Upgrade 2021: CIS LAB Speakers

September 21, 2021 // Upgrade 2021: CIS LAB Speakers

Using Digital Twin Technology to Find the Needles in the Alzheimer’s Research Haystack

Cory Funk, Senior Research Scientist | Institute for Systems Biology

Summary

Alzheimer’s disease has been particularly vexing for medical researchers for a number of reasons, including the fact that genome-wide studies have identified more than 40 genetic loci associated with the disease. But digital twin technology presents a promising way to break down the challenge into smaller components, eliminate some possibilities, and find the path to a cause on an individualized basis.

Dr. Cory Funk is focused on Alzheimer’s in his role as a Senior Research Scientist at the Institute for Systems Biology, a nonprofit biomedical research organization based in Seattle. In a talk at Upgrade 2021, Dr. Funk reported on his work with digital twins to “reduce the hypothesis space by means of causal reasoning.” It’s an important endeavor because there is so much variability in how the disease manifests itself, with the same inputs appearing to cause Alzheimer’s in some individuals but not others.

These variations contribute to what makes Alzheimer’s research so difficult, resulting in more than 400 failed clinical drug trials, at a cost of upwards of $200 million per trial, Dr. Funk said. On top of that, Alzheimer’s is expected to consume vast resources from Medicare and Medicaid in coming decades. “So there really is a huge economic burden with Alzheimer’s,” he said.

In terms of research, the problem stems from the lack of a causal framework that can help researchers understand what causes Alzheimer’s in any individual patient. “We can make generalizations about them, but for a single person, it’s really hard to understand mechanistically what’s going on,” Dr. Funk said.

The solution lies in creating functional processes that model pathways within the brain as sort of an intermediary step. Those pathways can be modeled with digital twin technology. At that point, researchers can then connect various genomic factors with the functional processes, and eliminate some confounding factors along the way. “You’re breaking down the problem,” he said.

“This is sort of the basis of how we could potentially personalize medicine, if we can bridge this gap and can understand those genomics and how they relate to those functional processes,” Dr. Funk said.

To date Alzheimer’s research is quite fragmented, with few if any organizations trying to integrate all known nuggets of causal reasoning into a full model. But that’s the idea behind the EmbodyBio Brain Health and Neurodegeneration model, a digital twin model for use by Alzheimer’s researchers, among others.

“EmbodyBio has created a model and they’ve broken it up into 13 different subsystems,” he said. “They based it on over 500 references, so really scouring papers for the biology and trying to capture that biology within their model.”

With such a model, researchers can now look at the risk factors that might contribute to Alzheimer’s over the 25 years or so during which the disease develops and progresses. “You’ve got to be able to model basically the entire lifetime of an individual if you want to understand Alzheimer’s,” Dr. Funk said.

To learn more about his research view the full video of his talk above, or click below for a transcript.

Presented at the NTT Research Upgrade 2021 Summit on September 21, 2021.

 

Click below for the full transcript.

Cory Funk

Senior Research Scientist | Institute for Systems Biology

Dr. Funk is a Senior Research Scientist at The Institute for Systems Biology in Seattle, Washington. Dr. Funk received his PhD from the University of Illinois Urbana-Champaign in Cell and Developmental Biology where he trained as an experimentalist and studied the role of the estrogen receptor in gene transcription in breast cancer. He joined Nathan Price’ group as a postdoc, moving to Seattle, turning his focus to transcriptional regulation in glioblastoma and other brain tumors. Dr. Funk transitioned to computational biology, working within the NIH Accelerating Medicines Partnership in Alzheimer’s Disease (AMP-AD) beginning in 2014, with a focus on the role of innate immunity and metabolism in AD. Building on his interest in transcriptional regulation of the estrogen receptor, Dr. Funk has utilized genome-scale transcriptional models from post mortem brain samples to help identify key drivers of transcription in AD. Dr. Funk also is investigating the putative role of herpes virus as a contributor to AD pathophysiology. Dr. Funk currently works with Dr. Leroy Hood, along with many other collaborators, in efforts to integrate longitudinal -omics data sets for the purpose of understanding AD etiology.