PPMI RNA-Sequencing, the Largest Dataset of Gene Activity in Parkinson’s, Now Available to Researchers

The largest dataset ever compiled on Parkinson’s disease research — equivalent to 47.5 billion single-spaced typed pages — is now available to scientists, and can be used to investigate genetic changes over time in people with the neurodegenerative disorder.

Funded by the Michael J. Fox Foundation, the “Parkinson’s Progression Markers Initiative (PPMI) RNA-Sequencing Project” can help researchers assess how genetic changes observed in Parkinson’s impact disease progression or response to medication.

The study was led by Kendall Van Keuren-Jensen, PhD, at the Translational Genomics Research Institute (TGen), and David W. Craig, PhD, at the University of Southern California (USC).

A team of researchers analyzed samples obtained exclusively from the MJFF-sponsored Parkinson’s Progression Markers Initiative (PPMI), the most comprehensive study on PD until now. The PPMI study included more than 4,750 anonymous samples from 1,589 people with clinical and genetic PD risk factors and healthy control volunteers.

“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,” Todd Sherer, PhD, the Foundation’s CEO, said in a press release.

Using a technique called RNA sequencing, researchers were able to analyze the entire RNA content of the PPMI samples. Analyzing the data — containing more than 108 terabytes of raw and processed sequencing data — took 480,000 hours of processing time, the researchers said.

All genetic information contained within genes, known as DNA, is ultimately translated into proteins. However, several complex steps exist before a protein can be produced. DNA is first transformed into RNA, after which a process called translation begins. That process gives rise to proteins.

By comparing the RNA levels of people with PD and controls, researchers can get a deeper understating of the key genes that play a role in the disease — and how their activity changes over time.

“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, co-director of the Center for Noninvasive Diagnostics at TGen, an affiliate of City of Hope.

“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,” Keuren-Jensen added.

The RNA-sequencing data from the PPMI project is accessible to all researchers, who first need to apply for access through the PPMI website.

“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 of the Institute of Translational Genomics at Keck School of Medicine of 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 researchers better understand Parkinson’s, its variability, and ways to measure and treat it, the MJFF said.