[Hplusroadmap] Fwd: [tt] kurzweill: newscientist: human brain atlas project funded

[Bryan Bishop]

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Subject: [tt] kurzweill: newscientist: human brain atlas project funded
Date: Saturday 15 March 2008
From: Alejandro Dubrovsky <alito at organicrobot.com>
To: transhumantech <tt at postbiota.org>

(
http://www.newscientist.com/article/dn13458-brain-map-project-set-to-revolutionise-neuroscience.html
Also FAQ below (not in there: expected differences in gene expression
between old, dead and frozen compared to warm, young and spritely brain
tissue)
http://humancortex.alleninstitute.org/has/common/content/FAQ.pdf
)

Brain map project set to revolutionise neuroscience

 * 12:07 13 March 2008
 * NewScientist.com news service
 * Peter Aldhous

Take the most complex organ in the human body, superimpose the legacy of
biology’s biggest research project, and what have you got? An
unprecedented brain map that is set to transform studies of neuroscience
and brain disease.

The Allen Institute for Brain Science in Seattle, Washington, US, is
today launching a four-year, $55-million effort to build a
three-dimensional map documenting the levels of activity of some 20,000
different genes across the human brain.

“The Human Genome Project was the ‘what’, and our project is the
‘where’,” says Allan Jones, the institute’s chief scientific officer.

Established in 2003 with a $100-million gift from Microsoft co-founder
Paul Allen, the Allen institute has already created a similar atlas of
the mouse brain, unveiled in December 2006.

By revealing patterns of gene activity, the mouse atlas has allowed
neuroscientists to identify functionally important regions that were
invisible simply by looking at the brain’s anatomy.
Evolution insights

“That’s why the brain is such a unique structure,” says Greg Foltz, a
neurosurgeon at the Swedish Neuroscience Institute, also in Seattle.
“Its function is very much embedded in its anatomy.”

Foltz’s team has also used the mouse atlas to help home in on two genes,
known as BEX1 and BEX2, which seem to be silenced in a form of brain
cancer called glioma. An atlas of the human brain should be an even more
powerful tool in identifying what goes wrong at the gene level in cancer
and other diseases, he says.

For instance, some neuroscientists suspect that autism may be linked to
abnormalities in a paired structure called the amygdala, involved in
processing emotional information. This can be tested by comparing
patterns of gene activity in autistic people with that in the atlas,
which will be drawn up by studying the brains of recently deceased
healthy people.

Comparisons between the mouse and human brain atlases should also yield
insights into the evolution of our advanced cognitive abilities,
suggests David Anderson, a neuroscientist at the California Institute of
Technology in Pasadena, and one of the Allen institute’s scientific
advisers. “Are there fundamental differences in the organisation of the
brain?” he asks.
Huge task

The sheer size of the human brain will make the new project a much
bigger challenge.

The mouse atlas was produced using a method called “in situ
hybridisation”, in which thin slices of brain tissue are bathed in a
solution containing molecular probes that bind to messenger RNA
sequences produced by each gene. This gives a very detailed map of gene
activity, down to the level of individual cells.

Trying to repeat this effort for all 20,000 genes across an organ about
2000 times larger than the mouse brain is impractical, for now. So Allen
institute scientists will instead divide the human brain into between
500 and 2000 anatomical regions, and study gene activity in each by
washing extracts from tissues in these regions across “gene chips” that
can record which messenger RNA is present.

Once results from this initial phase of the project are in, which will
take about two years, the institute’s scientists will perform in situ
hybridisation across the whole brain for up to 500 genes with the most
interesting patterns of activity.

As well as launching the human brain atlas, the Allen institute is
starting two further projects. The first, costing around $15 million
over the next two years, will look at the activity of around 4000 mouse
genes at different stages in embryological and juvenile development.

A second project, taking about a year to complete at a cost of $2
million, will make an atlas of gene activity in the mouse spinal cord.

The Human Brain - With one hundred billion nerve cells, the complexity
is mind-boggling. Learn more in our cutting edge special report.

Genetics - Keep up with the pace in our continually updated special
report.

---

FAQ: Gene Expression in the Human Cortex

General

What is the goal of this project?


The goal of this project is to provide the scientific community with a
free, open resource for accessing human cortical brain gene expression
information with cellular resolution.

What features are available in this application?

Users will find a searchable dataset of ISH images organized by gene,
cortical region, donor and tissue characteristics. A toggle feature
allows viewing of raw ISH images and pseudo-color gene expression
masks, and images can be viewed as sets or individually with zoom and
pan features. Nearest Nissl data are available for each image or image
set. An alphabetically organized gene list is available for browsing.
Users can click the “?” to access Help for all features on each
application page.

Project Methods

Where can I get in-depth methods information for this project?

Please visit the documentations page
(http://humancortex.alleninstitute.org/has/human/docs.html) to access
a technical white paper describing methods and references for probe
design, tissue and RNA quality characterization, ISH processes, image
acquisition, data processing and quality control.  Acknowledgements
and answers to FAQ may also be found on the documentations page.

How are cases selected for gene expression characterization?

Postmortem human brain samples from subjects with no evidence of
micro- or macro-neuropathology and no known history of
neuropsychiatric disease or drug use are selected to provide baseline
characterization of gene expression.

How are tissue samples obtained?

Tissue samples are obtained from established tissue repositories that
provide well-characterized frozen postmortem tissue
samples. Applicable regulatory guidelines governing human subjects
research are adhered to, and at no time is any information that could
identify a subject (e.g. first or last name) requested or received by
the Allen Institute.

Will this be a genome-wide dataset?

Approximately 1,000 genes will be characterized in multiple
individuals during the course of this project and several data
releases are planned as data are generated. The genes cover a range of
families, including ion channels, GPCRs, transporters, synaptic
proteins, cortical and cell type markers, disease related genes and
genes of interest in the comparative genomics field.

What is a RIN number?

RNA integrity number, or RIN, is a metric commonly used to indicate
quality of RNA extracted from tissue samples and is assumed to reflect
the quality of RNA in tissue sections used for ISH. RINs range from 1
to 10, with 10 indicating intact RNA. RIN may vary due to sample
specific characteristics and may be influenced by assay parameters for
RNA extraction and RIN measurement. Additional information may be
accessed via the documentation page.
http://humancortex.alleninstitute.org/has/human/docs.html.

What is PMI?

PMI is an acronym for ‘postmortem interval’, the duration of time
(expressed in hours) between actual or estimated time of death and
time that tissue samples are frozen. PMI is often reported in the
literature as one indication of tissue quality. It has also been
reported that postmortem interval has at most a modest effect on RNA
quality. Additional information may be accessed via the documentation
page.  http://humancortex.alleninstitute.org/has/human/docs.html.

What does pH information tell me?

Brain tissue pH may be an indicator of RNA integrity by virtue of its
relationship to agonal state. Tissue samples used in this dataset have
a cerebellar pH of 6 or higher. Additional information may be accessed
via the documentation
page. http://humancortex.alleninstitute.org/has/human/docs.html.

Are any criteria in place for tissue samples?

Standard criteria that reflect the range of criteria in the literature
are in place. PMI, pH, and RIN are presented to allow users to assess
data according to user-specific needs. Additional information may be
accessed via the documentation
page. http://humancortex.alleninstitute.org/has/human/docs.html.

What probes are used?

Digoxigenin-labeled riboprobes for target mRNA are made using cDNA
clones or pooled cDNA prepared from pooled total human brain RNA as
templates. All probes are designed with specific criteria to minimize
cross-hybridization with non-target mRNA but are pan-specific for
alternative splice variants.  Where applicable, probes are designed to
match corresponding Allen Brain Atlas mouse orthologs.  Additional
information may be accessed via the documentation page.
http://humancortex.alleninstitute.org/has/human/docs.html.

How are images generated?

ISH and Nissl slides are digitized using either the image capture
system (ICS) created by the Allen Institute or the ScanScope system
from Aperio Technologies, Inc. The ICS system creates images with the
desired resolution (~ 1 μm per pixel) by stitching individual tiles to
form a composite image of the entire section. The ScanScope system
currently being used creates images at the same 1 μm/pixel resolution
using line scanning technology that results in more consistent focus
and greater image acquisition speed.

Is there anything I can do to better visualize lightly stained tissue?

The addition of an acid wash step enhances data quality by greatly
reducing background and also produces lightly stained tissue,
particularly when gene expression is sparse. When viewing image sets,
a slider bar is available to adjust the darkness of both ISH and
pseudo-color images. Contrast and brightness settings are adjustable
in the single image viewer. Zooming to higher resolution on a specific
region on the image is also effective for better visualization of the
data.

Citation and Use

What is the appropriate way to cite this resource?

Details on appropriate citation of this resource are available in the
Allen Institute’s Citation Policy at
http://www.alleninstitute.org/citation_policy.htm.

What are your terms of use?

The Allen Institute provides this dataset as a free, open resource for
the scientific community. Users are encouraged to use this resource to
support, for example, research, teaching, grant applications,
publications and presentations, as per the Terms of Use, available at:
http://www.alleninstitute.org/terms_of_use.htm.

What is your privacy policy?

The privacy policy explaining the practices of the Allen Institute
regarding the collection, storage and disclosure of information
obtained through its websites is found at:
http://www.alleninstitute.org/privacy_policy.htm.



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Bryan Bishop
http://heybryan.org/