Uncovering the molecular machinery of the human spindle-an integration of wet and dry systems biology

Rojas, Ana M. and Santamaria, Anna and Malik, Rainer and Jensen, Thomas Skøt and Körner, Roman and Morilla, Ian and de Juan, David and Krallinger, Martin and Hansen, Daniel Aaen and Hoffmann, Robert and Lees, Jonathan and Reid, Adam and Yeats, Corin and Wehner, Anja and Elowe, Sabine and Clegg, Andrew B. and Brunak, Søren and Nigg, Erich A. and Orengo, Christine and Valencia, Alfonso and Ranea, Juan A. G.. (2012) Uncovering the molecular machinery of the human spindle-an integration of wet and dry systems biology. PLoS ONE, 7 (3). e31813.

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Official URL: http://edoc.unibas.ch/47378/

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The mitotic spindle is an essential molecular machine involved in cell division, whose composition has been studied extensively by detailed cellular biology, high-throughput proteomics, and RNA interference experiments. However, because of its dynamic organization and complex regulation it is difficult to obtain a complete description of its molecular composition. We have implemented an integrated computational approach to characterize novel human spindle components and have analysed in detail the individual candidates predicted to be spindle proteins, as well as the network of predicted relations connecting known and putative spindle proteins. The subsequent experimental validation of a number of predicted novel proteins confirmed not only their association with the spindle apparatus but also their role in mitosis. We found that 75% of our tested proteins are localizing to the spindle apparatus compared to a success rate of 35% when expert knowledge alone was used. We compare our results to the previously published MitoCheck study and see that our approach does validate some findings by this consortium. Further, we predict so-called "hidden spindle hub", proteins whose network of interactions is still poorly characterised by experimental means and which are thought to influence the functionality of the mitotic spindle on a large scale. Our analyses suggest that we are still far from knowing the complete repertoire of functionally important components of the human spindle network. Combining integrated bio-computational approaches and single gene experimental follow-ups could be key to exploring the still hidden regions of the human spindle system.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Cell Biology (Nigg)
UniBasel Contributors:Nigg, Erich A.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Public Library of Science
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 Aug 2018 06:33
Deposited On:30 Nov 2017 10:51

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