Department of Pharmaceutical Sciences, University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, MI 48109, USA.
J Cheminform. 2013 Oct 5;5(1):44. doi: 10.1186/1758-2946-5-44.
To study the chemical determinants of small molecule transport inside cells, it is crucial to visualize relationships between the chemical structure of small molecules and their associated subcellular distribution patterns. For this purpose, we experimented with cells incubated with a synthetic combinatorial library of fluorescent, membrane-permeant small molecule chemical agents. With an automated high content screening instrument, the intracellular distribution patterns of these chemical agents were microscopically captured in image data sets, and analyzed off-line with machine vision and cheminformatics algorithms. Nevertheless, it remained challenging to interpret correlations linking the structure and properties of chemical agents to their subcellular localization patterns in large numbers of cells, captured across large number of images.
To address this challenge, we constructed a Multidimensional Online Virtual Image Display (MOVID) visualization platform using off-the-shelf hardware and software components. For analysis, the image data set acquired from cells incubated with a combinatorial library of fluorescent molecular probes was sorted based on quantitative relationships between the chemical structures, physicochemical properties or predicted subcellular distribution patterns. MOVID enabled visual inspection of the sorted, multidimensional image arrays: Using a multipanel desktop liquid crystal display (LCD) and an avatar as a graphical user interface, the resolution of the images was automatically adjusted to the avatar's distance, allowing the viewer to rapidly navigate through high resolution image arrays, zooming in and out of the images to inspect and annotate individual cells exhibiting interesting staining patterns. In this manner, MOVID facilitated visualization and interpretation of quantitative structure-localization relationship studies. MOVID also facilitated direct, intuitive exploration of the relationship between the chemical structures of the probes and their microscopic, subcellular staining patterns.
MOVID can provide a practical, graphical user interface and computer-assisted image data visualization platform to facilitate bioimage data mining and cheminformatics analysis of high content, phenotypic screening experiments.
为了研究小分子在细胞内运输的化学决定因素，将小分子的化学结构与其相关的亚细胞分布模式之间的关系可视化至关重要。为此，我们用合成的组合文库荧光膜渗透小分子化学试剂孵育细胞进行实验。通过自动化高通量筛选仪器，以图像数据集的形式微观捕获这些化学试剂在细胞内的分布模式，并通过机器视觉和化学信息学算法离线分析。然而，在大量细胞中解释将化学试剂的结构和性质与其亚细胞定位模式联系起来的相关性仍然具有挑战性，需要从大量图像中捕获。
为了解决这个挑战，我们使用现成的硬件和软件组件构建了一个多维在线虚拟图像显示（MOVID）可视化平台。用于分析，从用组合文库荧光分子探针孵育的细胞中获取的图像数据集是根据化学结构、物理化学性质或预测的亚细胞分布模式之间的定量关系进行排序的。MOVID 能够对排序后的多维图像阵列进行目视检查：使用多面板台式液晶显示器（LCD）和一个化身作为图形用户界面，根据化身的距离自动调整图像的分辨率，允许查看者快速浏览高分辨率图像阵列，放大和缩小图像以检查和注释显示出有趣染色模式的个别细胞。通过这种方式，MOVID 促进了定量结构定位关系研究的可视化和解释。MOVID 还促进了探针的化学结构与其微观亚细胞染色模式之间关系的直接直观探索。
MOVID 可以提供实用的图形用户界面和计算机辅助图像数据可视化平台，以促进高内涵表型筛选实验的生物图像数据挖掘和化学信息学分析。
