Project Singular: Building a Large-Scale Genetics Dataset to Fuel Research Towards Curative Solutions for Single Ventricle Heart Disease
Presented By:
Diane M. Pickles, Program Director, Project Singular, Additional Ventures; Kirstie E. Keller, PhD, Vice President of Programs, Additional Ventures
Additional Ventures
dpickles@additionalventures.orgOverview:
Background: Single ventricle (SV) heart disease is a set of rare conditions occurring in 5 out of 100,000 births with significantly decreased duration and quality of life. The cause of SV heart disease is unknown but believed to be multigenic and multifactorial. Several genes have been linked to SV disease; however, the penetrance in model organisms is low and none are thought to be causal, and the relationship between genetics and outcomes is unclear. Project Singular aims to uncover the cause(s) of SV and related sequalae by creating the largest genetic dataset available to date in this disease community.
Methods: At least 5,000 SV patients and immediate family members are recruited and consented virtually and receive a biospecimen collection kit (saliva or buccal) by mail to return to the Broad Institute of MIT and Harvard. Samples are processed, quality-controlled, and whole genome-sequenced using Illumina HiSeq at 30X coverage, with methylation arrays conducted on a subset. Sequences are then aligned to the human genome, annotated, deidentified, and securely deposited into the Terra.bio platform. Participants respond to a survey on demographics and medical history, and patients provide medical records. Specific clinical data is extracted and entered in the registry management system.
Results: The online portal launched end of May 2022 to a small group of potential participants. To date, 20 individuals have completed enrollment; 8 of these are patients [6 adults, 2 minors] and 12 are family members [8 birth parents, 3 siblings]. There are 5 family cohorts enrolled. Of these, 3 families consist of 2 parents, an affected child, and an unaffected sibling, and 2 family cohorts consist of a parent and an unaffected child. No sequencing has yet been finalized. A comprehensive recruitment strategy is planned for Fall 2022 which includes promotional materials distributed via clinics, organic and paid social media, and outreach via patient advocacy and support organizations. Deidentified phenotypic and genotypic data will be made available for free to qualified researchers globally. Integration with other SV-related registries will be undertaken where possible to increase the power of the study.
Conclusion: Project Singular is the first genetics sequencing initiative of its size and depth focused specifically on SV, the most complex of all congenital heart defects. By enabling patients and families to participate from their homes, Project Singular reduces barriers of travel and cost to increase diversity of participants. Data democratization of the dataset will fuel discovery in SV and related sequalae etiology, leading to new targeted treatments and potentially curative solutions.
Methods: At least 5,000 SV patients and immediate family members are recruited and consented virtually and receive a biospecimen collection kit (saliva or buccal) by mail to return to the Broad Institute of MIT and Harvard. Samples are processed, quality-controlled, and whole genome-sequenced using Illumina HiSeq at 30X coverage, with methylation arrays conducted on a subset. Sequences are then aligned to the human genome, annotated, deidentified, and securely deposited into the Terra.bio platform. Participants respond to a survey on demographics and medical history, and patients provide medical records. Specific clinical data is extracted and entered in the registry management system.
Results: The online portal launched end of May 2022 to a small group of potential participants. To date, 20 individuals have completed enrollment; 8 of these are patients [6 adults, 2 minors] and 12 are family members [8 birth parents, 3 siblings]. There are 5 family cohorts enrolled. Of these, 3 families consist of 2 parents, an affected child, and an unaffected sibling, and 2 family cohorts consist of a parent and an unaffected child. No sequencing has yet been finalized. A comprehensive recruitment strategy is planned for Fall 2022 which includes promotional materials distributed via clinics, organic and paid social media, and outreach via patient advocacy and support organizations. Deidentified phenotypic and genotypic data will be made available for free to qualified researchers globally. Integration with other SV-related registries will be undertaken where possible to increase the power of the study.
Conclusion: Project Singular is the first genetics sequencing initiative of its size and depth focused specifically on SV, the most complex of all congenital heart defects. By enabling patients and families to participate from their homes, Project Singular reduces barriers of travel and cost to increase diversity of participants. Data democratization of the dataset will fuel discovery in SV and related sequalae etiology, leading to new targeted treatments and potentially curative solutions.
