SAN FRANCISCO — By fusing the power of artificial intelligence with new molecular techniques that also seem straight out of science fiction, UCSF researchers have mapped the microscopic world of autism spectrum disorder in unprecedented detail, pointing toward potential therapies for a subset of patients who have specific characteristics. Genetic mutations, according to a new study.
“This opens up a sort of Goldilocks of potential treatment targets,” said one of the study’s authors, Matthew State, a child psychiatrist and geneticist at UCSF. “It’s an opportunity to shoot on goal that we haven’t had before, due to the complexity of autism.”
The results are novel for several reasons, the researchers said. It is the first time that the cellular functioning of a neuropsychiatric disorder such as ASD has been explored so deeply, opening the door to similar investigations of other neuropsychiatric disorders such as attention deficit hyperactivity disorder and schizophrenia.
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The studio also uniquely combined a basket of new technologies. Those technologies include stem cells, CRISPR-based genetic tools, and AlphaFold 2, Google’s AI that predicts protein behavior.
Additionally, the researchers took advantage of a system originally developed at UCSF to study viruses, including the coronavirus that causes the pandemic. This platform is capable of creating complete maps of the interactions between proteins, the biological machines produced by genes that carry out work in the cell.
“We’ve been at the forefront of putting this all together,” said another study leader, Nevan Krogan, director of the Institute for Quantitative Biosciences at the UCSF School of Pharmacy, which coordinated the research along with the Department of Psychiatry and Human Sciences. of Behavior.
The paper was posted Monday on bioRxiv.org, a preprint server, and will be submitted to a peer-reviewed journal. Jeremy Willsey and Tomasz Nowakowski of UCSF co-led the work, and Rezo Therapeutics, a biotechnology company founded by QBI and Krogan, also contributed.
Over the past decade, scientists, including State, have discovered more than 100 mutated genes that are linked to autism. But translating that knowledge into therapies has been difficult, State said. The brain is complex and knowing the right genes is not enough.
The UCSF-led team took a new approach, focusing on the proteins made by those genes and mapping how they interact with each other.
The researchers found 1,000 proteins and more than 1,800 interactions. About 90% of the interactions “are things we’ve never seen before,” State said.
The team then looked for clues about how the mutations lead to the disorder by using mutations specific to a subset of people with ASD. The scientists exploited the predictive capabilities of AlphaFold and various molecular techniques to identify the most significant interactions, studying how these proteins function in human cells and in “brain organoids” grown from stem cells.
These findings could one day lead to new medications for patients, State and Krogan said.
“We are shedding new light on autism,” Krogan said.
© 2023 San Francisco Chronicle
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