Monday, January 15, 2007

Mouse Mind Mega Map

In Richard Feynman's hilarious memoirs Surely You're Joking Mr. Feynman, he describes one incident where he confused a librarian by asking for 'a map of a cat'. The librarian ultimately realized that Feynman was looking for an anatomical chart.

Nowadays, it is common to have all sorts of maps of bodies -- genome maps, neural maps, cell fate maps, etc. On the flip side, one might fear that widespread adoption of talking GPS units will dull literacy for actual geographic maps. Progress!

Last week's Nature describes an audacious map of gene expression in the mouse brain -- 20K messages mapped by in situ hybridization. The work was largely funded by a foundation endowed by Microsoft founder Paul Allen, which might make one feel a little less guilty for tithing to Redmond -- Microsoft does much to earn enmity, but between this work & what the Gates Foundation is doing for diseases prevalent in Third World countries, it seems necessary to temper that ire.

The informatics required for this are extremely impressive. An inbred mouse strain was used for all the samples to reduce mouse-to-mouse variability, but what remained was solved by performing a three dimensional mouse brain alignment of all the samples (ClustalW is cool, but can it do that! :-)

The supplemental methods make clear the industrial scale of the project (boldface mine)
The production laboratory was built with specifications that allowed the ABA project a full capacity production of approximately 1,000 slides/4000 brain sections daily. The facility has strict environmental controls on air humidity and temperature as well as an RNAse-free water system capable of delivering the 300 liters of water necessary to run five robotic in situ hybridization platforms daily.
The News & Views item puts the final tally at over 1 million sections from 6000 brains.

Of course, like most genomics projects this isn't the be-all, end-all but rather an enormous database of hypotheses. For scientists interested in human brain diseases, clearly a first cut will be to verify whether genes showing interesting expression patterns in mouse show the same pattern in human. Undoubtedly there will also be many splice variants, alternative 3' & 5' ends, etc to characterize as well. But what a grand sandbox to explore!

Interestingly, the article itself seems to be freely accessible along with the Supplementary Material, but you'll need a subscription (or purchase access) to read the accompanying News & Views item on the paper. There is also a permanent database at http://www.brain-map.org

1 comment:

The Petri Dish said...

These types of studies are becoming more and more common and more and more powerful. The field of inbred strain genomics is rapidly expanding. Hopefully, with more work like this, complex trait analysis will be much less complex.