Human brain atlas project
From Biohack
2008-03-15: Gene expression in the Human Cortex project. The methodology here seems to be the same as the mouse brain atlas. Slices of neural tissue are bathed in mRNA probes, this is basically a microarray with scanned visuals of the tissue itself (kind of like the connectomics project from Harvard).
The email
On Saturday 15 March 2008, Bryan Bishop <kanzure@gmail.com> wrote:
> ---------- Forwarded Message ----------
>
> Subject: [tt] kurzweill: newscientist: human brain atlas project
> funded Date: Saturday 15 March 2008
> From: Alejandro Dubrovsky <alito@organicrobot.com>
> To: transhumantech
>
> (
> 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.
- 2008-03-15: I would like to note that the Blue Gene simulation project also was doing individual cell information, down to the ion channels in the plasma membrane (I was reading an article about this earlier today, forwarded it to hplusroadmap and Puckett), which was what Endos127 was talking about last night re: molecular dynamics and computational chemistry over at Florida State University (Wei Yang, I believe), and the CHARMM software package ([1] maybe). -- Kanzure 04:56, 15 March 2008 (CDT)
>
> 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 mRNA 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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