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eC-CLEM: flexible multidimensional registration software for correlative microscopies

Nature Methods

Authors: Perrine Paul-Gilloteaux, Xavier Heiligenstein, Martin Belle, Marie-Charlotte Domart, Banafshe Larijani, Lucy Collinson, Graça Raposo & Jean Salamero
Date: 2017-01-31 • PMID: 26725201 • DOI: 10.1038/nmeth.4170
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Correlative light and electron microscopy (CLEM) is becoming increasingly popular within the life sciences. The diversity of light microscopy (LM) and electron microscopy (EM) modalities has led researchers to develop a multitude of CLEM workflows tailored to different scientific investigations1, 2. Finding the corresponding area between LM and EM images can be facilitated with specific sample holders, finder grids, laser marks or pattern recognition1. However, for all these workflows, the accurate association of a fluorescent object with its corresponding ultrastructure from data sets differing in scales by several orders of magnitude remains a universal bottleneck. Although several software solutions to the problem of achieving accurate association have been proposed (Supplementary Note 1), there is currently no available open-access software to achieve high-accuracy localization independent of specific registration fiducials that also offer nonrigid registration both in two and three dimensions (2D and 3D) and semisupervised registration.