Allen Brain Atlas: an integrated spatio-temporal portal for exploring the central nervous system

Abstract

The Allen Brain Atlas (http://www.brain-map.org) provides a unique online public resource integrating extensive gene expression data, connectivity data and neuroanatomical information with powerful search and viewing tools for the adult and developing brain in mouse, human and non-human primate. Here, we review the resources available at the Allen Brain Atlas, describing each product and data type [such as in situ hybridization (ISH) and supporting histology, microarray, RNA sequencing, reference atlases, projection mapping and magnetic resonance imaging]. In addition, standardized and unique features in the web applications are described that enable users to search and mine the various data sets. Features include both simple and sophisticated methods for gene searches, colorimetric and fluorescent ISH image viewers, graphical displays of ISH, microarray and RNA sequencing data, Brain Explorer software for 3D navigation of anatomy and gene expression, and an interactive reference atlas viewer. In addition, cross data set searches enable users to query multiple Allen Brain Atlas data sets simultaneously. All of the Allen Brain Atlas resources can be accessed through the Allen Brain Atlas data portal.

Figure 1.

Transcriptome RNA sequencing heat maps. The transcriptome heat map is a visualization of the expression values for the returned gene of interest (top panel). In this example, the Find Correlates search returns (search by example) are shown for DCX (doublecortin), which has high expression during prenatal development. The heat map data is presented as a matrix with brain structure (by developmental stage) on the x-axis and genes on the y-axis. Brain structures are organized in ontological order. Clicking on the toggle button will change the initial sorting parameter from structure to developmental stage. In this example, data is sorted by structure, and then by the youngest to oldest developmental stage within each structure. Each column of the heat map represents a tissue sample. The colors of the heat map are expression values, transformed to a log₂ scale. The color scale ranges from dark blue, representing low expression, and passes through cyan, yellow and orange and finally to dark red, representing high expression. The lower panel presents the exon heat map view of the RNA sequencing data for DCX. Each row of the heat map in the RNA sequencing data represents an exon. Exons in the RNA sequencing data are labeled by the chromosome start position and exon length. Positioning the mouse over an exon highlights the corresponding exon in the schematic composite gene model.

Figure 2.

Interface of Brain Explorer software for viewing brain anatomy and gene expression data in 3D. The main window of the Brain Explorer application displays Rab37 expression in a coronal slice from the adult mouse brain, in which gene expression is indicated by colored spheres. The location of the thalamic structure ventral anterior-lateral complex is shown in muted pink. The structural ontology panel on the right-hand side shows the color-coded hierarchy, which can be switched between hierarchical and alphabetical mode. Bookmarks portray saved default and custom views. At the bottom right-hand side of the window is the list of genes shown in the 3D view.

Figure 3.

Reference Atlas integration with ISH and connectivity data. The top four images show gene expression data from ISH experiments with LOC433228, Adamts19 and Rab37 along with the P56 mouse reference atlas. All three have strong expression in a subset of thalamic nuclei (red), such as the dorsal part of the lateral geniculate complex (LGd), ventral posteromedial nucleus of the thalamus (VPM) and ventral posterolateral nucleus of the thalamus (VPL). The lower four images show views of the projections (connectivity data) from dorsal auditory area (AUDd), primary motor area (MOp) and SSB-bfd (primary somatosensory area, barrel field), along with the P56 mouse reference atlas. These three neuroanatomical regions have axonal projections to the thalamus. The side-by-side viewing of the reference atlas with various data modalities enables one to glean where the gene is expressed and what brain regions are interconnected, respectively.

Figure 4.

Interactive Reference Atlas Viewer. The top left hand panel portrays an annotated coronal reference atlas plate from the P56 mouse (Allen Mouse Brain Atlas) in the High Resolution Image Viewer. At the top of the image is the hippocampus (green), and in the middle of the image is the thalamus (red) and its corresponding subdivisions (subnuclei). The top right hand panel presents the same annotated adult mouse reference atlas plate in the Interactive Reference Atlas Viewer. This viewer is divided into two windows, a collapsible hierarchical tree of brain structures on the left and annotated images of the Nissl-stained reference sections on the right that displays the images in a Zoom and Pan Image Viewer. Polygons scale and move with the image as one zooms in and out or moves the image in any direction. Moving the computer cursor over the image highlights individual structures; the structure name and acronym are displayed at the top of the window. Clicking on a structure also highlights the structure in the structure hierarchy. The lower panel shows coronal annotated reference atlas plates from the BrainSpan Atlas of the Developing Human Brain from a 15 pcw (post conception weeks), 21 pcw and 34 year reference atlas. The thalamus and its corresponding subregions (subnuclei) are purple in the human atlases. With the reference atlas viewers, one can examine neuroanatomy across time within an individual species (mouse or human), as well as across species (mouse versus human).