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'Differential visual proteomics': Enabling the proteome-wide comparison of protein structures of single-cells

Syntychaki, Anastasia and Rima, Luca and Schmidli, Claudio and Stohler, Thomas and Bieri, Andrej and Sütterlin, Rosmarie and Stahlberg, Henning and Castaño-Díez, Daniel and Braun, Thomas. (2019) 'Differential visual proteomics': Enabling the proteome-wide comparison of protein structures of single-cells. Journal of proteome research, 18 (9). pp. 3521-3531.

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Official URL: https://edoc.unibas.ch/71572/

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Abstract

Proteins are involved in all tasks of life, and their characterization is essential to understand the underlying mechanisms of biological processes. We present a method called 'differential visual proteomics' geared to study proteome-wide structural changes of proteins and protein-complexes between a disturbed and an undisturbed cell or between two cell populations. To implement this method, the cells are lysed and the lysate is prepared in a lossless manner for single-particle electron microscopy (EM). The samples are subsequently imaged in the EM. Individual particles are computationally extracted from the images and pooled together, while keeping track of which particle originated from which specimen. The extracted particles are then aligned and classified. A final quantitative analysis of the particle classes found identifies the particle structures that differ between positive and negative control samples. The algorithm and a graphical user interface developed to perform the analysis and to visualize the results were tested with simulated and experimental data. The results are presented and the potential and limitations of the current implementation are discussed. We envisage the method as a tool for the untargeted profiling of the structural changes in the proteome of single-cells as a response to a disturbing force.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Stahlberg)
UniBasel Contributors:Stahlberg, Henning
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society
ISSN:1535-3893
e-ISSN:1535-3907
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:17 Aug 2020 15:24
Deposited On:17 Aug 2020 15:24

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