Contextual automated 3D analysis of subcellular organelles adapted to high-content screening

Thierry Dorval, Arnaud Ogier, Auguste Genovesio, Kuyon Lim Hye Kuyon Lim, Yoon Kwon Do Yoon Kwon, Joo Hyun Lee, Howard J. Worman, William Dauer, Regis Grailhe

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Advances in automated imaging microscopy allow fast acquisitions of multidimensional biological samples. Those microscopes open new possibilities for analyzing subcellular structures and spatial cellular arrangements. In this article, the authors describe a 3D image analysis framework adapted to medium-throughput screening. Upon adaptive and regularized segmentation, followed by precise 3D reconstruction, they achieve automatic quantification of numerous relevant 3D descriptors related to the shape, texture, and fluorescence intensity of multiple stained subcellular structures. A global analysis of the 3D reconstructed scene shows additional possibilities to quantify the relative position of organelles. Implementing this methodology, the authors analyzed the subcellular reorganization of the nucleus, the Golgi apparatus, and the centrioles occurring during the cell cycle. In addition, they quantified the effect of a genetic mutation associated with the early onset primary dystonia on the redistribution of torsinA from the bulk endoplasmic reticulum to the perinuclear space of the nuclear envelope. They show that their method enables the classification of various translocation levels of torsinA and opens the possibility for compound-based screening campaigns restoring the normal torsinA phenotype.

Original languageEnglish (US)
Pages (from-to)847-857
Number of pages11
JournalJournal of Biomolecular Screening
Volume15
Issue number7
DOIs
StatePublished - Aug 1 2010
Externally publishedYes

Keywords

  • automation
  • image analysis
  • image-based screening
  • phenotypic classification

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biotechnology
  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

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  • Cite this

    Dorval, T., Ogier, A., Genovesio, A., Hye Kuyon Lim, K. L., Do Yoon Kwon, Y. K., Lee, J. H., Worman, H. J., Dauer, W., & Grailhe, R. (2010). Contextual automated 3D analysis of subcellular organelles adapted to high-content screening. Journal of Biomolecular Screening, 15(7), 847-857. https://doi.org/10.1177/1087057110374993