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API: Allen Human Brain Atlas Resources

Human Brain Microarray Survey
-----------------------------

The [Allen Human Brain Atlas](http://human.brain-map.org) is an online multimodal atlas of the human brain that
integrates anatomic and microarray-based gene expression information. Microarray sampling sites
(~400-1000 sites per brain) were identified by expert anatomists using cytoarchitectural information from multiple
histological stains. Sampling site delineations in the high resolution histological images were subsequently mapped
into each individual's MR image space to provide 3-D anatomical context. All brains are also registered to MNI space to
enable cross-individual comparisons.

[Online](http://human.brain-map.org) and [desktop interactive tools](http://human.brain-map.org/explorer.html) were
developed to navigate and visualize the data. All expression values and images are available through the Allen
Institute API.

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### Microarray Data

RNA isolated from each sample area was hybridized to a custom Agilent 8x60k microarray chip to measure gene expression
over the transcriptome. All least two different probes were available for 93% of genes. Probes were located on different
exons as much as possible when multiple probes were available for a gene. For 60 genes, a set of tiling probes were
probes was designed.

Each sampling site is associated to a

Unknown macro: {Structure}

by expert anatomist using cytoarchitectural information from multiple
histological stains. Structures are arranged in a [hierarchical organization](/api/v2/structure_graph_download/10.json).
Each structure has one parent and denotes a "part-of" relationship. Structures are assigned a color to visually
emphasize their hierarchical positions in the brain.

Gene expression data for samples passing quality control were normalized first within a single brain using a cross-batch
normalization algorithm called [ComBat](http://www.bu.edu/jlab/wp-assets/ComBat/Abstract.html). In order to allow
comparison across two or more brains, a cross-brain normalization was performed by aligning the mean 75th percentile
expression values of all internal reference control samples of each brain to that of the first brain (H0351.2001). See
the [whitepaper](http://help.brain-map.org/display/humanbrain/Documentation) for more details on microarray data
generation and processing.

Normalized microarray expression values can be downloaded in a simple
[numerical matrix format](http://human.brain-map.org/static/download) from the web application or through the
[Microarray Data Service](#Accessing_the_Microarray_Data_Service).

All experimental data from this study is associated with the
[Human Brain Microarray Product](/api/v2/data/Product/query.xml?id=2). All probe and sampling site information can be
accessed through the API using [RMA](#RESTful_Model_Access_RMA).

*Example queries:*

* [All donors in the Product](/api/v2/data/Donor/query.xml?include=age&criteria=products[id$eq2])
* [All sampling sites in the Product](/api/v2/data/query.xml?criteria=model::Sample,rma::criteria,microarray_data_set(products[abbreviation$eq'HumanMA']),rma::include,structure,microarray_slides(well_known_files))
* [All microarray probes in the Product](/api/v2/data/Probe/query.xml?criteria=[probe_type$eq%27DNA%27],products[abbreviation$eq%27HumanMA%27]&include=gene,predicted_sequence)
* [All microarray probes associated with gene prodynorhphin (PDYN)](/api/v2/data/Probe/query.xml?criteria=[probe_type$eq'DNA'],products[abbreviation$eq'HumanMA']&include=gene[acronym$eq'PDYN'],predicted_sequence)
* [All samples associated with donor "H0351.2001" and the dentate gyrus](/api/v2/data/query.xml?criteria=model::Sample,rma::criteria,microarray_data_set(products[abbreviation$eq'HumanMA'],specimen(donor[name$eq'H0351.2001'])),structure[acronym$eq'DG'],rma::include,structure,microarray_slides(well_known_files))
* [Download an "raw" Aglient output file for one sample using the download-link](/api/v2/well_known_file_download/3436)(warning: large file)

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#### Expression Values

Normalized expression values can be obtained by specifying a list of probes using the [RMA connected services and pipes](#Connected_Services_and_Pipes).

*Example:* Download expression values for all probes associated with PDYN

* [*Pipe:* Find all probes associated with gene PDYN](/api/v2/data/query.xml?criteria=model::Probe,rma::criteria,[probe_type$eq'DNA'],products[abbreviation$eq'HumanMA'],gene[acronym$eq'PDYN'],rma::options[only$eq'probes.id'])
* [Connect pipe to *service::human_microarray_expression* to download expression values](/api/v2/data/query.json?criteria=model::Probe,rma::criteria,[probe_type$eq'DNA'],products[abbreviation$eq'HumanMA'],gene[acronym$eq'PDYN'],rma::options[only$eq'probes.id'],pipe::list[xprobes$eq'id'],service::human_microarray_expression[probes$in$xprobes])

The output of the service is two top level ordered arrays "samples" and "probes". For example:

    "samples":[
           {"donor":

Unknown macro: {"id"}

,
            "sample":

Unknown macro: {"well"}

,
            "structure":

Unknown macro: {"id"}

,
            "top_level_structure":{"id":4009,"name":"Frontal Lobe","abbreviation":"FL","color":"E8CD59"}},
           {"donor":

Unknown macro: {"id"}

,
            "sample":

Unknown macro: {"well"}

,
            "structure":

Unknown macro: {"id"}

,
            "top_level_structure":{"id":4009,"name":"Frontal Lobe","abbreviation":"FL","color":"E8CD59"}},
           ...
           ]
    "probes":[
       

Unknown macro: {"id"}

,
       

Unknown macro: {"id"}

,
        ...
        ]

Each *sample* contains information about:

* the

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(id, name, age),
* the

Unknown macro: {Sample}

(well id and (x,y,z) coordinate in the MR volume in millimeters),
* the associated

(id, name, acronym and color), and
* the associated top (coarse) level Structure (id, name, acronym and color).

Each *probe* contains information about:

* the

Unknown macro: {Probe}

(id, name), and
* the

Unknown macro: {Gene}

(id, acronym, name, entrez-id), along with
* a vector of normalized expression values in the same order as the "samples" array.

Usage of this service is demonstrated in the [scatter plot](/examples/scatter/index.html) and
[SPM](/examples/spm/index.html) example applications. Also see [example code](/examples/brodmann/index.html) on how to
transform each microarray sample to MNI space.

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