- The “PPMI RNA-Sequencing Project” provides unprecedented insights into how gene expression changes over time in people with Parkinson’s disease. At 108 terabytes, the project is the largest disease-focused data set ever created.
- Combined with other data collected from studies sponsored by The Michael J. Fox Foundation, this project can illuminate the genetic drivers of Parkinson’s and the underlying mechanisms that lead to the development and progression of the disease.
- Researchers can access the data set through a portal at www.ppmi-info.org.
August 20, 2019 – NEW YORK, NY – The Michael J. Fox Foundation for Parkinson’s Research (MJFF) today announces the release of the largest data set in disease research. The “Parkinson’s Progression Markers Initiative (PPMI) RNA-Sequencing Project” is a massive RNA sequencing study funded by MJFF and led by Kendall Van Keuren-Jensen, PhD, at The Translational Genomics Research Institute (TGen), an affiliate of City of Hope, and David W. Craig, PhD, at the University of Southern California (USC).
Data from the new study can be used to explore genetic changes associated with Parkinson’s and the impact of gene expression on factors including age, disease progression and even medication use. Analysis of these data could help the field better understand Parkinson’s, its variability and ways to measure and treat it.
The Largest Disease-focused Data Set Ever Created
The data set contains more than 108 terabytes of raw and processed sequencing data. It is equivalent to 47,520,000,000 single-spaced typed pages, and analyzing the data took 480,000 hours of processing time. The PPMI RNA-Sequencing Project team exclusively used samples from the MJFF-sponsored PPMI — a landmark study that has united the Parkinson’s field around the search to identify and validate Parkinson’s biomarkers. The project included collaboration with Mark Cookson and other researchers at the National Institute on Aging; and RNA sequencing was conducted by HudsonAlpha Institute for Biotechnology.
“PPMI has built the most robust Parkinson’s data set to date, collecting clinical, imaging and biological information from volunteers over at least five years to better understand disease onset and progression. The PPMI RNA-Sequencing Project significantly increases the study’s value and moves us closer to its goals to better define, measure and treat Parkinson’s disease,” said Todd Sherer, PhD, MJFF CEO.
RNA sequencing measures the diversity and quantity of RNA in a biological sample at a given time point, allowing for observation of potentially meaningful changes in the expression of genes. The PPMI project analyzed more than 4,750 de-identified samples from 1,589 people across cohorts with clinical and genetic Parkinson’s risk factors, idiopathic and genetically implicated patients and control volunteers.
“Mutations in genes can affect proteins in ways that contribute to Parkinson’s disease, but that’s only part of the picture. To understand all the causes of the disease, we need reliable data on as many molecular measurements as we can: DNA, RNA and resulting proteins,” said Van Keuren-Jensen, Professor, Neurogenomics Division and Co-Director, Center for Noninvasive Diagnostics at TGen, an affiliate of City of Hope. She adds, “RNAs function as messengers from genes to create proteins, and many types of RNA have additional roles in cells that we are just beginning to understand. We sequenced these samples to capture as many types as possible, including protein-coding genes, lncRNAs and circular RNAs.”
In order to increase the diversity and scope of the RNAs captured in this project, the small RNA species were also sequenced. Andreas Keller, PhD, of Saarland University and Hummingbird Diagnostics, is leading the integration of these data.
A Portal for the Researcher Community to Expand Parkinson’s Understanding
The PPMI RNA-Sequencing Project analyzed samples collected at consistent intervals using standardized collection methods, reducing sources of bias in the data. Sequencing followed strict protocols to ensure the same standards of consistency and reliability. The RNA-sequencing data can be used in conjunction with PPMI’s robust genetic, clinical, biological and imaging data on the same volunteers. This creates a “one-stop shop” solution for researchers and can be used to generate a better understanding of the genetic drivers of Parkinson’s and the biological mechanisms underlying its development, onset and progression. Additionally, the depth and quality of this data set may provide insights beyond Parkinson’s and establish a roadmap for similar studies targeting other diseases.
“Through PPMI, the Fox Foundation has created an unprecedented resource for the research community. And this RNA sequencing project is bringing another layer of information to explore and compare toward greater understanding of the disease and how to stop it,” said Craig, Professor of Translational Genomics and Co-Director, Institute of Translational Genomics at Keck School of Medicine of USC.
The PPMI RNA-Sequencing Project data can be accessed through a portal, developed by the Van Keuren-Jensen and Craig labs, and made available through the PPMI study site at the Laboratory of Neuro Imaging at the University of Southern California (LONI), part of the USC Mark and Mary Stevens Neuroimaging and Informatics Institute. The portal provides overviews of RNA data generated from raw sequencing reads of PPMI samples, made-to-order tables from the full data set, and includes a visualization tool. This tool lets users observe changes in gene expression for each gene transcript present in the human genome, including distinction across cohorts and disease states. This allows for rapid survey of genes of interest, supporting detailed analysis and hypothesis testing. Researchers can apply for access at the PPMI website:
About The Michael J. Fox Foundation for Parkinson's Research
As the world's largest nonprofit funder of Parkinson's research, The Michael J. Fox Foundation is dedicated to accelerating a cure for Parkinson's disease and improved therapies for those living with the condition today. The Foundation pursues its goals through an aggressively funded, highly targeted research program coupled with active global engagement of scientists, Parkinson's patients, business leaders, clinical trial participants, donors and volunteers. In addition to funding more than $800 million in research to date, the Foundation has fundamentally altered the trajectory of progress toward a cure. Operating at the hub of worldwide Parkinson's research, the Foundation forges groundbreaking collaborations with industry leaders, academic scientists and government research funders; increases the flow of participants into Parkinson's disease clinical trials with its online tool, Fox Trial Finder; promotes Parkinson's awareness through high-profile advocacy, events and outreach; and coordinates the grassroots involvement of thousands of Team Fox members around the world.
The Michael J. Fox Foundation