25]

              In the few years, it has been able to work closely with clinicians in the network to be able to offer proof of principles for the application of Genomics for Precision Medicine. [26] [27] [28] A comprehensive programme for patient referral is also functional. [29]

              The IndiGen programme on Public Health Genomics [30] aims to undertake whole genome sequencing of 1000 Indian individuals representing diverse ethnic groups from India. The data generated as part of IndiGen would provide the baseline for allele frequencies of genetic variants for genetic epidemiology and aid policy decisions. The frequencies of clinically relevant genetic variants would form the template for enabling diagnostic approaches for prevalent genetic diseases and also for optimising therapies through pharmacogenomics. A comprehensive resource providing searchable access to the data is also made available [31]

              The main IGIB campus is located at Mall Road, New Delhi near Delhi University North Campus. IGIB's alliance with the Biotech/Pharmaceuticals has led to its growth and setting up of two extension centers - one at South Delhi (IGIB Annex at TCGA, Okhla) and the other at Western Delhi at Naraina.

              IGIB was a co-host of the 13th meeting of the Human Genome Organization (HUGO) in 2008, held at Hyderabad International Convention Centre. [32]


              Genetic correlations

              We used a high-definition likelihood method 25 to provide an initial estimate of heritability based on single-nucleotide polymorphisms (SNPs) (that is, the proportion of phenotypic variance captured by additive effects at common SNPs) for severe COVID-19, which was found to be 0.065 (s.e. = 0.019). We were not able to detect a significant signal for heritability in two additional analyses: first, using controls from the 100,000 Genomes Project (in which matching to the cases from GenOMICC is less close, which may limit heritability estimation) and second, in a smaller GWAS in which some cases from GenOMICC were compared with controls from the UK Biobank, using matched data for body-mass index and age where possible. This second analysis was less powerful because of the lack of close matches for many cases (n = 1,260 cases, n = 6300 controls) (Supplementary Fig. 14). Including rare variants in future analyses, which have larger numbers of cases of COVID-19, will provide a more comprehensive estimate of heritability. We also tested for genetic correlations with other traits—that is, the degree to which the underlying genetic components are shared with severe COVID-19. Using the high-definition likelihood method, we identified significant negative genetic correlations with educational attainment and intelligence. Significant positive genetic correlations were detected for a number of adiposity phenotypes including body-mass index and leg fat (Supplementary Fig. 19).

              Consistent with GWAS results from other infectious and inflammatory diseases, there was a significant enrichment of strongly associated variants in promoters and enhancers 26 , particularly those identified by the EXaC study as under strong evolutionary selection 27 (Supplementary Fig. 18). The strongest tissue-type enrichment was in spleen (which may reflect enrichment in immune cells), followed by pancreas (Supplementary Fig. 20).


              19: Genomics - Biology

              National Institutes of Health (NIH)

              National Human Genome Research Institute (NHGRI)
              National Institute of Dental and Craniofacial Research (NIDCR)

              Initiative to Maximize Research Education in Genomics: Diversity Action Plan (R25)

              • March 10, 2020 - Reminder: FORMS-F Grant Application Forms & Instructions Must be Used for Due Dates On or After May 25, 2020- New Grant Application Instructions Now Available. See Notice NOT-OD-20-077.
              • November 22, 2019 - Notice of NIH's Interest in Diversity. See Notice NOT-OD-20-031.
              • November 6, 2019 - Notice of NIDCR Participation in PAR-19-380. See Notice NOT-DE-19-019.

              NOT-OD-19-128, Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research.

              NOT-OD-19-137, Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research.

              NOT-OD-19-109 , Requirement for ORCID iDs for Individuals Supported by Research Training, Fellowship, Research Education, and Career Development Awards Beginning in FY 2020

              The NIH Research Education Program (R25) supports research education activities in the mission areas of the NIH. The overarching goal of this NHGRI Diversity Action Plan (DAP) R25 program is to support educational activities that enhance the diversity of the biomedical, behavioral, social and clinical research workforce in genomics. This funding opportunity announcement seeks to expose students at the undergraduate, post-baccalaureate and graduate levels who are from diverse backgrounds, including those from underrepresented groups, to the foundational sciences relevant to genomics to enable them to pursue careers that span all areas of interest to NHGRI - genome sciences, genomic medicine and genomics and society. For the purposes of this FOA, the term “genomics” encompasses issues and activities in these three areas.

              To accomplish the stated over-arching goal, this FOA will support creative educational activities with a primary focus on Research Experiences during either the summer or academic year. The research experiences must be based on the foundational sciences relevant to genomics: genomic sciences (e.g. technology development, data science) genomic medicine (e.g. epidemiology, pharmacogenomics, clinical implementation) and genomics and society (e.g. bioethics, social and behavioral sciences, law, the humanities). A secondary focus is on Courses for Skills Development. Complementary didactic activities are encouraged, especially those academic courses that have the potential to increase opportunities for success at the next career level. The proposed research education programs must include both courses for skills development and research experiences with primary emphasis on research experiences. Proposed courses should be developed in conjunction with and support research experiences to enhance skills development.

              30 days before application due date

              January 25, 2020, January 25, 2021, January 25, 2022 (new, renewal, revision applications) January 25, May 25, or Sept 25 of years 2020, 2021, 2022 (resubmission applications).

              All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

              Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

              It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

              Applications that do not comply with these instructions will not be reviewed

              There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

              1. Use the NIH ASSIST system to prepare, submit and track your application online.
              2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

              The NIH Research Education Program (R25) supports research educational activities that complement other formal training programs in the mission areas of the NIH Institutes and Centers. The overarching goals of the NIH R25 program are to: (1) complement and/or enhance the training of a workforce to meet the nation’s biomedical, behavioral and clinical research needs (2) encourage individuals from diverse backgrounds, including those from groups underrepresented in the biomedical and behavioral sciences, to pursue further studies or careers in research (3) help recruit individuals with specific specialty or disciplinary backgrounds to research careers in biomedical, behavioral and clinical sciences and (4) foster a better understanding of biomedical, behavioral and clinical research and its implications.

              The over-arching goal of this NHGRI R25 program is to support educational activities that enhance the diversity of the biomedical, behavioral, social, computational and clinical research workforce in genomics. The DAP Program seeks to expose students at the undergraduate, post-baccalaureate and graduate levels who are from diverse backgrounds, including those from underrepresented groups, to the foundational sciences relevant to genomics to enable them to pursue careers that span all areas of interest to NHGRI - genome sciences, genomic medicine and genomics and society.

              To accomplish the stated over-arching goal, this FOA will support creative educational activities with a focus on:

              • Research Experiences:(primary focus) based on the foundational sciences relevant to genomics: genomic sciences (e.g. technology development, data science) genomic medicine (e.g. epidemiology, pharmacogenomics, clinical implementation) and genomics and society (e.g. bioethics, social and behavioral sciences, law, the humanities). Experiences can take place during the academic school year or as summer programs.
              • Courses for Skills Development:(secondary focus) complementary didactic activities are encouraged, especially those academic courses that have the potential to increase opportunities for success at the next career level. The field of genomics is data driven. Courses that introduce participants to fundamental knowledge in data sciences, such as bioinformatics, machine learning, statistics, etc., are especially encouraged.

              The NIH is committed to enhancing the diversity of their workforce. (Valantine and Collins, “National Institutes of Health addresses the science of diversity” Proc. Natl Acad Sci USA 112, 12240 (2015)). Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the researchers, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust.

              The National Human Genome Research Institute (NHGRI) is committed to enhancing the pool of individuals from diverse backgrounds who have the training to pursue careers in genome sciences, genomic medicine, and genomics and society research. Genome sciences and genomic medicine research offer tremendous opportunities for improving human health, and genomics and society research offers the chance to not only improve human health, but also to explore some of the most profound ethical, legal and social issues of our time. NHGRI wants the best minds to engage in this research. There are extraordinary career opportunities in genome sciences, genomic medicine, and genomics and society research in which all should have an opportunity to participate. The very nature of research demands a diversity of viewpoints and scientific interests. A major emphasis of this research will be the development of: resources and methods and technologies that will accelerate research in understanding the structure of genomes understanding the biology of genomes understanding the biology of disease advancing the science of medicine and improving the effectiveness of healthcare. The significant societal ramifications of this research will also need to be addressed. It is clearly desirable to have individuals involved who bring diverse perspectives to this research, including an interest in understanding diseases that disproportionately affect some populations. Genome sciences, genomic medicine, and genomics and society research will affect all populations and thus all groups need to participate in setting the research agenda and examining the broader issues raised by it.

              NIH's ability to help ensure that the nation remains a global leader in scientific discovery and innovation is dependent upon a pool of highly talented scientists from diverse backgrounds who will help to further NIH's mission. However, despite advancements in scientific research, some populations have not had access to cutting-edge research and training opportunities, and do not participate fully in the biomedical sciences research workforce. These underrepresented groups include individuals from underrepresented racial and ethnic groups, individuals with disabilities, and individuals from disadvantaged backgrounds, as described in NOT-OD-18-210.

              The overall objective of the DAP Program is to support a diverse pool of undergraduates, post-baccalaureates and graduate students, including those from underrepresented groups, to help them successfully transition to the next stage of their research career in a genomics-related field. Recent studies have highlighted the importance of including diverse and under-represented individuals in human genomics research and the striking gaps in attaining that inclusion. The National Human Genome Research Institute is committed to establishing foundational approaches to study the role of genomic variation in health and disease that include diverse populations. Supporting efforts to diversify the genomics workforce serves as an effective strategy for increasing diversity in genomic research studies. (Hindorff et al. “Prioritizing diversity in human genomics research” Nat Rev Genetics 19, 175 (2018)).

              Programmatic Approach

              As a leading authority in the field of genomics, NHGRI’s mission is to accelerate scientific and medical breakthroughs that improve human health and well-being. We do this by driving cutting-edge research, developing new technologies, and studying the impact of genomics on society. This requires expertise in the foundational sciences relevant to genomics--biomedical, physical, mathematical, and computer and engineering sciences, biostatistics, epidemiology, bioinformatics, bioethics, social and behavioral sciences, law, and the humanities. Thus, research education in these areas will allow those who participate in NHGRI-supported research activities to be well positioned to contribute to biomedical research in the future.

              It is assumed that the institutions that apply for this award will:

              - have faculty with broad experiences in one or more of the three areas of genomics relevant to NHGRI: genomic sciences, genomic medicine or genomics and society

              - have experienced mentors who have worked with underrepresented individuals in traditional NIH training programs and

              - be able to demonstrate that related research education or training programs at their institution will work collaboratively with the Diversity Action Plan (DAP) program to ensure a smooth transition of DAP participants to the next career phase.

              The guiding principles of what can be supported under this funding opportunity announcement are that participants:

              - should be exposed to appropriate didactic training in the foundational disciplines of genomics in order to develop critical thinking skills as appropriate for their career level and research focus

              - should receive research experiences that do not focus on any particular disease or groups of diseases but skills and knowledge that are generally applicable to a variety of biomedical research questions

              - must be so prepared that they can use this knowledge and these experiences to move to the next stage of their career and

              - must be in a research environment where they will have an opportunity to select from a variety of genomic research experiences and mentors.

              The types of research experiences that can be supported under this award include:

              -summer or semester research experiences and courses for skills development for undergraduate students with the objective of pursuing a doctoral degree in one of the foundational sciences relevant to genomics

              - up to two years of part-time support for post baccalaureate research and courses for skills development with the objective of transitioning to graduate school participants may take academic courses, but may not be enrolled in a formal graduate program and

              - up to two years part-time support for graduate students with the objective of transitioning to an F31 or other source of peer-reviewed support.

              The duration of the research experiences, the transition of participants to individual support mechanisms, and their transition to the next career stage are important considerations in DAP programs. PDs/PIs should limit participant selection to eligible individuals who are committed to a research career.

              The career outcome goal for individuals supported by DAP programs is to remain in genomics-related research. This will include both research-intensive careers in academia and industry and research-related careers in various sectors, e.g., academic institutions, government agencies, for-profit businesses, and private foundations. DAP programs should make available structured, career development mentoring and learning opportunities (e.g., workshops, discussions, Individual Development Plans) to provide participants knowledge of various potential career directions and the steps needed to transition to the next stage of their chosen career.

              See Section VIII. Other Information for award authorities and regulations.

              Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

              New
              Renewal
              Resubmission
              Revision

              The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

              Not Allowed: Only accepting applications that do not propose clinical trial(s)

              Note: Appointed Participants are permitted to obtain research experience in a clinical trial led by a mentor or co-mentor.

              The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

              Application budgets are limited to $300,000 direct costs per year.

              The total project period may not exceed 5 years.

              Individuals designing, directing, and implementing the research education program may request salary and fringe benefits appropriate for the person months devoted to the program. Salaries requested may not exceed the levels commensurate with the institution's policy for similar positions and may not exceed the congressionally mandated cap. (If mentoring interactions and other activities with participants are considered a regular part of an individual's academic duties, then any costs associated with the mentoring and other interactions with participants are not allowable costs from grant funds). Personnel costs must be directly associated with the program and should be well-justified, reasonable, and may not exceed 30% of the total direct costs in any year of the project period.

              Items that may NOT be supported with DAP funds include:

              -Salaries and fringe benefits for the program faculty

              -Salary and support for central institutional administrative personnel (e.g., budget officers, grant assistants, and building maintenance personnel), which are usually paid from institutional overhead charges

              -Salary and support for administrative activities such as institutional public relations or health and educational services.

              Participants (recipients of the research experiences) may be paid through salary and fringe benefits if specifically required for the proposed research education program and sufficiently justified. Participant costs must be itemized in the proposed budget.

              Allowable participant costs depend on the educational level/career status of the individuals to be selected to participate in the program.

              While generally not an allowable cost, with strong justification, participants in the research education program may receive per diem unless such costs are furnished as part of the registration fee.

              Individuals supported by NIH training and career development mechanisms (K, T, or F awards) may receive, and indeed are encouraged to receive, educational experiences supported by an R25 program, as participants, but may not receive salary or stipend supplementation from a research education program.

              Because the R25 program is not intended as a substitute for an NRSA institutional training program (e.g.,T32), costs to support full-time participants (supported for 40 hours/week for a continuous, 12-month period) are not allowable.

              TUITION REMISSION: For post-baccalaureates, tuition remission for a course deemed necessary to enhance the academic preparedness for graduate studies may be requested. Tuition remission must be specifically justified and may not exceed the in-state tuition cost at institutions that also have out-of-state tuition charges.

              TRAVEL: Participants are strongly encouraged to attend at least one NHGRI Research Training and Career Development Annual Meeting while supported on this program. Travel costs may be requested to attend this meeting. If this is requested, then travel costs to attend a second scientific meeting may also be requested. For postbaccalaureate and summer programs, funds may be requested to cover the costs of travel between the place of residence and the training institution.

              HOUSING – For summer programs, support may be requested to augment the cost of housing at the program site. Contributions to, or coverage of, housing by the institution should be addressed in the Institutional Environment and Commitment section of the application.

              Consultant costs, program evaluator costs, supplies, promotional materials, academic courses, recruitment travel, NHGRI training meeting travel may be included in the proposed budget. These expenses must be justified as specifically required by the proposed program and must not duplicate items generally available at the applicant institution. All other expenses are not allowed.

              Program evaluation costs are limited to $5,000 per year.

              Recruitment travel costs are limited to $3,000 per year.

              PI/PD and key staff are expected annually to attend the NHGRI Research Training and Career Development Meeting travel funds should be requested.

              Total expenses in this category may not exceed 10% of the total direct costs in any year of the project period.

              Indirect Costs (also known as Facilities & Administrative [F&A] Costs) are reimbursed at 8% of modified total direct costs (exclusive of tuition and fees and expenditures for equipment), rather than on the basis of a negotiated rate agreement.

              NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

              Higher Education Institutions

              • Public/State Controlled Institutions of Higher Education
              • Private Institutions of Higher Education

              The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

              • · Hispanic-Serving Institutions
              • · Historically Black Colleges and Universities (HBCUs)
              • · Tribally Controlled Colleges and Universities (TCCUs)
              • · Alaska Native and Native Hawaiian Serving Institutions
              • · Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

              Nonprofits Other Than Institutions of Higher Education

              • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
              • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

              The sponsoring institution must assure support for the proposed program. Appropriate institutional commitment to the program includes the provision of adequate staff, facilities, and educational resources that can contribute to the planned program.

              Institutions with existing Ruth L. Kirschstein National Research Service Award (NRSA) institutional training grants (e.g., T32) or other Federally funded training programs may apply for a research education grant provided that the proposed educational experiences are distinct from those training programs receiving federal support. In many cases, it is anticipated that the proposed research education program will complement ongoing research training occurring at the applicant institution.

              Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
              Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
              Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

              Applicant Organizations

              Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

              • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application. – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
              • · NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

              Program Directors/Principal Investigators (PD(s)/PI(s))

              All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

              Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support.

              For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

              The PD/PI should be an established investigator in the scientific area in which the application is targeted and capable of providing both administrative and scientific leadership to the development and implementation of the proposed program. The PD/PI will be expected to monitor and assess the program and submit all documents and reports as required.

              The PD/PI must have significant research funding from NIH (e.g. multiple research grants, a large center grant, or cooperative agreement, etc.) in at least one of the areas relevant to NHGRI's research programs - genome sciences, genomic medicine and genomics and society research.

              This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

              Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

              The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

              • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
              • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
              • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

              Only one award will be made per institution for activities that focus in one of three areas - genome sciences, genomic medicine and genomics and society. Institutions that already have an award in one of these three areas are not eligible to apply for an award in the same area, but can apply for an award in a different area. Institutions that have more than one NHGRI-supported R25 diversity program and/or T32 program must demonstrate coordination and collaboration such that there is synergy amongst the programs.

              Researchers from diverse backgrounds, including racial and ethnic minorities, persons with disabilities, and women, are encouraged to participate as preceptors/mentors. Mentors should have research expertise and experience relevant to the proposed program. Mentors must be committed to continue their involvement throughout the total period of the mentee’s participation in this award.

              Because participants are expected to have the opportunity to pursue their research and educational experiences focused on a variety of genomic research topics, it is expected that the program faculty will have significant research programs in one or more of the three research areas relevant to genomics.

              NIH encourages institutions to diversify their student and faculty populations to enhance the participation of individuals from groups identified as underrepresented in the biomedical, clinical, behavioral and social sciences, as described in the Notice of NIH’s Interest in Diversity, NOT-OD-18-210.

              Participants from engineering, mathematics, computer science, physics, chemistry, biology, biostatistics, bioinformatics, bioethics, social and behavioral sciences, law, and the humanities, and other relevant science programs who have an interest in the genomics should be encouraged to participate in the program.

              Unless strongly justified on the basis of exceptional relevance to NIH, research education programs should be used primarily for the education of U.S. citizens and permanent residents.

              The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

              It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions will not be reviewed.

              Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

              By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

              • Descriptive title of proposed activity
              • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
              • Names of other key personnel
              • Participating institution(s)
              • Number and title of this funding opportunity

              The letter of intent should be sent to:

              Tina Gatlin, Ph.D.
              National Human Genome Research Institute, NIH
              Telephone: 301-480-2280
              Email: [email protected]

              All page limitations described in the SF424 (R&R) Application Guide and the Table of Page Limits must be followed.

              Instructions for Application Submission

              The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

              Follow all instructions provided in the SF424 (R&R) Application Guide.

              Follow all instructions provided in the SF424 (R&R) Application Guide.

              Follow all instructions provided in the SF424 (R&R) Application Guide with the following additional modifications:

              Facilities & Other Resources. Describe the educational environment, including the facilities, laboratories, participating departments, computer services, and any other resources to be used in the development and implementation of the proposed program. List all thematically related sources of support for research training and education following the format for Current and Pending Support.

              Advisory Committee (1-page maximum): Provide a plan for the appointment of an Advisory Committee to monitor progress of the research education program. The composition, roles, responsibilities, and desired expertise of committee members, frequency of committee meetings, and other relevant information should be included. Describe how the Advisory Committee will evaluate the overall effectiveness of the program. Advisory Committee members should only be named in the application if they have been invited to participate at the time the application is submitted. Renewal applications with Advisory Committees should include the names of all committee members during the past project period. Please name your file “Advisory_Committee.pdf”

              Tables. The DAP is an institutional program and as such applicants must provide details about the institution and its setting using Data Tables 2, 4, 8A, and 8D (http://grants.nih.gov/grants/funding/424/datatables.htm).


              The following Tables are required for new applications:
              Training Table 2. Participating Faculty Members, Undergraduate and/or Predoctoral Training Table, as applicable (Programs that include post-baccalaureate participants should include information on faculty mentoring of post-baccalaureates on the Undergraduate Training Table.)
              Training Table 4. Research Support of Participating Faculty Members

              The following Tables are required for renewal applications:
              Training Table 2. Participating Faculty Members, Undergraduate and/or Predoctoral Training Table, as applicable (Programs that include post-baccalaureate participants should include information on faculty mentoring of post-baccalaureates on the Undergraduate Training Table.)
              Training Table 4. Research Support of Participating Faculty Members

              Training Table 8A (Part I only) Program Outcomes: Predoctoral (for graduate students)
              Training Table 8D (Part I only). Program Outcomes: Undergraduate (for postbaccalaureate and undergraduate students)

              Please name your files "Table 2-Undergraduate.pdf", "Table 2-Predoctoral.pdf", Table 4.pdf", "Table 8A.pdf", or "Table 8D.pdf" as appropriate.

              The filename provided for each “Other Attachment” will be the name used for the bookmark in the electronic application in eRA Commons.

              Follow all instructions provided in the SF424 (R&R) Application Guide.

              Follow all instructions provided in the SF424 (R&R) Application Guide with the following additional modifications:

              • Include all personnel other than the PD(s)/PI(s) in the Other Personnel section, including clerical and administrative staff.
              • Use Section A and B for Personnel Costs.
              • Use Section E for Participant Support Costs to include all allowable categories of funds requested to support participants in the program, including participant travel.
              • For Other Program-Related Expenses, use Sections D (PI/staff travel) and F (other costs).
              • Program coordinators are allowed as long as their roles in the program implementation are clearly defined and significantly different from the roles of the PDs/PIs. The duties and responsibilities of the program coordinators must be well described in the budget and must include a strong justification. The number of person months must be strongly justified in relation to the number of program participants.
              • Costs of consultants for evaluation of the program is allowed however, if the evaluator is an employee of the applicant institution, the cost must be included in the category of key personnel salary (effort listed in person months). [Employees cannot be consultants unless it is allowed by institutional policy and the person is consulting in a field distinctly separate from their "normal" field of work.]
              • The total compensation package for participants should be reasonable for the work performed and consistent with the compensation paid to all participants in similar circumstances, regardless of the source of support for the activity.

              The following account summarizes some of the UNALLOWABLE costs under the DAP Program but is not an all-inclusive list. Please see 45 CFR §75, Subpart E "Cost Principles" for a complete list of costs that may be deemed unallowable under this program:

              • Undergraduate and graduate student tuition, housing, or food, during the academic year.
              • Food and beverage costs (NOTE: Travel per diem costs provided in accordance with an institution's written travel policies to cover incidental meal expenses is permissible).
              • Foreign travel.
              • Student support in the form of a “stipend” (note: “stipend” differs technically from “salary/wages” which is allowable. See: https://grants.nih.gov/grants/policy/nihgps/nihgps.pdf).
              • Costs for textbooks, laptops, incentives, memberships, or subscriptions to internet services or journals.
              • Support for faculty research (all faculty mentors are expected to have their own research support).
              • Equipment.
              • Costs of workshops or courses with a limited focus such as preparation for a specific test, (i.e., GRE and MCAT costs are not allowable).
              • Alterations and renovations.
              • Consortium/contractual arrangements.

              Follow all instructions provided in the SF424 (R&R) Application Guide

              All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

              The Research Strategy section must be used to upload the Research Education Program Plan, which must include the following components described below:

              • · Proposed Research Education Program
              • · Program Director/Principal Investigator
              • · Program Faculty
              • · Program Participants
              • · Institutional Environment and Commitment
              • · Diversity Recruitment Plan
              • · Plan for Instruction in the Responsible Conduct of Research
              • · Evaluation Plan
              • · Dissemination Plan

              Research Education Program Plan

              Proposed Research Education Program. While the proposed research education program may complement ongoing research training and education occurring at the applicant institution, the proposed educational experiences must be distinct from those research training and research education programs currently receiving federal support. When research training programs are on-going in the same department, the applicant organization should clearly distinguish between the activities in the proposed research education program and the research training supported by the training program.

              Explain the basis and rationale for the program and any educational principles or evidence of past success that it may be based on.

              Provide programmatic detail and rationale for the proposed research experiences and courses for skills development and describe how these activities address the needs of the diverse program participants.

              Describe how each proposed activity will contribute toward realization of the specific aims.

              Describe the milestones and benchmarks (i.e., anticipated intermediate steps toward the objectives).

              Discuss any perceived impediments to implementing the proposed activities and alternative strategies to achieve the measurable objectives.

              Provide concise information on the selection and retention process for the participants in the DAP program, including the criteria related to the students’ academic status, participants’ research education and training progress, and role of the faculty/personnel involved.

              Describe how experiences during the summer and/or academic year will contribute toward measurable objectives and student development. Demonstrate that participants will have authentic, meaningful research experiences in the laboratories or research groups of extramurally-funded investigators who are actively engaged in genomics-related research.

              Describe how the students will be exposed to research projects that will give them the foundational knowledge and skills that can be applied to a broader range of genomic problems.

              Describe how the PD/PI will specifically interact with program faculty with the goal of preparing students to move successfully to the next career level.

              Describe how the PD/PI and program program coordinator will specifically interact, and how the program coordinator will be integrated with the program faculty to facilitate the program.

              If applicable, describe how the applicant will coordinate and collaborate with other NHGRI-supported R25 diversity and/or T32 programs to provide synergy amongst the programs.

              For renewal applications, describe how this plan resulted in getting participants to their next career level. Special attention should be paid to unique aspects of the plan that resulted in successful outcomes.

              For renewal applications, provide information on outcomes of past participants in the program, including, but not limited to, counts (numbers and percentages of participants) and summaries of the following:

              • Participants who completed the DAP program (alumni)
              • Participants who applied for admission to an academic program at their next career level
              • Participants who enrolled in an academic program at their next career level
              • Participants who completed an academic program at their next career level
              • Participants who are employed in a tenure-track faculty position
              • Participants who are employed in research-related positions
              • Participants who are employed in non-research related positions.

              Program Director/Principal Investigator. Describe arrangements for administration of the program. Provide evidence that the Program Director/Principal Investigator is actively engaged in research and/or teaching in an area related to the mission of NIH, and can organize, administer, monitor, and evaluate the research education program. For programs proposing multiple PDs/PIs, describe the complementary and integrated expertise of the PDs/PIs their leadership approach, and governance appropriate for the planned project.

              The PD/PI assumes responsibility for the overall execution of the DAP Program and is typically responsible for placement of students in research laboratories and coordination and implementation of developmental education and mentoring activities across the different participating institutions. Describe how the PD(s)/PI(s) will work with the program coordinator and program faculty to monitor and evaluate the progress of the individual program elements and the overall functioning of the program.

              The PD/DI must have significant expertise in the foundational sciences relevant to NHGRI programs (genome sciences, genomic medicine and/or genomics and society), experience relevant to the proposed diversity program, and a history of mentoring diverse students.

              Program Faculty. Researchers from diverse backgrounds, including racial and ethnic minorities, persons with disabilities, and women, are encouraged to participate as program faculty. Faculty should have research expertise and experience relevant to the proposed program and demonstrate a history of, or the potential for, their intended roles.

              Program Participants. Applications must describe the intended participants, and the eligibility criteria and/or specific educational background characteristics that are essential for participation in the proposed research education program. Identify the career levels for which the proposed program is planned. Institutions are encouraged to consider whether the proposed participants would help achieve the overall goals of this NHGRI Diversity Action Plan R25 Program.

              • Include a description (including size) of the potential applicant pool from the participating institutions based on the selection criteria established for the proposed DAP program
              • Describe the process for selection of the program-supported participants (examples of accepted indicators include, but are not limited to, previous academic success, practical research experience, written statements that express interest and commitment and letters of recommendations from faculty, research supervisors and/or other community leaders that speak to the applicant’s merit and interest in genomics research)
              • Describe the retention strategies and follow-up activities that would ensure students remain engaged and are receiving high quality mentorship and guidance within the program.

              Institutional Environment and Commitment. Describe the institutional environment, reiterating the availability of facilities and educational resources (described separately under “Facilities & Other Resources”), that can contribute to the planned Research Education Program. Evidence of institutional commitment to the research educational program is required. A letter of institutional commitment must be attached as part of Letters of Support (see below). Appropriate institutional commitment should include the provision of adequate staff, facilities, and educational resources that can contribute to the planned research education program.

              Provide evidence that for the duration of this grant the institution will have a significant number of peer-reviewed research projects, (e.g. multiple research grants, a large center grant, or cooperative agreement, etc.) in one or more of the following areas: genome sciences, genomic medicine and genomics and society, in order to provide participants with a variety of experiences. Demonstrate that research and educational experiences will focus on the relevance of the foundational genomic disciplines to the research and not focus on particular disease(s) or health conditions.

              Recruitment Plan to Enhance Diversity (NOT-OD-18-210): Every facet of the United States scientific research enterprise—from basic laboratory research to clinical and translational research to policy formation–requires superior intellect, creativity and a wide range of skill sets and viewpoints . NIH’s ability to help ensure that the nation remains a global leader in scientific discovery and innovation is dependent upon a pool of highly talented scientists from diverse backgrounds who will help to further NIH's mission.

              Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the researchers, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust.

              Underrepresented Populations in the U.S. Biomedical, Clinical, Behavioral and Social Sciences Research Enterprise
              In spite of tremendous advancements in scientific research, information, educational and research opportunities are not equally available to all. NIH encourages institutions to diversify their student and faculty populations to enhance the participation of individuals from groups that are underrepresented in the biomedical, clinical, behavioral and social sciences, such as:

              A. Individuals from racial and ethnic groups that have been shown by the National Science Foundation to be underrepresented in health-related sciences on a national basis (see data at http://www.nsf.gov/statistics/showpub.cfm?TopID=2&SubID=27) and the report Women, Minorities, and Persons with Disabilities in Science and Engineering).

              The following racial and ethnic groups have been shown to be underrepresented in biomedical research: Blacks or African Americans, Hispanics or Latinos, American Indians or Alaska Natives, Native Hawaiians and other Pacific Islanders.

              In addition, it is recognized that underrepresentation can vary from setting to setting individuals from racial or ethnic groups that can be demonstrated convincingly to be underrepresented by the grantee institution should be encouraged to participate in this program. For more information on racial and ethnic categories and definitions, see NOT-OD-15-089.

              B. Individuals with disabilities, who are defined as those with a physical or mental impairment that substantially limits one or more major life activities, as described in the Americans with Disabilities Act of 1990, as amended. See NSF data at https://www.nsf.gov/statistics/2017/nsf17310/static/data/tab7-5.pdf

              C. Individuals from disadvantaged backgrounds, defined as:

              1.Individuals who come from a family with an annual income below established low-income thresholds. These thresholds are based on family size, published by the U.S. Bureau of the Census adjusted annually for changes in the Consumer Price Index and adjusted by the Secretary for use in all health professions programs. The Secretary periodically publishes these income levels at http://aspe.hhs.gov/poverty/index.shtml.

              2.Individuals who come from an educational environment such as that found in certain rural or inner-city environments that has demonstrably and directly inhibited the individual from obtaining the knowledge, skills, and abilities necessary to develop and participate in a research career.

              The disadvantaged background category (C1 and C2) refers to the financial and educational background of individuals, particularly before graduating from high school, while residing in the United States

              Literature shows that women from the above backgrounds (categories A, B, and C) face particular challenges at the graduate level and beyond in scientific fields. (See, e.g., Inside the Double Bind, A Synthesis of Empirical Research on Undergraduate and Graduate Women of Color in Science, Technology, Engineering, and Mathematics http://her.hepg.org/content/t022245n7x4752v2/fulltext.pdf).

              New applications must include a description of plans to enhance recruitment, including the strategies that will be used to enhance the recruitment of prospective trainees from underrepresented backgrounds and may wish to include data in support of past accomplishments.

              Renewal applications must include a detailed account of experiences in recruiting individuals from underrepresented groups during the previous funding period, including successful and unsuccessful recruitment strategies. Information should be included on how the proposed plan reflects the program’s past experiences in recruiting individuals from underrepresented groups.

              For those individuals who participated in the research education program, the report should include information about the duration of education and aggregate information on the number of individuals who finished the program in good standing. Additional information on the required Recruitment Plan to Enhance Diversity is available at Frequently Asked Questions: Recruitment Plan to Enhance Diversity (Diversity FAQs).

              Applications lacking a diversity recruitment plan will not be reviewed.

              Plan for Instruction in the Responsible Conduct of Research. All applications must include a plan to fulfill NIH requirements for instruction in the Responsible Conduct of Research (RCR). The plan must address the five, required instructional components outlined in the NIH policy: 1) Format - the required format of instruction, i.e., face-to-face lectures, coursework, and/or real-time discussion groups (a plan with only on-line instruction is not acceptable) 2) Subject Matter - the breadth of subject matter, e.g., conflict of interest, authorship, data management, human subjects and animal use, laboratory safety, research misconduct, research ethics 3) Faculty Participation - the role of the program faculty in the instruction 4) Duration of Instruction - the number of contact hours of instruction, taking into consideration the duration of the program and 5) Frequency of Instruction –instruction must occur during each career stage and at least once every four years. See also NOT-OD-10-019. The plan should be appropriate and reasonable for the nature and duration of the proposed program. Renewal (Type 2) applications must, in addition, describe any changes in formal instruction over the past project period and plans to address any weaknesses in the current instruction plan. All participating faculty who served as course directors, speakers, lecturers, and/or discussion leaders during the past project period must be named in the application.

              Applications lacking a plan for instruction in responsible conduct of research will not be reviewed.

              Evaluation Plan. Applications must include a plan for tracking the program's participants and evaluating the activities supported by the award. The application must specify baseline metrics (e.g., numbers, educational levels, and demographic characteristics of participants), as well as measures to gauge the short or long-term success of the research education award in achieving its objectives. The plan should address the overall goals and specific measurable objectives that the institution expects to accomplish in preparing students to advance to the next career level in genomics research and in striving to achieve the goals and expectations of the DAP program. Wherever appropriate, applicants are encouraged to obtain feedback from participants to help identify weaknesses and to provide suggestions for improvements.

              Dissemination Plan. A specific plan must be provided to disseminate nationally any findings resulting from or materials developed under the auspices of the research education program, e.g., sharing course curricula and related materials via web postings, presentations at scientific meetings, workshops. Publication of the program's findings and outcomes in peer-reviewed journals is highly encouraged.

              A letter of institutional commitment must be attached as part of Letters of Support (see section above:”Institutional Environment and Commitment.

              Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, , with the following modification:

              When relevant, applications are expected to include a software dissemination plan if support for development, maintenance, or enhancement of software is requested in the application. There is no prescribed single license for software produced. However, the software dissemination plan should address, as appropriate, the following goals:

              • Software source code should be freely available to biomedical researchers and educators in the non-profit sector, such as institutions of education, research institutions, and government laboratories. Users should be permitted to modify the code and share their modifications with others.
              • The terms of software availability should permit the commercialization of enhanced or customized versions of the software, or incorporation of the software or pieces of it into other software packages.
              • To preserve utility to the community, the software should be transferable such that another individual or team can continue development in the event that the original investigators are unwilling or unable to do so.

              Only limited Appendix materials are allowed. Follow the instructions for the Appendix as described in the SF424 (R&R) Application Guide.

              When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

              If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

              Study Record: PHS Human Subjects and Clinical Trials Information

              All instructions in the SF424 (R&R) Application Guide must be followed

              Delayed Onset Study

              Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

              All instructions in the SF424 (R&R) Application Guide must be followed.

              All instructions in the SF424 (R&R) Application Guide must be followed.

              See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

              Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.


              Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.


              Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

              Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

              This initiative is not subject to intergovernmental review.

              All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

              Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

              Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

              Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

              For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

              Important reminders:
              All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

              The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) Application Guide.

              See more tips for avoiding common errors.

              Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

              In order to expedite review, applicants are requested to notify the NHGRI Referral Officer by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD(s)/PI(s) name(s), and title of the application.

              Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

              Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

              For this particular announcement, note the following: The goal of this R25 program is to provide research experiences and education for students at the undergraduate, post baccalaureate and graduate levels from diverse backgrounds, including those from groups underrepresented in scientific disciplines relevant to genomics: genome sciences (e.g. computational biology, quantitative sciences, bioinformatics) genomic medicine (e.g. biostatistics, epidemiology, bioinformatics), and genomics and society (e.g.bioethics, social and behavioral sciences, law, the humanities) to enable them to pursue careers in genomics that span the three areas of interest to NHGRI. The goal of the research experience and courses for skills development are to ensure that participants successfully advance to the next career level in genomics research.

              Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to strongly advance research education by fulfilling the goal of this R25 Education Program, in consideration of the following review criteria and additional review criteria, as applicable for the project proposed.

              Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact.

              Does the proposed program address a key audience and an important aspect or important need in research education? Is there convincing evidence in the application that the proposed program will significantly advance the stated goal of the program?

              Does the DAP application provide a value-added aspect that other student development programs ongoing at the institutions do not provide? Does the research plan show potential to increase the diversity of the biomedical research workforce in the fields of genome sciences, genomic medicine and/or genomics and society?

              Is the PD/PI capable of providing both administrative and scientific leadership to the development and implementation of the proposed program? Is there evidence that an appropriate level of effort will be devoted by the program leadership to ensure the program's intended goal is accomplished? If applicable, is there evidence that the participating faculty have experience in mentoring students and teaching science? If applicable, are the faculty good role models for the participants by nature of their scientific accomplishments? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise are their leadership approach, governance and organizational structure appropriate for the project?

              Will the program faculty collectively provide the expansive type of research and didactic experiences in genomics research so that the experiences received are not focused on any particular disease, diseases or health conditions? Are individuals with the right expertise in the foundational sciences relevant to genome sciences, genomic medicine and/or genomics and society involved in the development and management of the program? Do the PD/PI and key personnel maintain an appropriate level of involvement to ensure the substantial and unique added value critical to research in genome sciences, genomic medicine and/or genomics and society? Does the program coordinator have the expertise to implement activities that are essential for the success of the participants and their anticipated career? Is the program coordinator sufficiently integrated with the PD/PI and with the program faculty participating in the DAP program?

              Taking into consideration the nature of the proposed research education program, does the applicant make a strong case for this program effectively reaching an audience in need of the program’s offerings? Where appropriate, is the proposed program developing or utilizing innovative approaches and latest best practices to improve the knowledge and/or skills of the intended audience?

              For renewal applications, were any innovations implemented by the grantee successful?

              Does the proposed program clearly state its goals and objectives, including the educational level of the audience to be reached, the content to be conveyed, and the intended outcome? Is there evidence that the program is based on a sound rationale, as well as sound educational concepts and principles? Is the plan for evaluation sound and likely to provide information on the effectiveness of the program? If the proposed program will recruit participants, are the planned recruitment, retention, and follow-up (if applicable) activities adequate to ensure a highly qualified participant pool?

              Are the activities commensurate with the program goals? Will the activities facilitate participants moving successfully to the next phase of their educational or career program? Are the types of research experiences and education clearly articulated for the appropriate career level of the participant? Are genomic science, genomic medicine or genomes and society topics prominently integrated into planned activities? How does the plan take advantage of the research infrastructure of the applicant institution and other similar programs supported by NHGRI and the PD's/PI's institution? What is the value added and does this program differ from ongoing activities?

              For renewal applications, how successful was the program in supporting participants to the next phase of their career in genomics research? Do they show evidence of participants applying to and being accepted in the next stage? Do they show evidence of participants having publications/abstracts resulting from their experience in the program?

              Will the scientific and educational environment of the proposed program contribute to its intended goals? Is there a plan to take advantage of this environment to enhance the educational value of the program? Is there tangible evidence of institutional commitment? Is there evidence that the faculty have sufficient institutional support to create a sound educational environment for the participants? Where appropriate, is there evidence of collaboration and buy-in among participating programs, departments, and institutions?

              Collectively, do the research groups provide access to a broad set of research experiences in genome sciences, genomic medicine and/or genomics and society so that the participants can use the skills, knowledge and expertise to function in any research program focused on genomics? Does the institution have sufficient and varied peer-reviewed projects in the areas of interest to sustain an infrastructure consistent with the intent and duration of this program? If applicable, are the plans to coordinate and collaborate with other NHGRI-supported R25 diversity and/or T32 programs adequate such that there will be synergy amongst the programs? Does the institution have the potential to sustain an intense research program in genome sciences, genomic medicine and/or genomics and society for at least ten years?

              As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

              Protections for Human Subjects

              For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: (1) risk to subjects, (2) adequacy of protection against risks, (3) potential benefits to the subjects and others, (4) importance of the knowledge to be gained, and (5) data and safety monitoring for clinical trials.

              For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: (1) the justification for the exemption, (2) human subjects involvement and characteristics, and (3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

              Inclusion of Women, Minorities, and Individuals Across the Lifespan

              When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

              The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed (3) interventions to minimize discomfort, distress, pain and injury and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

              Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

              For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

              For Renewals, the committee will consider the progress made in the last funding period, and the success of the program in attracting individuals from diverse populations, including populations underrepresented in biomedical, behavioral and clinical research on a national basis.

              For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

              As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

              Recruitment Plan to Enhance Diversity

              Peer reviewers will separately evaluate the recruitment plan to enhance diversity after the overall score has been determined. Reviewers will examine the strategies to be used in the recruitment of individuals from underrepresented groups. The review panel’s evaluation will be included in the summary statement. Plans will be rated as acceptable or unacceptable, and the summary statement will provide the consensus of the review committee.

              Training in the Responsible Conduct of Research

              Taking into account the specific characteristics of the proposed research education program, the level of participant experience, the reviewers will evaluate the adequacy of the proposed RCR training in relation to the following five required components: 1) Format - the required format of instruction, i.e., face-to-face lectures, coursework, and/or real-time discussion groups (a plan with only on-line instruction is not acceptable) 2) Subject Matter - the breadth of subject matter, e.g., conflict of interest, authorship, data management, human subjects and animal use, laboratory safety, research misconduct, research ethics 3) Faculty Participation - the role of the program faculty in the instruction 4) Duration of Instruction - the number of contact hours of instruction, taking into consideration the duration of the program and 5) Frequency of Instruction –instruction must occur during each career stage and at least once every four years. See also: NOT-OD-10-019. The review panel’s evaluation will be included in the summary statement. Plans will be rated as acceptable or unacceptable, and the summary statement will provide the consensus of the review committee.

              Applications from Foreign Organizations

              Generally not applicable. Reviewers should bring any concerns to the attention of the Scientific Review Officer.

              Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan 2) Sharing Model Organisms and 3) Genomic Data Sharing Plan. If support for development, maintenance, or enhancement of software is requested in the application, the reviewers will comment on the proposed software dissemination plan.

              Budget and Period of Support

              Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

              Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NHGRI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.


              As part of the scientific peer review, all applications:

              • May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
              • Will receive a written critique.

              Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications . Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council for Human Genome Research. The following will be considered in making funding decisions:

              • Scientific and technical merit of the proposed project as determined by scientific peer review.
              • Availability of funds.
              • Relevance of the proposed project to program priorities.

              After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

              Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

              If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

              A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

              Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

              Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

              Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols."

              Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

              For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

              In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

              When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually. Continuation support will not be provided until the required forms are submitted and accepted. Programs that involve participants should report on education in the responsible conduct of research and complete a Training Diversity Report, in accordance with the RPPR Instruction Guide.

              Additionally, applicants must submit the NRSA Training Table 8A: Predoctoral Program Outcome (for graduate students) and/or 8D: Undergraduate Program Outcomes (for postbaccalaureate and undergraduate students), as applicable, in Section G1 of the Research Performance Progress Report (RPPR). Sample and table description can be found at https://grants.nih.gov/grants/forms/data-tables.htm.

              The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

              Failure by the grantee institution to submit required forms in a timely, complete, and accurate manner may result in an expenditure disallowance or a delay in any continuation funding for the award.

              In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

              • The institution must submit a completed Statement of Appointment (PHS Form 2271) for each participant appointed full time for eight weeks or more or the equivalent. Grantees must submit the PHS 2271 data electronically using the xTrain system. More information on xTrain is available at xTrain (eRA Commons). An appointment or reappointment may begin any time during the budget period, but not before the budget period start date of the grant year.
              • Participant Termination Notice: Within 30 days of the end of the total support period for each participant, the institution must submit a Termination Notice (PHS Form 416-7) via xTrain for each participant appointed full time for eight weeks or more, or the equivalent.
              • If funds are provided for program evaluation, then any written evaluation report must be provided as an attachment to Section G.1 of the RPPR. Please name your file “evaluation report" as appropriate

              A final RPPR and the expenditure data portion of the Federal Financial Report are required for closeout of an award as described in the NIH Grants Policy Statement.

              In carrying out its stewardship of human resource-related programs, the NIH or its Institutes and Centers will periodically evaluate their R25 research education programs, employing the measures identified below. In assessing the effectiveness of its research education investments, NIH may request information from databases, PD/PIs, and from participants themselves. Where necessary, PD/PIs and participants may be contacted after the completion of a research education experience for periodic updates on participants’ subsequent educational or employment history and professional activities.

              Upon the completion of a program evaluation, NIH and its ICs will determine whether to (a) continue a program as currently configured, (b) continue a program with modifications, or (c) discontinue a program.

              In evaluating this research education program NHGRI expects to use the following evaluation measures for all career levels (except when noted in parenthesis):

              • Aggregate number and demographic characteristics of participants
              • Educational level of participants at the start of the program
              • Participants’ feedback on the program
              • New knowledge or skills acquired
              • Subsequent educational/career progress, including:

              o (For undergraduates) successful completion of an undergraduate degree in a field relevant to the NHGRI mission

              o (For undergraduates and postbaccalaureates) enrollment in an advanced degree program in a field relevant to the NHGRI mission

              o (For undergraduates and postbaccalaureates) successful completion of an advanced degree program in a field relevant to the NHGRI mission

              o Subsequent participation in a formal research training or career development program in a field relevant to the NHGRI mission

              o Subsequent employment in a research field relevant to the NHGRI mission

              o Subsequent authorship of scientific publications in a field relevant to the NHGRI mission

              o Subsequent independent research grant support from NIH or another source.

              We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

              eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

              Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
              Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

              General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
              Email: [email protected] (preferred method of contact)
              Telephone: 301-945-7573

              Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
              Contact Center Telephone: 800-518-4726
              Email: [email protected]

              Tina Gatlin, Ph.D.
              National Human Genome Research Institute (NHGRI)
              Telephone: 301-480-2280
              Email: [email protected]

              Lynn Mertens King, PhD
              Research Training and Career Development Branch
              National Institute of Dental and Craniofacial Research
              Telephone: 301-594-5006
              Email: [email protected]

              Lu Wang, PhD
              Translational Genomics Research Branch
              National Institute of Dental and Craniofacial Research
              Telephone: (301) 594-4846
              Email: [email protected]

              Rudy Pozzatti, Ph.D.
              National Human Genome Research Institute (NHGRI)
              Telephone: 301-402-8739
              Email: [email protected]

              Yasaman Shirazi, PhD
              National Institute of Dental and Craniofacial Research (NIDCR)
              Telephone: 301-594-5593
              Email: [email protected]

              Devon Bumbray-Quarles
              National Human Genome Research Institute (NHGRI)
              Telephone: 301-451-7928
              Email: [email protected]

              Dede Rutberg, MBA
              National Institute of Dental and Craniofacial Research (NIDCR)
              Telephone: 301-594-4798
              Email: [email protected]

              Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

              Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.


              Our COVID-19 Research

              Campus Surveillance Testing

              Optimizing COVID-19 control with asymptomatic surveillance testing in a university environment.
              Cara E. Brook, Graham R. Northrup, Alexander J. Ehrenberg, Jennifer Doudna, and Mike Boots.
              &mdash medRxiv preprint

              Launching a saliva-based SARS-CoV-2 surveillance testing program on a university campus.
              Alexander J. Ehrenberg, Erica A. Moehle, Cara E. Brook, Andrew H. Doudna Cate, Lea B. Witkowsky, Rohan Sachdeva, Ariana Hirsch, Kerrie Barry, Jennifer R. Hamilton, Enrique Lin-Shiao, Shana McDevitt, Luis Valentin-Alvarado, Kaitlyn N. Letourneau, Lauren Hunter, Kathleen Pestal, Phillip A. Frankino, Andrew Murley, Divya Nandakumar, Elizabeth C. Stahl, Connor Tsuchida, Holly K. Gildea, Andrew G. Murdock, Megan L. Hochstrasser, Lucie Bardet, Carolyn Sherry, IGI SARS-CoV-2 Consortium, Anna Harte, Guy Nicolette, Petros Giannikopoulos, Dirk Hockemeyer, Maya Petersen, Fyodor D. Urnov, Bradley R. Ringeisen, Mike Boots, Jennifer A. Doudna
              &mdash Publication: Launching a saliva-based SARS-CoV-2 surveillance testing program on a university campus

              Diagnostics

              Next-generation CRISPR-based diagnostics for SARS-CoV-2
              Jennifer Doudna, Patrick Hsu, and Dave Savage, UC Berkeley. Read more >

              Detection of active SARS-CoV-2 infections in crude and complex biofluids
              Markita Landry, UC Berkeley. Read more >

              • Research spotlight: Markita Landry on Rapid, Nanosensor-Based Tests
              • medRxiv preprint: Rapid SARS-CoV-2 Detection by Carbon Nanotube-Based Near-Infrared Nanosensors
              • medRxiv preprint: Extraction of Viral Nucleic Acids with Carbon Nanotubes Increases SARS-CoV-2 RT-qPCR Detection Sensitivity

              Robotic RNA extraction for SARS-CoV-2 surveillance using saliva samples
              Jennifer R. Hamilton, Elizabeth C. Stahl, Connor A. Tsuchida, Enrique Lin-Shiao, C. Kimberly Tsui, Kathleen Pestal, Holly K. Gildea, Lea B. Witkowsky, Erica A. Moehle, Shana L. McDevitt, Matthew McElroy, Amanda Keller, Iman Sylvain, Ariana Hirsh, Alison Ciling, Alexander J. Ehrenberg, IGI SARS-CoV-2 Consortium, Bradley R. Ringeisen, Garth Huberty, Fyodor D. Urnov, Petros Giannikopoulos, Jennifer A. Doudna.
              &mdash medRxiv preprint

              IGI-LuNER: single-well multiplexed RT-qPCR test for SARS-CoV-2
              Elizabeth C. Stahl, Connor A. Tsuchida, Jennifer R. Hamilton, Enrique Lin-Shiao, Shana L. McDevitt, Erica A. Moehle, Lea B. Witkowsky, C. Kimberly Tsui, Kathleen Pestal, Holly K. Gildea, Matthew McElroy, Amanda Keller, Iman Sylvain, Clara Williams, Ariana Hirsh, Alison Ciling, Alexander J. Ehrenberg, IGI SARS-CoV-2 Consortium, Fyodor D. Urnov, Bradley R. Ringeisen, Petros Giannikopoulos, Jennifer A. Doudna.
              &mdash medRxiv preprint

              Epidemiology, Surveillance, and Viral Sequencing

              Next-generation sequencing to inform COVID-19 outbreak response in Madagascar
              Cara E. Brook, UC Berkeley. Read more >

              Rapid, low-cost, high-throughput viral and metagenome sequencing of COVID-19 patient samples for outbreak surveillance
              Liana Lareau and Stacia Wyman, UC Berkeley. Read more >

              Real-time genomic tracking of SARS-CoV-2 evolution and spread in Northern California
              Charles Chiu, UCSF. Read more >
              &ndash Publication: Genomic surveillance reveals multiple introductions of SARS-CoV-2 into Northern California

              Community-based longitudinal study of asymptomatic carriage and seroprevalence of SARS-CoV-2 in the Northern California Bay Area
              Eva Harris and Lisa Barcellos, UC Berkeley. Read more >

              SARS-CoV-2 Virology, Life Cycle, and Pathogenesis

              Discovering and targeting the RNA structural code underlying SARS-CoV-2 life cycle
              Hani Goodarzi, UCSF. Read more >
              &ndash Research Spotlight: Hani Goodarzi on RNA Secondary Structure

              Exploring SARS-CoV-2 viruses using CRISPR-based yeast recombineering
              Raul Andino and Hiten Madhani, UCSF. Read more >
              &ndash Research Spotlight: Hiten Madhani on Developing a Live-Attenuated Vaccine

              Social Science

              Virtual mentoring: Impacts of COVID-19 on the next generation of the scientific workforce.
              Laleh Coté, LBNL & UC Berkeley Anne Baranger, UC Berkeley and Colette Flood, LBNL.
              Read more >
              &ndash Research Spotlight: Laleh Coté on Virtual Mentoring

              Structural Biology and Therapeutic Targets

              Structural studies of the COVID-19 replication/transcription holo-complex
              Eva Nogales, UC Berkeley. Read more >

              The QCRG structural consortium: targeting the host-pathogen interface
              Oren Rosenberg and Kliment Verba, UCSF. Read more >
              &mdash bioRxiv Preprints: Multiple papers

              Determining factors that inhibit the interaction between COVID-19 and its receptor on lung epithelial cells
              Robert Stroud, UCSF. Read more >
              &ndash bioRxiv Preprint: Bi-paratopic and multivalent human VH domains neutralize SARS-CoV-2 by targeting distinct epitopes within the ACE2 binding interface of Spike
              &ndash bioRxiv Preprint: Peptide antidotes to SARS-CoV-2 (COVID-19)

              Vaccines and Therapeutics

              Epigenome editing: a new prophylactic SARS-CoV-2 therapeutic
              Luke Gilbert, UCSF and Jonathan Weissman, Whitehead Institute. Read more >
              &ndash Research Spotlight: Luke Gilbert on an Epigenetic Pretreatment

              A Cas9-based shuttle enhancing cellular import and nuclear localization of plasmid DNA as an adjuvant of non-viral SARS-CoV-2 DNA vaccines entering human trials
              Alex Marson, UCSF and Ross Wilson, UC Berkeley. Read more >

              Screening for small molecule inhibitors of SARS-CoV-2 enzymes
              Dan Nomura, Jamie Cate, et al., UC Berkeley. Read more >
              &ndash bioRxiv Preprint: Screening a library of FDA-approved and bioactive compounds for antiviral activity against SARS-CoV-2



Comments:

  1. Wethrby

    hee hee

  2. Lisle

    You have to be an optimist.

  3. Wagner

    You read this and think….



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