A high-resolution anatomical atlas of the transcriptome in the mouse embryo.

Ascertaining when and where genes are expressed is of crucial importance to understanding or predicting the physiological role of genes and proteins and how they interact to form the complex networks that underlie organ development and function. It is, therefore, crucial to determine on a genome-wide level, the spatio-temporal gene expression profiles at cellular resolution. This information is provided by colorimetric RNA in situ hybridization that can elucidate expression of genes in their native context and does so at cellular resolution. We generated what is to our knowledge the first genome-wide transcriptome atlas by RNA in situ hybridization of an entire mammalian organism, the developing mouse at embryonic day 14.5. This digital transcriptome atlas, the Eurexpress atlas (http://www.eurexpress.org), consists of a searchable database of annotated images that can be interactively viewed. We generated anatomy-based expression profiles for over 18,000 coding genes and over 400 microRNAs. We identified 1,002 tissue-specific genes that are a source of novel tissue-specific markers for 37 different anatomical structures. The quality and the resolution of the data revealed novel molecular domains for several developing structures, such as the telencephalon, a novel organization for the hypothalamus, and insight on the Wnt network involved in renal epithelial differentiation during kidney development. The digital transcriptome atlas is a powerful resource to determine co-expression of genes, to identify cell populations and lineages, and to identify functional associations between genes relevant to development and disease.

The Virtual Fly Brain browser and query interface.

MOTIVATION: Sources of neuroscience data in Drosophila are diverse and disparate making integrated search and retrieval difficult. A major obstacle to this is the lack of a comprehensive and logically structured anatomical framework and an intuitive interface. RESULTS: We present an online resource that provides a convenient way to study and query fly brain anatomy, expression and genetic data. We extended the newly developed BrainName nomenclature for the adult fly brain into a logically structured ontology that relates a comprehensive set of published neuron classes to the brain regions they innervate. The Virtual Fly Brain interface allows users to explore the structure of the Drosophila brain by browsing 3D images of a brain with subregions displayed as coloured overlays. An integrated query mechanism allows complex searches of underlying anatomy, cells, expression and other data from community databases. AVAILABILITY: Virtual Fly Brain is freely available online at www.virtualflybrain.org CONTACT: jda@inf.ed.ac.uk.

Web tools for large-scale 3D biological images and atlases.

BACKGROUND: Large-scale volumetric biomedical image data of three or more dimensions are a significant challenge for distributed browsing and visualisation. Many images now exceed 10GB which for most users is too large to handle in terms of computer RAM and network bandwidth. This is aggravated when users need to access tens or hundreds of such images from an archive. Here we solve the problem for 2D section views through archive data delivering compressed tiled images enabling users to browse through very-large volume data in the context of a standard web-browser. The system provides an interactive visualisation for grey-level and colour 3D images including multiple image layers and spatial-data overlay. RESULTS: The standard Internet Imaging Protocol (IIP) has been extended to enable arbitrary 2D sectioning of 3D data as well a multi-layered images and indexed overlays. The extended protocol is termed IIP3D and we have implemented a matching server to deliver the protocol and a series of Ajax/Javascript client codes that will run in an Internet browser. We have tested the server software on a low-cost linux-based server for image volumes up to 135GB and 64 simultaneous users. The section views are delivered with response times independent of scale and orientation. The exemplar client provided multi-layer image views with user-controlled colour-filtering and overlays. CONCLUSIONS: Interactive browsing of arbitrary sections through large biomedical-image volumes is made possible by use of an extended internet protocol and efficient server-based image tiling. The tools open the possibility of enabling fast access to large image archives without the requirement of whole image download and client computers with very large memory configurations. The system was demonstrated using a range of medical and biomedical image data extending up to 135GB for a single image volume.