Gabriella Miller Kids First Pediatric Research Program

Frequently Asked Questions (FAQs)

1. What is the Kids First program?
   
   Childhood cancers and structural birth defects have profound, lifelong effects on patients and their families. While researchers are increasingly identifying the underlying biological causes of these conditions, the role of genetics is not yet fully understood. A better understanding will spur development of prevention, early detection, and therapeutic interventions. The Common Fund’s Gabriella Miller Kids First Pediatric Research Program (Kids First) will capitalize on exciting advances in genetics research by developing a large-scale data resource. The resource will allow researchers everywhere access to vast amounts of childhood cancer and structural birth defects genetics data that will greatly accelerate their research. In addition, there is considerable scientific evidence that examining childhood cancer and structural birth defects together will uncover new connections between them that would not have been uncovered had one or the other been examined independently. By integrating large amounts of genetic data from patients with childhood cancer and structural birth defects, Kids First will facilitate new discoveries and novel ways of thinking about these conditions. This is anticipated to accelerate scientific progress in pediatric research that will improve the lives of the children and families impacted by these conditions.
   
   For additional general information on the Kids First program and its history please visit the program overview page.


2. What are the major initiatives of the Kids First program?
    
   • Identify cohorts of children with childhood cancer and structural birth defects for whole genome (DNA) sequencing.
   • Develop the Gabriella Miller Kids First Pediatric Data Resource (Kids First Data Resource) that combines genomic sequence and clinical data, and make these data widely available to the entire research community.
   • Support analyses of the data accessible through the Kids First Data Resource to uncover new insights into the biology of childhood cancer and structural birth defects, including the discovery of shared genetic pathways between childhood cancer and structural birth defects. Kids First also will support development of new computational tools for analyzing large and complex genetics data sets.


3. Why study childhood cancer and structural birth defects together?
   
   Epidemiological studies show that children with birth defects are at a higher risk of also developing childhood cancer, suggesting that these different conditions may have the same underlying cause, such as the same DNA change or DNA changes in genes that work together in the same biological pathway. However, not much is known about these suspected pathways, in part because there have been few large-scale genetics studies that focused on both childhood cancer and structural birth defects. Thus, it is important to study children with these conditions together because these shared biological pathways may not be uncovered if researchers continue to study childhood cancer patients or structural birth defects patients independently of each other.
   
   The Kids First program provides a unique opportunity for researchers to analyze childhood cancer and structural birth defects genetics data together to uncover new DNA changes potentially contributing to these conditions. Understanding how these DNA changes affect a patient’s cells and tissues will accelerate the development of treatments and therapeutic interventions. The nature of scientific research and discovery makes it difficult to predict when such therapies may become widely available, but the Kids First program will build a strong foundation to enable development of therapies that might not otherwise be possible.


4. How does sequencing DNA of cohorts of children with childhood cancer and structural birth defects lead to new therapies?
   
   Humans share 99.9% of their DNA sequence with all other humans. The remaining 0.1% that is different between each of us is what determines our unique characteristics; like height, hair color or blood pressure. This is called genetic variation. The majority of genetic variation is harmless, but occasionally a change in DNA will occur that predisposes the carrier of the DNA change to a disorder like childhood cancer or a structural birth defect. Researchers want to understand how these changes contribute to disease because understanding could lead to the discovery of novel treatments.
   
   In order for researchers to find DNA changes that may be contributing to cancer or structural birth defects, they first compare the DNA sequences of children with cancer or structural birth defects to the parents without cancer or structural birth defects. If there are DNA changes that are shared between affected children (those with childhood cancer or structural birth defects) that are NOT shared between unaffected parents, then those changes could be responsible for the childhood cancer or structural birth defect. However, since most genetic variation is harmless, large numbers of parents and children must be sequenced in order to determine exactly which variants contribute to the condition and which variants are simply normal differences between people. Understanding which DNA changes lead to disease will help researchers develop prevention, early detection, and therapeutic interventions. The nature of scientific research and discovery makes it difficult to predict when such therapies may become widely available, but the Kids First program will build a strong foundation to enable development of therapies that might not otherwise be possible.


5. What is a data resource and why is Kids First developing one?
   
   A data resource contains large amounts of data and computational tools that can be used by many researchers, thereby accelerating research progress. In the case of the Kids First program, the data will be DNA sequences from dozens of cohorts of children with cancer or structural birth defects and their parents, comprising thousands of individuals. Because DNA sequence data (genetic data) is very large and complex, it requires sophisticated computing and analysis software. For example, in 2015, Kids First provided funds to sequence the DNA of approximately 6,000 patients and their families, generating approximately 18 trillion base pairs of information. (Information in DNA is stored as a code made up of base pairs and the order, or sequence, of these base pairs determines the information available for building and maintaining an organism). As the program sequences additional cohorts and incorporates genetic information from other existing data sets, the data resource will grow much larger. Special computer software designed specifically for handling and analyzing large and complex genetic data will be needed to look within these trillions and trillions of base pairs and find the small number of DNA changes that potentially contribute to childhood cancer and structural birth defects. Kids First will support the development of such software, and make it accessible to researchers through the Kids First Pediatric Data Resource.


6. How will the Kids First Data Resource help advance cancer and structural birth defects research?
   
   The Kids First Data Resource will provide many benefits to researchers.
   • The Kids First Data Resource will serve as a centralized database to assemble dispersed data sources together into one location. Independent of the Kids First program, there are already childhood cancer and structural birth defects genetics data available. However, the data are currently scattered in many different locations, hindering the ability of researchers to use the full breadth of data to make new discoveries. The Kids First Data Resource will aggregate Kids First-generated data together with additional data sets from outside this program. This will provide a single, convenient location for researchers to access unprecedented amounts of data, and will increase their ability to detect rare genetic changes that contribute to childhood cancer or structural birth defects.
   • The Kids First Data Resource will provide researchers with the necessary computational infrastructure and analysis tools to analyze very large and complex genetics data for meaningful results.
   • The Kids First Data Resource, and associated computational tools, will be developed with ease of use in mind. This will enable a wide variety of researchers to access and use the data, not just a small subset with specialized training in sophisticated bioinformatics techniques. Enhancing the usability of the data will accelerate progress by ensuring many highly creative and dedicated scientists have the ability to investigate important research questions about pediatric conditions such as childhood cancer and structural birth defects.
   
   The Kids First Data Resource is expected to stimulate research and potentially accelerate the development of more effective preventions and therapies for diverse conditions. The nature of scientific research and discovery makes it difficult to predict when such therapies may be widely available, but the Kids First program will build a strong foundation to enable development of therapies that might not otherwise be possible.


7. Will there be additional opportunities for sequencing structural birth defects and cancer cohorts that were not initially selected for sequencing?
   
   Yes, the Kids First program plans to support sequencing of additional childhood cancer and structural birth defects cohorts in 2017, 2018, 2019, and possible beyond, pending the availability of funds. Researchers interested in proposing their cohorts for sequencing should check the Kids First website and sign up for the Kids First listserv to receive program updates. Anyone interested in pediatric research can help by letting researchers know about Kids First and the ability to apply to have their childhood cancer and/or structural birth defects cohorts whole genome (DNA) sequenced. They can also help bring together multiple researchers with small cohorts and encourage them to collaborate to increase the cohort size.


8. How can I stay up-to-date on Kids First program activities?
   
   Updates on program activities will be posted to the Kids First website. Individuals wishing to receive program updates may also sign up for the Kids First listserv. Examples of what you can expect to receive via the listserv include new funding opportunities, information on awardees and their proposed research, and summaries of exciting research findings from the Kids First program.


9. In addition to the Kids First program, what is NIH doing to support pediatric research?
   
   Pediatric research is a major focus of NIH research. In fiscal year 2014 – before Kids First – the NIH funded a total of approximately $3.5 billion in research grants and projects directed specifically at pediatric research. Of the 27 NIH Institutes and Centers (ICs), 25 of them support pediatric research. The National Institute of Child Health and Human Development (NICHD) is the primary NIH Institute that supports pediatric research, including structural birth defects. The National Cancer Institute (NCI) is dedicated to promoting cancer research from exploring the causes of cancer to new diagnostics, preventions, and treatments. Childhood cancer research is one of NCI’s dedicated areas of research.
   
   The Kids First program will be a new tool that leverages the research being funded by NICHD, NCI, and other NIH ICs to stimulate research and potentially accelerate the development of more effective preventions and therapies for diverse conditions.