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Allen Brain Atlas API

The Allen Human Brain Atlas is a 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.

From the API, you can:

Download expression values
Query the correlative and differential search services
Download MRI images

Experimental Overview and Metadata

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 Structure by expert anatomist using cytoarchitectural information from multiple histological stains. Structures are arranged in a hierarchical organization. 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.

See the structure ontology page for more information.

Gene expression data for samples passing quality control are normalized to enable cross-comparison between batches and donors. See the whitepaper for more details on microarray data generation and processing.

Normalized microarray expression values can be downloaded in several ways:

From the web application Download page. Each zip file contains the normalized values for all probes and all samples for one donor )
From the "Download this data" link below the heatmap in the web application.
From the connected data service in the API

All experimental data from this study is associated with the "Human Brain Microarray" Product. All probe and sampling site information can be accessed through the API using RMA queries.

Example queries:

Downloading Expression Values

Normalized expression values can be obtained by specifying:

a list of probes
a list of donors (optional), and
a list of structures (optional)

See the connected service page for definitions of service::human_microarray_expression parameters.

Example:

Download expression values for donor "H0351.1015" in structure "locus ceruleus" for all probes associated with gene SLC6A.

Find Donor ID for "H0351.1015" (id = 15496)

http://api.brain-map.org/api/v2/data/query.xml?criteria=model::Donor,
rma::criteria,[name$eq'H0351.1015'],
rma::options[only$eq'donors.id']

Find Structure ID for "locus ceruleus" (id = 9148)

http://api.brain-map.org/api/v2/data/query.xml?criteria=model::Structure,
rma::criteria,[name$il'locus ceruleus'],ontology[name$eq'Human Brain Atlas'],
rma::options[only$eq'structures.id']

Find Probes associated with gene SLC6A (id = 1023146,1023147 )

http://api.brain-map.org/api/v2/data/query.xml?criteria=model::Probe,
rma::criteria,[probe_type$eq'DNA'],products[abbreviation$eq'HumanMA'],gene[acronym$eq'SLC6A2'],
rma::options[only$eq'probes.id']

Use Donor, Structure and Probe IDs as parameters to the connected service

http://api.brain-map.org/api/v2/data/query.json?criteria=
    service::human_microarray_expression[probes$eq1023146,1023147][donors$eq15496][structures$eq9148]

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

"probes":[{
    "id":1023146,
    "name":"A_23_P358345",
    "gene-id":6494,
    "gene-symbol":"SLC6A2",
    "gene-name":"solute carrier family 6 (neurotransmitter transporter, noradrenalin), member 2",
    "entrez-id":6530,"chromosome":"16","start-position":"n/a","end-position":"n/a",
    "expression_level":["13.2802","13.9603","13.9650"],
    "z-score":["9.3381","9.8663","9.8700"]},
    {
    "id":1023147,
    "name":"CUST_16472_PI416261804",
    "gene-id":6494,
    "gene-symbol":"SLC6A2",
    "gene-name":"solute carrier family 6 (neurotransmitter transporter, noradrenalin), member 2",
    "entrez-id":6530,"chromosome":"16","start-position":"n/a","end-position":"n/a",
    "expression_level":["8.1878","8.5644","8.2310"],
    "z-score":["9.3201","9.8326","9.3790"]}
    ],
"samples":[
    {"donor":{"id":15496,"name":"H0351.1015","age":"49 years","color":"C2C200"},
    "sample":
        {"well":148955246,"polygon":127107914,"mri":[95,121,126]},
        "structure":{"id":9149,"name":"locus ceruleus, Left","abbreviation":"LC","color":"00FFAA"},
        "top_level_structure":{"id":9135,"name":"Pontine Tegmentum","abbreviation":"PTg","color":"00FFAA"}},
    {"donor":{"id":15496,"name":"H0351.1015","age":"49 years","color":"C2C200"},
    "sample":
        {"well":148955204,"polygon":126786164,"mri":[97,151,131]},
        "structure":{"id":9149,"name":"locus ceruleus, Left","abbreviation":"LC","color":"00FFAA"},
        "top_level_structure":{"id":9135,"name":"Pontine Tegmentum","abbreviation":"PTg","color":"00FFAA"}},
    {"donor":{"id":15496,"name":"H0351.1015","age":"49 years","color":"C2C200"},
    "sample":
        {"well":156435966,"polygon":126789834,"mri":[96,159,134]},
        "structure":{"id":9149,"name":"locus ceruleus, Left","abbreviation":"LC","color":"00FFAA"},
        "top_level_structure":{"id":9135,"name":"Pontine Tegmentum","abbreviation":"PTg","color":"00FFAA"}}
    ]

Each probe contains information about:

the Probe(id, name), and
the Gene (id, acronym, name, entrez-id), along with
a vector of normalized expression values in the same order as the "samples" array.
a vector of z-score values in the same order as the "samples" array. Note: z-score is computed independently for each probe over all donors and samples.

Each sample contains information about:

the Donor (id, name, age),
the Sample (well id and (x,y,z) coordinate in the MR volume in millimeters),
the associated Structure (id, name, acronym and color), and
the associated top (coarse) level Structure (id, name, acronym and color).

Usage of this service is demonstrated in the scatter plot and SPM example applications. Also see example code on how to transform each microarray sample to MNI space.

Differential search

Differential search find probes that show the greatest difference between two sets (target and contrast) of user-defined structures. For each probe, a 2-sample t-test is performed followed by Benjamini and Hochberg false discovery rate correction. The null hypothesis is that the average expression level of samples in the contrast set of structures is less than the average expression level of samples in the target set of structures. Resulting p-values are sorted in ascending order. Search results can also be sorted by fold-change (log ratio of expression) in descending order.

The differential search function can be access through the Web application or using the API.

See the connected service page for definitions of service::human_microarray_differential parameters.

Example:
Differential search for genes with higher expression in thalamus than the cerebral cortex

Find Structure ID for "thalamus" (id = 4392)

http://api.brain-map.org/api/v2/data/query.xml?criteria=model::Structure,
rma::criteria,[name$il'thalamus'],ontology[name$eq'Human Brain Atlas'],
rma::options[only$eq'structures.id']

Find Structure ID for "cerebral cortex" (id = 4008)

http://api.brain-map.org/api/v2/data/query.xml?criteria=model::Structure,
rma::criteria,[name$il'cerebral cortex'],ontology[name$eq'Human Brain Atlas'],
rma::options[only$eq'structures.id']

Use Structure IDs as parameters to the connected service

http://api.brain-map.org/api/v2/data/query.xml?criteria=service::human_microarray_differential
    [structures1$eq4008][structures2$eq4392][sort_by$eq'fold-change']

Visualize the same search result in the Web application

Figure: Screenshot of top returns of a differential search for genes with higher expression in the thalamus than the cerebral cortex. Z-score heatmap shows enrichment (red) in the thalamus (structure color: light green) compare to other brain regions.

Usage of this service is demonstrated in the SPM example application.

Correlative search

Correlative search finds probes with similar expression profile to the selected seed probe over all samples within a user-specified structure. Pearson's correlation coefficient is computed for all probes and results ranked in descending order.

This correlative search function can be access through the Web application or using the API.

See the connected service page for definitions of service::human_microarray_correlation parameters.

Example:
Correlative search for probes with similar expression to PVALB probe CUST_11451_PI416261804 over the whole Brain

Find Probe ID for probe "CUST_11451_PI416261804" (id = 1052410)

http://api.brain-map.org/api/v2/data/query.xml?criteria=model::Probe,
rma::criteria,[name$eq'CUST_11451_PI416261804'],
rma::options[only$eq'probes.id']

Find Structure ID for "Brain" (id = 4005)

http://api.brain-map.org/api/v2/data/query.xml?criteria=model::Structure,
rma::criteria,[name$il'brain'],ontology[name$eq'Human Brain Atlas'],
rma::options[only$eq'structures.id']

Use Probe and Structure IDs as parameters to the connected service

http://api.brain-map.org/api/v2/data/query.xml?criteria=service::human_microarray_correlation
    [probes$eq1052410][structures$eq4005]

Visualize the same search result in the Web application

Figure: Screenshot of top returns of a correlative search for probes with similar expression to a PVALB probe with expression values displayed as a z-score heatmap.

Magnetic Resonance Imaging

T1-weighted MPRAGE scans were acquired the postmortem brains using 3T Siemens Trio MR scanners (TI=900ms, TR=1900ms, TE=3.03ms, 9 degree flip angle, 1mm isotropic voxels). Scans were performed in cranio for some brains and ex cranio for others. See the Microarray white paper for more specific scan sequence details for each brain.

Figure: T1 MR scan for donor 'H0351.2002'

The T1, T2 and DTI (if available) volumetric data can be downloaded from the Web application or via the API.

All T1 images were registered to MNI space. FreeSurfer's affine registration was used for the in cranio scans. For ex cranio brains, the T1 was first rigidly aligned using FSL (Jenkinson, et. al, 2002) and then non-rigidly aligned using ANTS (Avants, et. al., 2011). The 3-D affine transform from a location in the MR volume to MNI space is encapsulated in the Alignment3d model.

Examples queries:

See example code on how to transform each microarray sample to MNI space.

http://iwarehouse/doc/index.html

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