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Uncovering the Molecular Machinery of the Human Spindle—An Integration of Wet and Dry Systems Biology

Author

Listed:
  • Ana M Rojas
  • Anna Santamaria
  • Rainer Malik
  • Thomas Skøt Jensen
  • Roman Körner
  • Ian Morilla
  • David de Juan
  • Martin Krallinger
  • Daniel Aaen Hansen
  • Robert Hoffmann
  • Jonathan Lees
  • Adam Reid
  • Corin Yeats
  • Anja Wehner
  • Sabine Elowe
  • Andrew B Clegg
  • Søren Brunak
  • Erich A Nigg
  • Christine Orengo
  • Alfonso Valencia
  • Juan A G Ranea

Abstract

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.

Suggested Citation

  • Ana M Rojas & Anna Santamaria & Rainer Malik & Thomas Skøt Jensen & Roman Körner & Ian Morilla & David de Juan & Martin Krallinger & Daniel Aaen Hansen & Robert Hoffmann & Jonathan Lees & Adam Reid & , 2012. "Uncovering the Molecular Machinery of the Human Spindle—An Integration of Wet and Dry Systems Biology," PLOS ONE, Public Library of Science, vol. 7(3), pages 1-16, March.
    • Handle: RePEc:plo:pone00:0031813
    DOI: 10.1371/journal.pone.0031813
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    References listed on IDEAS

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    1. Juan A G Ranea & Ian Morilla & Jon G Lees & Adam J Reid & Corin Yeats & Andrew B Clegg & Francisca Sanchez-Jimenez & Christine Orengo, 2010. "Finding the “Dark Matter” in Human and Yeast Protein Network Prediction and Modelling," PLOS Computational Biology, Public Library of Science, vol. 6(9), pages 1-14, September.
    2. David J. Sharp & Gregory C. Rogers & Jonathan M. Scholey, 2000. "Microtubule motors in mitosis," Nature, Nature, vol. 407(6800), pages 41-47, September.
    3. Wenhui Zhao & Jan-Philipp Kruse & Yi Tang & Sung Yun Jung & Jun Qin & Wei Gu, 2008. "Negative regulation of the deacetylase SIRT1 by DBC1," Nature, Nature, vol. 451(7178), pages 587-590, January.
    4. Sayda M. Elbashir & Jens Harborth & Winfried Lendeckel & Abdullah Yalcin & Klaus Weber & Thomas Tuschl, 2001. "Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells," Nature, Nature, vol. 411(6836), pages 494-498, May.
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