Robust and automated detection of subcellular morphological motifs in 3D microscopy images
Robust and automated detection of subcellular morphological motifs in 3D microscopy images
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DOI：
10.1038/s41592-019-0539-z
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发表时间：
2019-10-01
期刊：
影响因子：
48
通讯作者：
Danuser, Gaudenz
中科院分区：
文献类型：
--
作者：
Driscoll, Meghan K.;Welf, Erik S.;Danuser, Gaudenz
活细胞三维（3D）显微镜的快速发展使细胞形态和信号的成像具有前所未有的细节。然而，系统地测量和可视化细胞内信号传导，细胞骨架组织和下游细胞形态输出之间的复杂关系的工具并不存在。在这里，我们介绍了u-shape 3D，这是一种计算机图形和机器学习管道，用于探测3D细胞形态发生背后的分子机制，并测试形态发生本身影响细胞内信号传导的有趣可能性。我们展示了一个通用的形态图案检测器，自动发现板状伪足，丝状伪足，水泡和其他图案。结合基序检测和分子定位，我们测量了PIP 2和Kras（V12）与水泡的差异相关性。这两种信号都与水泡边缘相关，正如膜定位蛋白所预期的那样，但只有PIP 2在水泡上增强。这表明，亚细胞信号传导过程的差异调制的局部形态图案。总的来说，我们的计算工作流程能够对细胞形状和信号传导的耦合进行客观的3D分析。
Rapid developments in live-cell three-dimensional (3D) microscopy enable imaging of cell morphology and signaling with unprecedented detail. However, tools to systematically measure and visualize the intricate relationships between intracellular signaling, cytoskeletal organization and downstream cell morphological outputs do not exist. Here, we introduce u-shape3D, a computer graphics and machine-learning pipeline to probe molecular mechanisms underlying 3D cell morphogenesis and to test the intriguing possibility that morphogenesis itself affects intracellular signaling. We demonstrate a generic morphological motif detector that automatically finds lamellipodia, filopodia, blebs and other motifs. Combining motif detection with molecular localization, we measure the differential association of PIP2 and Kras(V12) with blebs. Both signals associate with bleb edges, as expected for membrane-localized proteins, but only PIP2 is enhanced on blebs. This indicates that subcellular signaling processes are differentially modulated by local morphological motifs. Overall, our computational workflow enables the objective, 3D analysis of the coupling of cell shape and signaling.