eMouseAtlas informatics: embryo atlas and gene expression database - PubMed (original) (raw)

eMouseAtlas informatics: embryo atlas and gene expression database

Chris Armit et al. Mamm Genome. 2015 Oct.

Abstract

A significant proportion of developmental biology data is presented in the form of images at morphologically diverse stages of development. The curation of these datasets presents different challenges to that of sequence/text-based data. Towards this end, the eMouseAtlas project created a digital atlas of mouse embryo development as a means of understanding developmental anatomy and exploring the relationship between genes and development in a spatial context. Using the morphological staging system pioneered by Karl Theiler, the project has generated 3D models of post-implantation mouse development and used them as a spatial framework for the delineation of anatomical components and for archiving in situ gene expression data in the EMAGE database. This has allowed us to develop a unique online resource for mouse developmental biology. We describe here the underlying structure of the resource, as well as some of the tools that have been developed to allow users to mine the curated image data. These tools include our IIP3D/X3DOM viewer that allows 3D visualisation of anatomy and/or gene expression in the context of a web browser, and the eHistology resource that extends this functionality to allow visualisation of high-resolution cellular level images of histology sections. Furthermore, we review some of the informatics aspects of eMouseAtlas to provide a deeper insight into the use of the atlas and gene expression database.

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Figures

Fig. 1

Fig. 1

The three main components of eMouseAtlas can be accessed from the eMouseAtlas portal page (a). These are EMA (mouse anatomy atlas) (b), eHistology (online access to histology images and annotations) (c), and EMAGE (gene expression database) (d)

Fig. 2

Fig. 2

This 3D reconstruction of an eMouseAtlas TS17 embryo is visualised using an IIP3D web tool. The X3DOM interactive 3D surface display (inset) allows the user to easily navigate through the 3D space of the models with the green disc delivering feedback on the plane of section. The IIP3D viewer (centre panel) allows users to interactively view anatomy domains. Manipulations that can be performed on the displayed image include pan-and-zoom; translating the viewing plane (i.e., distance); and rotating the viewing plane in three dimensions (pitch, yaw, roll). There is the additional option to select layers (right panel), and this allows visualisation of delineated anatomical domains

Fig. 3

Fig. 3

The eHistology interface (a) consists of a main panel showing the chosen section with the list of annotations relating to the selected plate and image shown on the right hand side. The user is able to choose to only see closest marker pins to the cursor, or to “show all” pins on the current view. Left clicking on any marker pin will open a pop-up window (b) containing further information and links relating to the structure defined by that marker pin. There are navigation and magnification controls on the left hand side of the main panel. These allow the user to navigate between sections as well as to zoom in on any region of the section to cellular resolution (c)

Fig. 4

Fig. 4

EMAGE “embryo space” query tool (a) allows users to “paint” a query region on a model (inset). This painted region is used to query the database for mapped patterns that overlap with the query region. These results are ordered by similarity to the query region. The “find similar” tool (b) takes a chosen entry (inset) and uses the mapped pattern for that entry to query for syn-expression in other entries. The results are ranked by similarity to the query domain, in this case the mapped pattern for the chosen gene (Foxc2). The “spatial clustering” tool (c) allows users to select a node in a tree view of spatially similar patterns (left). This node can be viewed as a spatial heatmap of expression (middle). There is the additional option to view this heatmap alongside the composite of original images that were used to generate a particular node

Fig. 5

Fig. 5

Colour map showing occupancy of spatially mapped Wnt gene expression patterns. An interactive IIP3D viewer is used to deliver a mid-sagittal section through a TS17 model. Spatially mapped Wnt gene expression patterns are visualised as occupancy maps with the number of Wnt patterns per voxel displayed as distinct colours. In this visualisation, the domain of zero occupancy (i.e., no Wnt gene expression) is shown in blue, whereas single occupancy (only one Wnt gene) is shown in green, dual occupancy (two Wnt genes) is shown in yellow, and occupancy scores of three or more patterns (three or more Wnt genes) are shown in red. This reveals region of high co-expression (potential signalling centres) and low co-expression within a given gene family. Users are able to interactively explore the occupancy map in more detail using mouseover, which delivers a list of mapped gene expression domains and anatomy domains per voxel

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