PAR-27-071: Discovery of the Genetic Basis of Childhood Cancers and of Congenital Anomalies: Gabriella Miller Kids First Pediatric Research Program (X01 Clinical Trial Not Allowed)

PAR-27-071: 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 NIH Common Fund. Supports research to discover the genetic basis of childhood cancers and congenital anomalies through the Gabriella Miller Kids First Pediatric Research Program.

PAR-27-071: Discovery of the Genetic Basis of Childhood Cancers and of Congenital Anomalies: Gabriella Miller Kids First Pediatric Research Program (X01 Clinical Trial Not Allowed) 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 Notice of Funding Opportunity (NOFO) 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 NOFO will be administered by a cross-NIH team led by the National Cancer Institute ( NCI ) and 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 Congenital Anomalies: Gabriella Miller Kids First Pediatric Research Program (X01 Clinical Trial Not Allowed) X01 Resource Access Award Check for any recent Notices of NIH Policy Changes that may impact application requirements. Funding Opportunity Number (FON) Companion Funding Opportunity See Part 2, 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 genomic data generating centers.

Applicants are encouraged to propose sequencing of existing pediatric cancer or congenital anomaly cohorts to elucidate the genetic contribution (somatic and/or germline) to childhood cancers, to investigate the genetic etiology of congenital anomalies, to study the molecular basis of the associations between congenital anomalies 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 clinical-grade sequencing, long-read sequencing, proteomics, and epigenomic assays of tumor or affected tissue, when justified. Applicants are encouraged to propose cohorts to increase 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. Funding Opportunity Goal(s) This listing covers the Common Fund, administered by the Office of Strategic Coordination (OSC) in the NIH Office of the Director which offers assistance awards or supplements to assistance awards.

Open Date (Earliest Submission Date) Applications are due January 11th, 2027 (01/11/2027). 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.

AIDS Application Due Date(s) A Scientific Merit Review will be performed by members of the Gabriella Miller Kids First Working Group in March 2027. Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ).

Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - Application Guide , follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review. 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. Use the NIH ASSIST system to prepare, submit and track your application online. 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. Use Grants.

gov Workspace to prepare and submit your application and eRA Commons to track your application. Part 1. Overview Information Part 2.

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

Eligibility Information Section IV. Application and Submission 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. Notice of Funding Opportunity Description The Gabriella Miller Kids First Pediatric Research Program (Kids First) was established by The Gabriella Miller Kids First Research Act, or Kids First ( https://www. congress.

gov/bill/113th-congress/house-bill/2019/text ), for an initial 10 years, 2015-2024. The program was reauthorized as Kids First 2. 0 by the 118th Congress for an additional five years, and the program was transferred from The Common Fund to the Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI).

DPCPSI and Common Fund have agreed that Common Fund would continue to administer Kids First on behalf of DPCPSI. The overall goal of the Gabriella Miller Kids First Program is to help researchers uncover new insights into the biology of childhood cancer and congenital anomalies, including the discovery of shared genetic pathways between these disorders, to understand the underlying mechanisms of disease.

This understanding would lead to novel and more refined prevention tools, diagnostics, and ultimately more targeted therapies and interventions for patients and families.

This funding opportunity builds upon prior NOFOs ( PAR-15-259 , PAR-16-150 , PAR-17-063 , PAR-18-583 , PAR-19-104 , PAR-19-390 , PAR-21-040 , PAR-22-054 , PAR-23-035 , and PAR-24-082 ) and is intended to identify samples for germline whole genome sequencing (standard short-read whole genome sequencing or long-read sequencing, or clinical-grade 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 congenital anomalies.

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 (whether short-, long-, or clinical-grade sequencing) and other omic assays, as soon as possible after the application due date of this NOFO.

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 NOFO offers a protocol of sequencing the whole genome from high quality genomic DNA by one of Kids First Program's genomic data generating 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 s from previous short-read sequencing and analysis. Clinical-grade sequencing may be proposed but must be justified. Proteomics may be proposed, with justification, and may be accommodated if available.

Project design will be finalized in discussions among the X01 investigators, the genomic data generating centers, Kids First Data Resource Center, and NIH program staff.

For childhood cancer cohorts: This NOFO invites applications that propose sequencing of DNA samples from childhood cancer cohorts (as well as 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 genetic basis, predispositions, or genomic aberrations 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). Clinical-grade sequencing may be proposed but must be justified.

Proteomics and/or metabolomics of tumor samples may be proposed, with justification; and may be accommodated if available. Studies where the probands were born with congenital anomalies 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 s from tumor samples is encouraged when sequencing and analysis of the tumor will provide additional insight into the cancer(s) under study.

For congenital anomalies cohorts: This NOFO also invites applications that will propose sequencing of DNA samples from subjects with those categories of congenital anomalies 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 congenital anomalies that might be answered by whole genome sequencing, as well as genome, exome, transcriptome, and epigenomic sequencing of affected tissue. Clinical-grade sequencing may be proposed but must be justified. Proteomics of relevant tissue samples may be proposed, with justification; and may be accommodated if available.

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 congenital anomalies 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 congenital anomalies.

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 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 un - sequenced 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 under study.

Specific Requirements and Expectations for this Opportunity The cohorts selected under this NOFO 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 (DULs) for proposed samples should be indicated on the submitted Institutional Certification using the current NIH template. Cohort samples that have consents allowing 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. Examples of other data types include other omics data, imaging data, and information from health records. Projects selected under this NOFO will be expected to work in a collaborative manner with a designated Kids First Program genomic data generating center.

These 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 data generating center for custom analysis and validation of variants for a subset of cases.

Such scientific collaboration will be arranged between the applicant and data generating 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 NOFO 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 congenital anomalies 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. 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 congenital anomalies 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 has developed a data resource in the cloud to accelerate pediatric cancer and congenital anomalies 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 study 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 contribution of genetic factors to human health due to the relative frequencies of both deleterious and beneficial alleles among human populations is an important area of interest. 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, congenital anomalies 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 congenital anomalies.

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 congenital anomalies 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 financial assistance 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 How to Apply - Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO. Not Allowed: Only accepting applications that do not propose clinical trials.

Note: Applications may propose activities involving human subjects that are not deemed 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.

Not applicable; there are no funds associated with a resource access award. 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 data generating 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 NOFO.

Section III.

Eligibility Information Higher Education Institutions - Includes all types Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education 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 Foreign Organizations/Foreign Collaborations Non-domestic (non-U.S.) Entities (Foreign Organizations) 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 must complete and maintain the following registrations as described in the How to Apply - 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications for additional information 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. Foreign organizations must obtain a NATO Commercial and Government Entity (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 registrations; 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. All PD(s)/PI(s) must be registered with ORCID . The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID.

For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help .

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 their organization to develop an application for 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 How to Apply - Application Guide . This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1. 2 Definition of Terms.

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 NIH Grants Policy Statement Section 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 NIH Grants Policy Statement 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 NOFO. 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 How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise (in this NOFO, in a policy notice , or other notice from NIH Guide for Grants and Contracts ).

Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed , with the following exceptions or additional requirements: For this specific NOFO, the Research Strategy section is limited to 6 pages .

Instructions for Application Submission The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO. All instructions in the How to Apply - 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 How to Apply - Application Guide must be followed.

SF424(R&R) Other Project Information All instructions in the How to Apply - 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://grants.

nih. gov/policy-and-compliance/policy-topics/sharing-policies/gds/completing-institutional-certification-form ), 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 genomic data generating 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 contaminated with bacteria could reduce the total number of samples that can be sequenced; therefore, blood- or tissue-derived nucleic acids are preferable. DNA or other material from patient-derived cell lines will not be accepted due to the possible introduction of mutations that could confound the identification of disease-causing rare variants.

Additionally, DNA or RNA from samples that have undergone decalcification will not be accepted. Describe the status of the DNA, RNA, and other samples and their storage/preservation formats that will be provided, including the extraction methods used for each source and the approximate nucleic acid concentrations. Address their quantity and quality in terms of suitability for whole genome sequencing and/or other technology proposed.

Describe the quality metric and method of quantification used. Describe sample availability for shipment to the genomic data generating center(s) per cohort or sub-cohort proposed. For applications proposing chromatin accessibility assays, such as ATAC-seq, describe the tissue source and material that will be provided.

For tumor specimens, describe the pathology review to which the specimens were subjected and the percentage of tumor cells within the specimen used for DNA and/or RNA isolation.

3) Clinical, Phenotypic, and Demographic Data: Describe what clinical, phenotypic, and demographic information was collected from all study participants and what is available for submission to the Kids First Data Resource to be shared with the wider research community.

At a minimum, the following data elements are expected: age at enrollment and/or age at diagnosis, diagnoses (e.g., type of birth defect, primary tumor type), phenotypes for affected cases (list all variables collected), phenotypes for unaffected family members (list all variables collected), age at last known vital status, clinical information (list all available clinical data elements), and family medical history (e.g., family history of cancer or congenital anomalies).

Describe whether other data types are available. Describe whether electronic health records may be available for additional data extraction. For an example template of clinical and phenotypic data elements, visit https://commonfund.

nih. gov/kidsfirst/FAQ . If appropriate, describe any available environmental or exposure data.

If a proposed cohort is selected, a data dictionary or additional data elements may be requested. 4) Family Structure (if applicable): If proposing a non-trio design, provide any additional information that will help explain the family structures for your proposed cohort (e.g., pedigrees). Convey the total number of affected and unaffected family members proposed for sequencing.

For optional