Public archiving and data integration in the era of multi-modal imaging

设想这样一个场景：一个人可以给整个生物体成像，然后逐步放大到器官、组织、细胞、分子，最后是原子的水平，每一步都能揭示更多的细节。虽然从生物体到原子水平的成像前景似乎遥不可及，但现在确实存在涵盖几乎所有这些成像尺度的成像技术。越来越多的生物医学研究将来自不同尺度的不同成像技术的信息结合在一起，即多模态成像，以拼凑出比单独使用一种技术更全面的对问题的理解。然而，由于缺乏公众对这些数据的可访问性和用于表示将不同模式纳入登记所需信息的常用格式，成像数据的更广泛整合受到阻碍。考虑到问题的巨大范围、不同的用户群体和所需的资源，一次处理所有尺度的成像将是极具挑战性的。在涉及分子三维结构研究的分子结构生物学领域，结构公共存档的概念已经很好地建立起来，例如PDB（原子模型数据）和EMDB（来自电子显微镜（EM）实验的3D卷，包括电子断层扫描）得到了广泛的社区支持。因此，我们的策略是首先考虑细胞和分子成像尺度之间的整合，并与相关社区协商。我们组织了两次“专家”研讨会，邀请了主要专家和社区代表，并提出了具体建议，包括探索大型EM图像数据集的公共存档，开发可视化工具，提供集成的、以问题为中心的结构视图，将来自不同成像模式的信息拼凑在一起，应该首先针对的成像模式- 3D扫描电子显微镜（3DSEM），软x射线断层扫描（SXT）和相关的光学和电子显微镜（CLEM），以及一种格式的发展，以促进数据集成。在一个正在进行的mrc资助项目（授权MR/L007835； MOL2CELL）中，我们成功开发了EMPIAR——一个原始EM图像数据的公共存档，能够处理tb范围内的数据集。我们正在开发一个基于网络的可视化工具（体积浏览器），它提供了一个可公开访问的三维生物数据在细胞和分子尺度上的集成视图，这些数据来自EMDB和PDB档案，以及一种支持这些尺度之间一种形式集成的格式。在拟议的项目中，我们希望以MOL2CELL项目中开始的工作为基础，a)扩展EMPIAR中的存档，以包括对拟议成像模式的全面支持，b)扩展格式支持，以表示将不同模式纳入注册所需的信息，并使用它来改进和扩展Volume浏览器。c)开发主要显微镜中心的软件和数据管道，以方便将数据存入EMDB和EMPIAR，并提高所收集信息的质量和数量。虽然该项目的范围仅限于分子和细胞成像尺度，但其结果可能适用于其他成像方式。将新的成像模式纳入EMPIAR可以作为如何组织和建立公共存档的一个模型，开发的格式可以用于其他成像模式之间的数据集成，以及与其他成像尺度集成可视化的卷浏览器。此外，多模态成像数据资源的开发人员可以从开放访问项目中开发的软件和EMPIAR中的数据中获益。

Consider a scenario in which one could image a whole organism, and then progressively zoom in to the level of organs, tissue, cells, molecules and finally atoms, at each step revealing more detail. Although the prospect of scaling from the level of organisms to atoms may seem far-fetched, there now do exist imaging techniques to cover almost all of these imaging scales. There is a growing body of biomedical research where information from different imaging techniques at different scales are combined, i.e., multi-modal imaging, to piece together a more comprehensive understanding of a problem than can be obtained from one technique alone. However the wider integration of imaging data is hampered by the lack of public accessibility to this data and commonly used formats for representing the information required to bring the different modalities into register. To address all scales of imaging at once would be extremely challenging given the enormous scope of the problem, the disparate user communities and the resources required.In the field of molecular structural biology, which involves the study of the 3D structure of molecules, the concept of public archiving of structures is well established with archives such as the PDB (atomic model data) and EMDB (3D volumes derived from electron microscopy (EM) experiments including electron tomography) enjoying widespread community support. Our strategy has therefore been to first consider the integration between the cellular and molecular imaging scales in consultation with the relevant communities. We organized two 'expert' workshops inviting key specialists and community representatives which resulted in concrete recommendations including - exploring public archiving of large EM image datasets, the development of visualisation tools that provide an integrated, problem-centric view of structures piecing together information from the different imaging modalities, the imaging modalities which should be targeted first - 3D scanning electron microscopy (3DSEM), soft X-ray tomography (SXT) and correlative light and electron microscopy (CLEM) , and the development of a format to facilitate data integration. In an on-going MRC-funded project (grant MR/L007835; MOL2CELL) we have successfully developed EMPIAR - a public archive for raw EM image data, which is capable of handling data-sets in the terabyte range. We are developing a web-based visualisation tool (Volume browser) that provides an openly accessible integrated view of 3D biological data at the cellular and molecular scales derived from the EMDB and PDB archives, and a format that supports one form of integration between these scales. In the proposed project we want to build upon the work started in the MOL2CELL project and a) extend archiving in EMPIAR to include full support for the proposed imaging modalities, b) extend format support to represent the information required to bring the different modalities into register and use this to improve and extend the Volume browser, and c) develop software and data pipelines from major microscopy centres to facilitate data deposition to EMDB and EMPIAR and to improve the quality and quantity of the information collected.While the scope of the project is limited to the molecular and cellular imaging scales, the outcomes are potentially applicable to other imaging modalities. The inclusion of the new imaging modalities into EMPIAR can serve as one model for how public archiving can be organized and established, the format developed can be used for data integration between other imaging modalities and the Volume browser for integrated visualisation with other imaging scales. Furthermore developers of resources for multi-modal imaging data stand to gain from open access to the software developed in the project and the data in EMPIAR.