Abstract
High-throughput phenotyping is a cornerstone of numerous functional genomics projects. In recent years, imaging screens have become increasingly important in understanding gene–phenotype relationships in studies of cells, tissues and whole organisms. Three-dimensional (3D) imaging has risen to prominence in the field of developmental biology for its ability to capture whole embryo morphology and gene expression, as exemplified by the International Mouse Phenotyping Consortium (IMPC). Large volumes of image data are being acquired by multiple institutions around the world that encompass a range of modalities, proprietary software and metadata. To facilitate robust downstream analysis, images and metadata must be standardized to account for these differences. As an open scientific enterprise, making the data readily accessible is essential so that members of biomedical and clinical research communities can study the images for themselves without the need for highly specialized software or technical expertise. In this article, we present a platform of software tools that facilitate the upload, analysis and dissemination of 3D images for the IMPC. Over 750 reconstructions from 80 embryonic lethal and subviable lines have been captured to date, all of which are openly accessible at mousephenotype.org. Although designed for the IMPC, all software is available under an open-source licence for others to use and develop further. Ongoing developments aim to increase throughput and improve the analysis and dissemination of image data. Furthermore, we aim to ensure that images are searchable so that users can locate relevant images associated with genes, phenotypes or human diseases of interest.
Highlights
High-throughput phenotyping is instrumental to the goals of the International Mouse Phenotyping Consortium (IMPC), a global endeavour to systematically produce and characterize a knockout mouse for every gene in the mouse genome [1]
Three-dimensional (3D) imaging has risen to prominence in the field of developmental biology for its ability to capture whole embryo morphology and gene expression, as exemplified by the International Mouse Phenotyping Consortium (IMPC)
We present a platform of software tools that facilitate the upload, analysis and dissemination of 3D images for the IMPC
Summary
High-throughput phenotyping is instrumental to the goals of the International Mouse Phenotyping Consortium (IMPC), a global endeavour to systematically produce and characterize a knockout mouse for every gene in the mouse genome [1]. Users can search for genes or anatomical structures of interest and view gene expression profiles as high-resolution histological sections or pre-rendered 3D volumes Each of these portals provides new data in the form of releases, and so may remain relatively static for prolonged periods. The high-throughput nature of the IMPC requires a platform that can retrieve and disseminate images more frequently as and when they become available, while ensuring that data submitted by different institutions conform to the necessary standards for visualization and analysis. We present a suite of software tools for the capture, processing, analysis, visualization and dissemination of 3D images These tools have been used extensively in support of recent work on the discovery of novel developmental phenotypes, in which high-throughput 3D imaging has played an integral role [19]. Primarily developed for the IMPC, all of the software is made available under an open-source licence to encourage wider adoption as standalone tools or as part of other 3D imaging pipelines
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