Discovery of the Genetic Basis of Childhood Cancers and of Congenital Anomalies: Gabriella Miller Kids First Pediatric Research Program (X01 Clinical Trial Not Allowed)

Discovery of the Genetic Basis of Childhood Cancers and of Congenital Anomalies: Gabriella Miller Kids First Pediatric Research Program (X01 Clinical Trial Not Allowed) is sponsored by National Institutes of Health (NIH). Program supporting research to identify genetic causes of childhood cancers and congenital anomalies, aiming to enhance understanding and treatment.

Expired PAR-23-035: Discovery of the Genetic Basis of Childhood Cancers and of Structural Birth Defects: Gabriella Miller Kids First Pediatric Research Program (X01 Clinical Trial Not Allowed) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations Office of Strategic Coordination ( Common Fund ) This FOA is a Common Fund initiative ( Common Fund ) through the NIH Office of the Director, Office of Strategic Coordination ( https://dpcpsi. nih. gov/ ).

All NIH Institutes and Centers participate in Common Fund initiatives. The FOA will be administered by a trans-NIH team led by the Eunice Kennedy Shriver National Institute of Child Health and Human Development ( NICHD ).

Funding Opportunity Title Discovery of the Genetic Basis of Childhood Cancers and of Structural Birth Defects: Gabriella Miller Kids First Pediatric Research Program (X01 Clinical Trial Not Allowed) X01 Resource Access Award Notices of Special Interest associated with this funding opportunity December 11, 2023 - This PAR has been reissued as PAR-24-082 NOT-RM-23-007 - Notice of Pre-Application Webinar for PAR-23-035: Discovery of the Genetic Basis of Childhood Cancers and of Structural Birth Defects: Gabriella Miller Kids First Pediatric Research Program (X01 Clinical Trial Not Allowed) NOT-OD-22-195 New NIH "FORMS-H" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2023 NOT-OD-22-189 Implementation Details for the NIH Data Management and Sharing Policy NOT-OD-22-198 Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023 NOT-OD-23-012 Reminder: FORMS-H Grant Application Forms & Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity See Section III.

3. Additional Information on Eligibility . Assistance Listing Number(s) Funding Opportunity Purpose As part of the Gabriella Miller Kids First Pediatric Research Program ( Kids First Program ), the NIH invites applications to submit samples from pediatric cohorts for whole genome sequencing at a Kids First Program-supported sequencing center.

Applicants are encouraged to propose sequencing of existing pediatric cancer or structural birth defect cohorts to elucidate the genetic contribution (somatic and/or germline) to childhood cancers, to investigate the genetic etiology of structural birth defects, to study the molecular basis of the associations between birth defects and increased cancer risk, or to expand the range of pediatric disorders included within the Kids First Data Resource .

The program will accept applications that propose whole genome, exome, and transcriptome sequencing, as well as epigenomic assays of tumor or affected tissue, when justified. Applicants are encouraged to propose cohorts of underrepresented racial and ethnic groups or to increase racial and ethnic representation of existing Kids First Program projects .

These data, and associated clinical and phenotypic data, will become part of the Kids First Data Resource Center for sharing with the research community. Open Date (Earliest Submission Date) Letter of Intent Due Date(s) Renewal / Resubmission / Revision (as allowed) All applications are due by 5:00 PM local time of applicant organization.

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. Required Application Instructions It is critical that applicants follow the instructions in 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 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 may be delayed or not accepted for review. Part 1. Overview Information Part 2.

Full Text of Announcement Section I. Funding Opportunity Description Section II. Award Information Section III.

Eligibility Information Section V. Application Review Information Section VI. Award Administration Information Section VII.

Agency Contacts Section VIII. Other Information Part 2. Full Text of Announcement Section I.

Funding Opportunity Description In response to The Gabriella Miller Kids First Research Act ( https://www. congress. gov/bill/113th-congress/house-bill/2019/text ), NIH, through the Common Fund, established the Gabriella Miller Kids First Pediatric Research Program (Kids First program) in 2015.

The Kids First program is a ten-year effort (2015 - 2024) to enable researchers, clinicians, and patients to work together to accelerate collaborative research and promote new discoveries for children affected with cancer and structural birth defects.

The goal of the program is to help researchers uncover new insights into the biology of childhood cancer and structural birth defects, including the discovery of shared genetic pathways between these disorders.

The Kids First Data Resource Center hosts genomic and phenotypic data of high value to the pediatric research community, facilitates data sharing and data analysis in the cloud across diverse conditions, and promotes interoperability to accelerate collaborative research and promote new discoveries.

During the first seven years of this program, data from approximately 30,000 participants were generated and made available following sequencing of DNA, and some RNA, samples from pediatric cancer and structural birth defects projects.

In addition to increased understanding of individual pediatric conditions, a goal of the Kids First Data Resource is to enable discovery of shared pathways whose disruption may lead to structural birth defects and/or susceptibility to childhood cancer. Therefore, representation of a wide variety of pediatric cancers and structural birth defects within the Kids First Data Resource Center is essential.

In addition, the Kids First Program seeks to increase diversity within our datasets and to improve coverage of underrepresented populations (e.g. Blacks or African Americans, Hispanics or Latinos, American Indians or Alaska Natives, Native Hawaiians and other Pacific Islanders).

The overall goal of the program is to help researchers understand the underlying mechanisms of disease, leading to novel and more refined prevention tools, diagnostics, and ultimately more targeted therapies and interventions.

This funding opportunity builds upon prior FOAs ( PAR-15-259 , PAR-16-150 , PAR-17-063 , PAR-18-583 , PAR-19-104 , PAR-19-390 , PAR-21-040 , and PAR-22-054 ) and is intended to identify samples for germline whole genome sequencing (standard short-read whole genome sequencing or long-read sequencing, when justified), as well as genomic, exome, transcriptomic (RNA), and epigenomic (e.g., genome-wide methylation, chromatin accessibility) data generation for tumors and/or affected tissue that will help elucidate genetic contributions to childhood cancers and the etiology of structural birth defects.

Data obtained from these projects will be analyzed and processed, to generate derived files and summary data, which will be compiled and made accessible alongside raw data and metadata, through the Kids First Data Resource Center’s portal .

Types of Research Projects The Kids First Program seeks applications for sample sets that can be ready for whole genome sequencing, as soon as possible after the application due date of this FOA. In general, applications may aim to discover influential genetic variants underlying their targeted disorder using various study designs (e.g., trio-based, family-based, or other).

An integrative -omics approach (e.g. transcriptomic) may also be taken. This FOA offers a protocol of sequencing the whole genome from high quality genomic DNA by one of Kids First Program’s sequencing centers, as well as protocols for exome, transcriptomic, and epigenomic sequencing and analyses of tumor/affected tissue specimens (if available and justified).

As sequencing technologies are constantly evolving, additional or alternative approaches may be proposed. For example, applicants may propose long-read sequencing approaches based on evidence of structural variation from previous short-read sequencing and analysis. Project design will be finalized in discussions among the X01 investigators, the sequencing centers, Kids First Data Resource Center, and NIH program staff.

For childhood cancer cohorts: This FOA invites applications that propose sequencing of DNA samples from childhood cancer cohorts (as well as DNA and RNA samples from tumors) for which a genetic basis (germline or somatic) is suspected but not identified, or for which understanding of recurring somatic mutations may address important questions of biology and therapy, or that analysis may uncover relationships with conditions already represented in the Kids First Data Resource.

Proposed study populations should address important questions about the genetics/genomics of childhood cancers that might be answered by the approach proposed (e.g. whole genome sequencing of germline DNA, as well as tumor genome, exome, transcriptome, and epigenomic sequencing when tumor tissue is available).

Studies where the probands were born with structural birth defects and subsequently diagnosed with childhood cancer are also encouraged. All study designs, with appropriate scientific justification, will be considered.

Investigators may consider a trio or quad study design with the study population consisting of germline and tumor samples collected from participants with childhood cancer and their parents or affected first degree relatives, including those where the proband has previously been sequenced.

Note that submission of material from tumor samples is encouraged when sequencing and analysis of the tumor will provide additional insight into the cancer(s) under study.

For structural birth defects cohorts: This FOA also invites applications that will propose sequencing of DNA samples from subjects with those categories of structural birth defects that are appropriate for whole genome sequencing; that are not yet well represented in the Kids First dataset, or that analysis may uncover relationships with conditions already represented in the Kids First dataset.

Proposed study populations should address important questions about the genetics/genomics of structural birth defects that might be answered by whole genome sequencing, as well as genome, exome, transcriptome, and epigenomic sequencing of affected tissue. All study designs, with appropriate scientific justification, will be considered.

One example is that of a trio study design with the study population consisting of samples collected from participants with structural birth defects and their parents, including those where the proband has previously been sequenced. Strong justification for the proposed sample size is expected in each application.

Study populations with defects that affect multiple organ systems, or that are associated with susceptibility to childhood cancers, are especially encouraged. Populations with syndromic conditions that exhibit intellectual or neurobehavioral disabilities as part of the phenotype are acceptable, as long as the focus of the project is on associated structural birth defects.

Note that submission of material from affected tissue samples is encouraged when sequencing and analysis of the tissue will provide additional insight into the structural birth defect(s) under study.

For all cohorts: Investigators with small cohort sizes are encouraged to collaborate with other investigators and pool samples together to establish adequate power to uncover variants with relevant implications to the cancer(s) or birth defects(s) under study, or to improve representation of racial and ethnic diversity in the datasets.

This approach is especially relevant for disease conditions that have not yet been sequenced by the Kids First Program.

Investigators who have previously sequenced genomic DNA from probands and who have unsequenced nucleic acid samples from their parents, siblings, tumor, and/or affected tissue are also encouraged to apply to have those samples sequenced, if it will result in additional insights into the genetic contribution to the cancer(s) or birth defects(s) under study.

Specific Requirements and Expectations for this Opportunity The cohorts selected under this FOA must have already extracted genomic DNA or samples that are ready to be extracted (DNA and RNA from tumors/affected tissue are desirable but optional.) Participants must have given consent to allow broad sharing and use of individual-level sequence and associated clinical and phenotypic data through dbGaP or other NIH-approved repositories.

Unless otherwise prohibited, clinical and phenotypic data will be openly shared through the Kids First Data Resource Center’s portal . Consent groups and/or data use limitations for proposed samples should be indicated on the submitted Institutional Certification using the current NIH template.

Cohort samples that have consents that allow for broad data sharing and use, to include combining and comparing datasets across disease areas, (i.e. for General Research Use ) are of higher priority. Conditions not previously incorporated into the Kids First dataset are desirable. A list of prior Kids First Program X01 projects is available for reference.

No funds will be provided through this opportunity for collecting samples, performing additional phenotyping, acquiring other data types, obtaining new consent for existing samples, or performing data analysis. However, other NIH initiatives may provide support for these activities. Cohorts that have provided consent to be re-contacted for additional studies are therefore encouraged.

Cohorts proposed for sequencing must include a minimum amount of associated clinical and phenotypic data sufficient to enable association analysis with genomic variants. Applications with rich clinical and phenotypic data that can be shared to facilitate cross-disease research among the pediatric research community will be prioritized.

Cohorts of underrepresented racial and ethnic groups or that add diversity to existing Kids First Program datasets are encouraged. Projects selected under this FOA will be expected to work in a collaborative manner with a designated Kids First Program sequencing center.

The sequencing centers will produce sequence read and called variant data sets, as well as genome-wide methylation profiling and chromatin accessibility assay data (e.g., ATAC sequencing), where applicable. Some applicants may wish to further collaborate with the sequencing center for custom analysis and validation of variants for a subset of cases.

Such scientific collaboration will be arranged between the applicant and sequencing center staff with oversight from the NIH, however such services may reduce the total number of samples that can be sequenced. Data from the studies selected under this FOA will be submitted to the Kids First Data Resource Center.

All Kids First data will be processed, harmonized, and made accessible through the cloud-based infrastructure of the Kids First Data Resource Center, where investigators are encouraged to interact with the data. PDs/PIs of selected cohort projects will participate in a collaborative effort to inform the development of the integrated data resource to maximize its impact on the research community.

Investigators selected for this opportunity will be notified by NIH Kids First program staff with the estimated number of samples approved for sequencing. Approval to access the sequencing capacity is conditional on the submission of a completed Institutional Certification covering all samples to be submitted for sequencing.

If the document does not meet the Kids First program's expectation for broad data sharing (i.e., General Research Use ), another cohort with broader sharing may be selected instead. After approval, investigators will work with the NIH and the designated sequencing center to determine the final number of samples to be sequenced, as well as which sequencing technologies will be used.

Details of sample and shipping requirements (amount, concentration, quality) will be provided to investigators. The intersection between human development and cancer is not a new concept. Multiple findings have substantiated the shared biology between birth defects and childhood cancer.

For example, BRAF , MAPK , and ALK mutations are found in both birth defects and cancers. These proteins are validated clinical oncology drug targets; thus suggesting potential new treatments for pediatric conditions. Most recently, a 2019 publication showed increased cancer risks for kids born with birth defects in a large-scale study including 10 million live births.

Genetic alterations underlie etiologic contributors to pediatric disease, including childhood cancers as well as multiple birth defects and related syndromes. Investigations of the genetic architecture of various diseases, by exome sequencing and other genome-wide interrogations, suggest that large sample sizes will be required to achieve a comprehensive understanding of the genetic etiology of these disorders.

Those studies highlight the genetic heterogeneity of various developmental disorders and the genetic overlap between various diseases. The Kids First Program is growing a data resource in the cloud to accelerate pediatric cancer and structural birth defects research leading to better prevention, diagnosis, and treatments for patients and families.

The program’s goal is to grow a resource with Findable, Accessible, Interoperable, and Reusable (FAIR) data, promote data sharing, develop tools for data analysis and data visualization, and foster collaborative research.

The Kids First Data Resource Center provides integrated data sets to increase power; catalogs myriad data sets to enable rational organization of data resources; and, facilitates cross-linking of diverse data sets to enable novel research collaborations and knowledge connections.

The Kids First Program is committed to increasing the balance of racial and ethnic groups previously left out of research studies and clinical trials with the goal to create more diverse cohorts resulting in more information about their health.

The increased risk of occurrence and mortality due to childhood cancer and birth defects depending on race and ethnic groups can be partially explained by socio-economic factors such as access to health care, mother’s lifestyle, environmental factors. These factors warrant further investigation, although are not specifically part of this program.

Approximately 3% of all babies born in the United States has a birth defect, and these are the leading cause of death for infants during the first year of life, summing to 20% of all infant deaths. Next to accidents, birth defects are the leading cause of death in children during the first four years of life and account for half of all pediatric hospitalizations.

Technical advances (such as the decreased cost of genomic sequencing) have made powerful tools available to help researchers uncover the genetic variants, genes, and pathways that underlie birth defects.

Together with our ability to describe clinical characteristics in detail, there are emerging opportunities for research on genetic and environmental influences on development and for illuminating common pathways that may link different birth defects. Cancer is the leading cause of death from disease among children.

Kids First Program’s workshops and symposia have emphasized the importance of further large-scale germline sequencing of well-annotated pediatric cancer patient and parent trios, as well as paired diagnostic and/or relapse tumor specimens when available and have emphasized the value of collecting and sharing rich clinical and phenotypic data. The causes of some pediatric cancers are not well understood.

Many of the rare familial cancer syndromes include pediatric cancers in which tumor formation is directly related to a structural defect or mutation in the germline. Historically, germline alterations were identified in only a small fraction of children with cancer, even in those with a family history of cancer in 1st or 2nd degree relatives.

However, with the advent of genome-wide sequencing, potentially causative germline alterations have been observed in approximately 10 percent of children with cancer. Germline sequencing data from many more children with cancer and birth defects are needed to fully elucidate the etiology of these conditions and accelerate the development of novel prevention, diagnostics, and treatments for patients.

The Gabriella Miller Kids First Pediatric Research Program (Kids First) staff intends to hold a Pre-Application Webinar for all interested prospective applicants. Webinar date and other details will be posted on the Kids First website: https://commonfund. nih.

gov/kidsfirst . See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information Other: A mechanism that is not a grant or cooperative agreement. Examples include access to research resources or pre-applications.

Application Types Allowed 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 trials.

Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards Not applicable; there are no funds associated with a resource access award. Application budgets are not limited but need to reflect the actual needs of the proposed project.

The scope of the proposed project should determine the project period. The maximum project period is 1 year. Investigators are expected to ship samples to designated Kids First Program’s sequence center within 6 months of the award notification.

This period may be extended only in exceptional cases upon justification and approval. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA. Section III.

Eligibility Information 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) For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized) Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Institutions) Applications Involving the NIH Intramural Research Program NIH intramural scientists may participate in this program as PD/PIs in accord with the Terms and Conditions provided in this FOA.

The requests by NIH intramural scientists will be limited to the incremental costs required for participation.

As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs).

These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the Common Fund through the NIH Intramural Program. NIH intramural scientists will participate in this program as PDs/PIs in accord with the Terms and Conditions provided in this FOA.

Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights. Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply. Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement , are allowed. 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. System for Award Management (SAM) 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.

Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM. gov registration process. The same UEI must be used for all registrations, as well as on the grant application.

eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants. gov registration; 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.

Grants. gov Applicants must have an active 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. Eligible Individuals (Program Director/Principal Investigator) 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. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019 .

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. This FOA does not require cost sharing as defined in the NIH Grants Policy Statement. 3.

Additional Information on Eligibility 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, per 2. 3.

7. 4 Submission of Resubmission Application . 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 2. 3.

9. 4 Similar, Essentially Identical, or Identical Applications ) Section IV. Application and Submission Information 1.

Requesting an Application Package 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. 2.

Content and Form of Application Submission It is critical that applicants follow the instructions in 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 may be delayed or not accepted for review. 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: Member of Working Group Leadership Gabriella Miller Kids First Pediatric Research Program All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

For this specific FOA, the Research Strategy section is limited to 6 pages. 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.

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages. All instructions in the SF424 (R&R) Application Guide must be followed. Total Federal Funds Requested: Enter $0.

Total Federal & Non-Federal Funds: $0. Estimated Program Income: Enter 0. SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide must be followed. Other Attachments : The application must include the following attachments. 1) Institutional Certification for Genomic Data Sharing: Provide the Institutional Certification(s) using the current NIH template ( https://osp.

od. nih. gov/scientific-sharing/institutional-certifications/ ), which demonstrates that it is permissible to share individual-level genomic data to be generated for all samples proposed, consistent with achieving the goals of the program.

Institutional Certifications specify the data use limitations and data use limitation modifiers, as determined by the institution's IRB (or equivalent body) after reviewing the informed consent agreed to by the participants. If the Institutional Certification is not available, provide a Provisional Certification and describe the anticipated data use limitations and associated modifiers separately.

If submitting a Provisional Certification with the application, please note that a completed Institutional Certification will be required before a final selection can be made. For guidance on obtaining an Institutional Certification, see: https://commonfund. nih.

gov/kidsfirst/FAQ . Describe the characteristics and number of specimens proposed for sequencing in computer readable table format. Describe the number of specimens currently ready to ship to a sequencing center, and those that could be shipped at a later date in the same fiscal year (please provide a timeline if all proposed samples are not currently ready for shipment).

Provide a detailed inventory of the sources of the DNA (and RNA or other material if available for tumors and/or affected somatic tissue): number of samples from blood, number of samples from saliva or buccal swabs, and number of samples from frozen tissue versus embedded tissue (including fixation method). Please note that costs associated with assaying/processing saliva samples