Gene expression mapped across mouse brain

Researchers at the Allen Institute for Brain Science in Seattle have compiled a database of gene expression across the entire mouse brain, according to a report in Nature online this week. The open-access database, called the Allen Brain Atlas, contains searchable data and images from automated, high-throughput in situ hybridizations for nearly all of the mouse genome.

"It's very valuable information for people working on specific genes to be able to know where in the brain those genes are expressed," said Sacha Nelson of Brandeis University in Waltham, Mass., who was not involved in the project. "To be able to do that for essentially any gene is an important accomplishment."

Led by Ed Lein and Michael Hawrylycz at the Allen Institute, more than 100 researchers from several institutions collaborated to amass in situ data at cellular resolution for more than 20,000 mouse genes. The researchers analyzed mice from a single inbred strain. Automated signal detection and high-throughput techniques allowed the data to be collected in "a very aggressive three-year project," said Allan Jones, lead author of the report.

Previous research has analyzed gene expression in the mammalian brain, but at different resolutions than the Allen Brain Atlas, according to Carrolee Barlow of Brain Cells, Inc. in San Diego, who was not involved in the work. Projects using DNA microarrays and serial analysis of gene expression (SAGE) have provided highly quantitative gene expression data that lack cellular resolution. On the other hand, the GENSAT Project at Rockefeller University in New York has examined gene expression at the single-cell level, but only for a few thousand genes. The resolution of the Allen Brain Atlas falls somewhere in between, Barlow said.

The atlas researchers used the data to analyze overall gene expression in the brain, finding that about 80% of mouse genes are expressed somewhere in the adult brain. This is a higher percentage than expected, said Charles Stiles of Harvard University, who was not involved in the project. According to Jones, previous work had estimated that around 60% of the genome is expressed in the brain. The in situ data reveal that most genes are expressed in a small percentage of cells, which array-based techniques would likely fail to detect, Stiles said.

The data also reveal a great deal of cellular heterogeneity in the brain, Jones said. Based on differences in gene expression, brain cell types can be divided into many subtypes, which are presumably functionally different as well. "That's pretty surprising to me," Jones told The Scientist.

The scientists tested the atlas's detection of recognized cell markers and found that it identified essentially all well-established markers of brain cell types. It also revealed many previously unrecognized markers of different cell types. The atlas detected many but not all recognized markers of 12 major brain regions; it missed several genes known to be highly specific to certain regions.

Methods exist to ensure that the database doesn't miss these genes, Nelson told The Scientist, "but that would require individually tweaking every experiment in a way that they specifically wanted to avoid. They wanted to standardize things as much as possible."

According to Barlow, "you really have to take this as a guide" that needs to be verified by experimentation.

Researchers have been using the online atlas to guide experiments and corroborate evidence since the project's first data release in December 2004, which contained data on 2,000 genes, Jones said. Some scientists also use the atlas for data mining in a brain region of interest, Jones said. "They want very unique markers, and they just simply march through, gene by gene, looking for things that are highly enriched in this area." They then follow up by creating a transgenic animal or conducting other experiments, he said.

"A lot of people have been using it," Stiles told The Scientist. "The images are spectacular and the site is very user-friendly."

Melissa Lee Phillips
mphillips@the-scientist.com


Links within this article:

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http://www.the-scientist.com/article/display/15141

J. McCann, "Neuroscientists Benefit from Database Initiatives," The Scientist, January 8, 2001.
http://www.the-scientist.com/article/display/12211

E.S. Lein et al., "Genome-wide atlas of gene expression in the adult mouse brain," Nature, published online December 6, 2006.
http://www.nature.com/nature

Allen Brain Atlas
http://www.brain-map.org

Sacha Nelson
http://pyramid.bio.brandeis.edu/

Ed Lein
http://www.alleninstitute.org/content/ed_lein.htm

Michael Hawrylycz
http://www.alleninstitute.org/content/michael_hawrylycz.htm

C.Q. Choi, "Scientists welcome billionaire's brain project," The Scientist, September 22, 2003.
http://www.the-scientist.com/article/display/21608/

Allan Jones
http://alleninstitute.org/content/allan_jones.htm

Carrolee Barlow
http://www.braincellsinc.com/barlow.htm

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http://www.the-scientist.com/pubmed/16002470

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http://www.the-scientist.com/pubmed/16352711

S. Gong et al., "A gene expression atlas of the central nervous system based on bacterial artificial chromosomes," Nature, October 30, 2003.
http://www.the-scientist.com/pubmed/14586460

Charles Stiles
http://www.hms.harvard.edu/dms/bbs/fac/stiles.html

R. Sandberg et al., "Regional and strain-specific gene expression mapping in the adult mouse brain," PNAS, September 26, 2000.
http://www.the-scientist.com/pubmed/11005875