3-D map of mouse brain gene expression

The brain atlas details more than 21,000 genes at the cellular level.

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SEATLLE—Three years and $41 million in the making, found­er Paul Allen and scientists of the Allen Institute for Brain Science recently unveiled their first ground-breaking achieve­ment: a three-dimensional map of gene expression in the mouse brain. The brain atlas, made publicly available at launch with no cost to researchers, details more than 21,000 genes at the cellular level and data that were previously unavailable to the scientific community.
With mice and humans shar­ing roughly 90 percent of the genes in both species, the hope is that the mouse brain map will aid researchers not only in understanding the role of genes in basal brain function, but will also provide new insights into the location and roles of spe­cific genes in a host of human disorders including Alzheimer's disease, Parkinson's disease, epilepsy, schizophrenia, autism and addiction.
"This is a new way of mapping the brain that reveals its hidden genetic resources," says Dr. David Anderson, professor of biology and Howard Hughes Medical Institute investigator at the California Institute of Technology. "Before the Atlas, a student would have to spend years just prospecting, as it were, before they could even begin to address their [scientific] ques­tion. Now the prospecting has been done for them.
"In the same way the Human Genome Project identified and sequenced genes for us, this has done the same thing for neurosci­ence and is every bit as important and epoch-making as the genome project has been for molecular genetics."
One finding of the project was the revelation that 80 percent of genes are turned on by the brain, a significantly higher percentage than the 60 to 70 percent scien­tists previously believed. Further, it showed that very few genes are turned on in only a single region of the brain—a finding that could have implications regarding the benefits and potential side effects of drug treatments.
At the time of the official announcement, Allen Institute researchers indicated that the atlas was already being accessed by more than 250 visitors a day, many of them from major pharmaceuti­cal companies.
"We like to say that this is a gift of time to researchers around the world," says Allan Jones, CSO of the Allen Institute and the person who managed the three-year proj­ect. "We've done the experiments for them, so they can spend their time and resources following up on the questions they pursue in any number of disease areas."
In undertaking the project three years ago, the Allen Institute assembled an interdisciplinary team of researchers and scientists more than 80 strong. Expertise of team members ranged from neuroscientists and biologists to software engineers, architects and software developers.
"We then needed to apply these [resources] with factory-like effi­ciency to generate the data we did on this scale," says Jones. "For this project alone, we processed more than a quarter-million micro­scopes slides. That is an enormous data management challenge."
It is also the kind of project that, due to its broad nature, requires a specialized and dedicated team to pull off.
"This is not the kind of work that individual research labs should be doing," says Anderson, who is also a member of the institute's scientific advisory board. "What [researchers] should be doing is using their creativity to build on the information in the database to discover new biological principles and to find new cures for disease."
With its first major project com­plete, the institute now turns its attention to three specific areas, Jones says. First, it will continue to mine the information it has at hand and will create new tools for its use. Second, it will look to con­duct collaborative science with outside researchers to apply the information to disease-focused work.
"We have already engaged in early collaboration in areas like ALS, brain cancer and autism, just to name a few," Jones notes.
Finally—and perhaps most importantly—the institute is now moving it focus to the neocortex, a region that Jones notes "is argu­ably what makes us human" and an area that comprises about 80 percent of the human brain.

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