People with amyotrophic lateral sclerosis (ALS) face progressive loss of the motor neurons that control their muscles, eventually leading to paralysis and death. While researchers have uncovered some of the underlying mechanisms of this devastating disease, no treatment can yet halt it.
Now, an initiative called Answer ALS has launched its new, open-sourced data portal to provide researchers worldwide with access to comprehensive biological and clinical data from over 1,000 people with ALS.
“A publicly available dataset of this size is completely unprecedented for ALS,” says Steve Finkbeiner, MD, PhD, director of the Center for Systems and Therapeutics at Gladstone Institutes who has partnered with Answer ALS to lead crucial contributions to the portal.
Scientists, companies, and other interested parties can use the portal to access a growing trove of clinical, genomic, transcriptomic, metabolomic, and epigenomic sequence data from every participating patient.
“We envision these data laying the foundation for machine-learning and artificial-intelligence analysis that could provide new insights into the mechanisms of ALS, and ultimately, enable new treatments,” Finkbeiner says.
His lab is responsible for several key components of the project, including generating whole-genome sequence data for each participant. Nearly all participants have now had their genomes sequenced and incorporated into the portal.
Finkbeiner’s team is also using participants’ donated tissue samples to generate induced pluripotent stem cells (iPS cells) from which motor neurons can be grown. Then, by using robotic microscopy, they are generating data that will enable portal users to analyze the differences between healthy motor neurons and those from people with ALS.
“This will allow us to build bridges between the phenotypes of cells we can measure in a dish and the clinical features of the patients from whom those cells came,” Finkbeiner says.
He and his partners at Answer ALS are particularly excited for the potential of the new portal to enable distinction between subgroups of ALS patients whose disease may result from different underlying molecular mechanisms.
“Finding signs that differentiate subgroups of ALS patients could lead to ways of designing drugs that are specifically tailored for each subgroup,” Finkbeiner says.
In collaboration with another Answer ALS research partner, Finkbeiner’s lab is already using artificial intelligence and other computational strategies to sift through the data and search for patterns that could reveal promising new treatment strategies.
“It is my lifelong ambition to move beyond current concepts about disease modeling that mostly focus on parroting disease features and instead work toward a preclinical pipeline that predicts results in patients,” Finkbeiner says.
The Answer ALS Data Portal grew out of a program initially seeded by the National Institutes of Health and is now fueled by Microsoft and philanthropy. It is also supported by the Stephen Hawking Foundation, which honors the renowned physicist who lived with ALS for many years.
By opening up the portal to the entire research community, Answer ALS hopes that scientists and artificial intelligence experts who do not have the resources to generate their own datasets will nonetheless have the opportunity to apply their creativity and generate new ALS knowledge.
“Gladstone has long been a leader in ALS research, and this is an incredible next step for the field,” says Gladstone President Deepak Srivastava, MD. “Thanks to Steve and other Answer ALS partners, this project holds real potential to transform ALS research and treatment.”
An 8-year-old with CMT meets with Gladstone researchersGladstone Experts Conklin Lab