Scientists at Washington University School of Medicine in St. Louis are joining a national network to map the intricacies of the brain, with the goal of deepening our understanding of how the brain works and gaining new insights into how the brain works works in healthy people – and how it doesn’t work in Alzheimer’s, schizophrenia, autism and numerous other diseases.
The new network, called BRAIN Initiative Cell Atlas Network (BICAN), is supported by the National Institutes of Health (NIH). Efforts are focused on mapping the human brain, but are also extending to the brains of non-human primates and mice, so researchers can see similarities and differences between species and better understand the molecular and cellular mechanisms underlying brain function.
The Washington University grants will fund portions of two separate projects. One is being led by the Allen Institute for Brain Science in Seattle, Washington, and is building a global collaboration to map the 200 billion cells in the human brain by type and function. At Washington University, David C. Van Essen, PhD, the alumni endowed professor of neuroscience, and Matthew F. Glasser, MD, PhD, an associate professor of radiology at the university’s Mallinckrodt Institute of Radiology, will create brain maps of individual humans and analyze nonhuman primates to determine the types of cells that make up each brain area using data collected from humans and animals scanned at collaborating sites.
The second project, led by the Salk Institute for Biological Studies in La Jolla, California, aims to describe brain cells in unprecedented molecular detail, classify such cells into more precise subtypes, determine and track their locations in the brain, how the aging process can affect these properties. Ting Wang, PhD from Washington University, Sanford C. and Karen P. Loewentheil Distinguished Professor of Medicine, will manage and analyze the project’s vast genomic datasets with collaborators at the University of California, San Diego and the University of California, Irvine .
Individualized brain maps
Van Essen and Glasser’s work for BICAN builds on the Human Connectome Project, a large-scale project led by Van Essen to map the connections in the human brain. Using methods developed for the Human Connectome Project and data from 210 people, Glasser and Van Essen identified 180 areas in each half of the cerebral cortex, which is the dominant structure of the human brain and is largely responsible for the functions that make us unique make human . They also developed machine learning methods to automatically map these areas in people using MRI data.
“The BICAN grant will add a tremendous amount of information to this brain map about which genes are active and where they are active and how they are coordinated and integrated,” said Van Essen. “This will essentially give us a much richer characterization of what makes one area or part of the brain different from another. Having this information for people without brain disorders will provide a basis for studying brain disorders like autism and schizophrenia, which we know have a genetic component, but we don’t understand how genes contribute to the disorder.”
As part of the new study, Van Essen and Glasser will analyze data from people who voluntarily donate their brains for research. As soon as possible after death, the brain is scanned by MRI and gene expression in the brain cells is measured. In some cases, the researchers also have data from functional brain scans taken while the study participant was alive.
“The excitement surrounding this project is reminiscent of our beginnings with the Human Connectome Projects over 10 years ago,” said Glasser. “Now we are taking the next step by integrating cell and systems neuroscience. We will combine cellular-level genetic mapping with functional mapping of, for example, the language and visual systems to generate rich data that could advance research into all types of brain diseases.”
Brain Atlas Informatics
Wang is an expert on the epigenome, or the instructions that determine how genes are turned on or off in a given cell. He is part of a project to analyze the epigenetics of 1,500 brain samples from people of different ages, and Wang is tasked with managing the vast genomic datasets and developing new computational methods to analyze that data.
“The scale of data production will be light years beyond anything we’ve done in the past,” Wang said. “So far we have processed hundreds of thousands of data sets. Now we’re talking about millions. We will also use our experience in analyzing the epigenomes of other cell types, including for example cancer cells, to create a detailed, comprehensive and high-resolution map of the human brain and how it works at the single-cell level. ”
Wang and his colleagues have developed what they call the WashU Epigenome Browser, an online tool that researchers can use to search for information and data characterizing the epigenomes of many species, such as fruit flies, mice and various primates, including humans. The browser also contains some protozoa and the genomes and epigenomes of viruses, including Ebola and SARS-CoV-2.
“We plan to develop many technical innovations in web technology, browser development, as well as machine learning-based analysis tools so that we can make this data much easier for researchers who want to use it,” Wang said.