Scientists studying the human brain have long faced a complex obstacle: because of the scarcity of neurotypical human brain tissue, tissue samples from a single brain must be shared across research entities. Those entities then generate massive amounts of data from their research, but often lack a coordinated way to share, combine, or reuse the information.
To solve this problem, a team of UTHealth Houston researchers led by GQ Zhang, PhD , vice president and chief data scientist at UTHealth Houston, has developed a data platform that is a "digital twin" of the research workflow. This new technology has allowed scientists to track brain health research from the moment a tissue sample is taken to the resulting scientific data. The technology is used within the National Institutes of Health's BRAIN Initiative® Cell Atlas Network, or BICAN, a large national collaborative research network.
"You first have the physical part, which is where the lab takes the resources and transforms the tissue all the way to data. A dozen or more labs are involved in the physical process," said Zhang, who is the corresponding author of the research and a professor in the Department of Health Data Science and Artificial Intelligence at McWilliams School of Biomedical Informatics at UTHealth Houston. "For the digital twin, we have a way of mirroring exactly what physical process is taking place: who received what piece of tissue and performed what on that tissue, where they sent it to get sequenced, and where the sequenced datasets get deposited. Our system manages the entire 15 steps between the tissue and the data."
The research was published today in Cell Genomics .
The new technology, called the Neuroanatomy-anchored Information Management Platform, or NIMP, also allows scientists to track details such as what region of the brain a tissue sample came from and demographic information about the corresponding donor.
"You can think of the digital twin as a financial bank for this purpose," said Zhang, who is also co-director of the Texas Institute for Restorative Neurotechnologies, professor in the Department of Neurology at McGovern Medical School at UTHealth Houston, and the medical school's Distinguished Chair in Digital Innovation. "If you don't have records of funds-transfer wires, ledgers, and transactions, it's an entire mess of who spent money on what account. The NIMP is as disciplined as a banking system for the NIH BRAIN Initiative."
BICAN is an international collaborative project in which scientists from 55 institutions across nine countries are aiming to create a defining, evolving atlas of cell types across human, macaque, marmoset, and mouse brains.
Zhang is a principal investigator on a BICAN project and corresponding author of two papers published today that are among a collection of more than two dozen research papers on the basal ganglia.
This publication package represents a part of BICAN's first three years of work, setting the foundation for how scientists will map the rest of the brain using the same methods. The other paper authored by Zhang and his team, in collaboration with BICAN, is published in Cell and is the flagship paper in the package, which details the scope and significance of the collaboration.
The basal ganglia constitute one of the brain's most clinically significant neural systems, playing central roles in motor control, cognition, motivation, and reward processing. Dysfunction of basal ganglia circuits is implicated in a broad spectrum of neurological and neuropsychiatric disorders, including Parkinson's disease, Huntington's disease, obsessive-compulsive disorder, and addiction.
NIMP focuses on human brains and brains of other species and contains data and metadata from 762 human donors and more than 8,000 brain tissue samples. More than 18 million cells in the basal ganglia are tracked through the NIMP platform.
The project has the potential to do for brain health what the Human Genome Project did for precision medicine, Zhang said.
"Just as the Human Genome Project transformed our understanding of human genetics, BICAN has the potential to revolutionize our understanding of the human brain," Zhang said. "NIMP serves as a cornerstone of this effort, providing the essential infrastructure to track, connect, and integrate the vast amounts of tissue and data generated across participating laboratories."
Authors from UTHealth Houston on Zhang's digital twin research include: Shiqiang Tao, PhD; Xiaojin Li, PhD; Yan Huang, PhD; Rashmie Abeysinghe, PhD; Ling Tong, PhD; Erge Edgu-Fry, PhD; Wei-Chun Chou, MS; Licong Cui, PhD; and Shiwei Lin, MS. Additional authors include Kimberly A. Smith, BS; and Lydia Ng, PhD, of the Allen Institute.
In addition to UTHealth Houston, the BICAN consortium includes: Allen Institute; Broad Institute of MIT and Harvard; Salk Institute; University of California, San Francisco; University of California, Los Angeles; Harvard University; and UT Southwestern Medical Center.
