By Maxine Bookbinder

January 25, 2022 | After a decade of methodical preparation, Canada’s Ontario Brain Institute's (OBI) neuroinformatics platform, Brain-CODE, launched its open data sharing feature for global brain disorder research.

Brain-CODE, the data side of OBI, is a neuro-informatics platform designed to support data capture, sharing, storage, analysis, and release. It enables external researchers locally and globally to collaborate and build on OBI researchers’ existing data, explore causes of brain disorders, and find new therapies.

“The novel research and the Brain-CODE platform that will help amplify these data on a global scale are remarkable, particularly for the nearly one in six people suffering from neurodegenerative diseases worldwide,” says Richard Swartz, M.D., co-lead of Ontario Neurodegenerative Disease Research Initiative (ONDRI).

Tom Mikkelsen, M.D., OBI President & Scientific Director, describes Brain-CODE as “a way of doing business, a data eco-system.” It is a clinical interface—from how data are gathered to the way they are standardized, entered into an organized format, curated, quality ensured, and then shared—rather than a simple data base.

OBI has conducted research and clinical trials for 10 years in epilepsy, cerebral palsy, neurodegenerative diseases, neurodevelopmental disorders, depression, and concussions. These results, which have been loaded into Brain-CODE over the years, were available only to OBI researchers; now, scientists globally have access to this abundance of unique data.

“Most organizations study a single disease,” says Mikkelsen. “We have a whole life span range of disorders. We study the intersection of different neurologic diseases. We study the influence of concussions on depression. Parkinson’s Disease researchers don’t study sleep disorders. We do all of that.”

Through their foundational study, Swartz and the team at ONDRI examined the genes of 520 participants with various diseases, such as Parkinson’s Disease (PD), Alzheimer’s Disease (AD), frontotemporal dementia (FTD), cerebrovascular disease (CVD), and amyotrophic lateral sclerosis (ALS). They discovered that CADASIL, a genetic small-vessel brain disease associated with dementia, headache, and stroke, was found in 15-20% of participants with PD; this association has never been described before. “The whole point was to look at genes in one group to see if they are expressed in another, looking at genetic anomalies across the cohort,” says Swartz. “Our researchers found this on purpose by accident.” The discovery, he says, may be a new, previously unknown risk factor for developing PD.

“This is only possible because we are looking across diseases through ONDRI’s research,” says Swartz. “We tested a gene we know causes CVD in people with Parkinson’s, not CVD. We are looking at the gene expressed in one group to see if it is expressed in other groups.”

The traditional custom of keeping clinical trial results secret has given way to the practice of “collect once and use many times,” says Mikkelsen. It throws open the door to new research worldwide by experts who can read these data, build on them with their own data, and compare results and methodologies. Other scientists can then see those additional conclusions and continue to build from the original OBI data.

“If data can benefit people more broadly, then why wouldn’t we do this?” Says Mikkelsen. “The data is provided by participants in the hope that someday they will make life better for the people who come after them.”

OBI initiated its open data platform with carefully planned precautions to ensure confidentiality. All patient information is de-identified; names and records are stripped and encoded. Data are cleaned to ensure that the participant’s identity cannot be discovered. For example, MRI scans, which contain facial identification, go through significant processing, called defacing, to remove identifying features to ensure anonymity.

All data are shared in a controlled way; primary sources stay on the Brain-CODE analytics platform and cannot be downloaded. However, researchers can bring their own data into the platform, compare their patients’ MRI scans with the scans on Brain-CODE, and take away their own analyses, results, and statistics.

OBI abides by the Findability, Accessibility, Interoperability, and Reusability (FAIR) principles for data-sharing. Before potential viewers can access information, they must file an inquiry and complete an application (with an Institutional Review Board in the U.S. or Research Ethics Board in Canada) to verify they are researchers at reputable institutions requesting data for a project vetted by that jurisdiction. Once this information is verified by an oversight committee, the applicant can create an account and is then granted access.

“We want to make it as easy as possible [to view data] without too many constrictions,” says Mikkelsen. “We want to have a balance in the environment in which we can innovate. This is a global opportunity to move the needle on neurological disorders.”

Mikkelsen notes that OBI researchers, as well as scientists worldwide, are motivated investigators who test hypotheses, share discoveries, innovate in their fields, and ultimately create life-saving breakthrough discoveries. Although all primary data on OBI’s Brain-CODE platform are the product of OBI investigators, whatever new discoveries evolve from them belong to those scientists; OBI researchers do not take credit for subsequent, new findings by others.

“Data are not knowledge; knowledge comes from the analysis of data,” says Mikkelsen. We don’t presume to take a piece of someone else’s discovery. We are interested in a data-sharing community that brings its own derivatives onto the platform and builds from there. It’s sort of a global brain on these problems.”

Just as scientists dedicate themselves to discovery, Mikkelsen notes it is important to recognize the contribution of the clinical trial participants, who are “the people who invest significant time, energy, and emotional capital to contribute to ground-breaking research.”

These participants have, in a sense, become pioneers, living with autism, dementia, and other neurological diseases during Covid. OBI researchers adapted to their needs while continuing clinical trials by accommodating participation in their homes. For example, in ONDRI’s new Health in Aging, Neurodegenerative Diseases and Dementias in Ontario (HANDDS-ONT) study, coordinators are mailing wearable monitoring devices to participants, who wear and then mail them back. Participants also self-report outcomes on surveys at home and complete telemedicine visits. These study protocol changes may be permanent. “Even before Covid we were moving toward gathering data from participants living in their homes and communities and not just from the clinic,” says Swartz. “This better reflects people’s lives and how they manage their diseases in the real world.”

OBI staff are moving forward, planning what the next generation platform will look like. High performance computing infrastructure will include Artificial Intelligence (AI) and machine learning (ML) to allow continuous algorithms rather than intermittent releases. Because ML is dependent upon large amounts of data, much more is needed. “It’s too soon to say we’ve hit a home run,” says Mikkelsen. To address this need while upholding its commitment to an open science concept, OBI is collaborating with like-minded international scientists conducting research in similar ways.