Rojas, AM;
Santamaria, A;
Malik, R;
Jensen, TS;
Körner, R;
Morilla, I;
de Juan, D;
... Ranea, JA; + view all
(2012)
Uncovering the molecular machinery of the human spindle--an integration of wet and dry systems biology.
PLoS One
, 7
(3)
, Article e31813. 10.1371/journal.pone.0031813.
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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.
| Type: | Article |
|---|---|
| Title: | Uncovering the molecular machinery of the human spindle--an integration of wet and dry systems biology. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0031813 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0031813 |
| Language: | English |
| Additional information: | © 2012 Rojas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3302876 This work was supported by ENFIN, a Network of Excellence funded by the European Commission within its FP6 Programme, under the thematic area “Life sciences, genomics and biotechnology for health,” contract number LSHG-CT-2005-518254. This project was also supported by Interaction Proteome (contract number LSHG-CT-2003-505520). AR is funded by Spanish Ministry of Science and Innovation FIS PS09/02111. AC acknowledges funding from the EMBRACE European Network of Excellence. AMR acknowledges funding from PS09/02111 from the Spanish Ministry of Science and Innovation. JAGR is funded by EU-FP7-Systems Microscopy NoE (grant agreement n°258068), by the SAF2009-09839 project and the Ramon y Cajal program (RYC-2007-01649) from Ministerio de Ciencia e Innovación, Spain. This study is also funded by FP7–HEALTH–2010-two-stage Grant Agreement Number 259348 ASSET: Analysing and Striking the Sensitivities of Embryonal Tumours (HEALTH-F4-2010-259348). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Keywords: | Cell Cycle Proteins, Computational Biology, Data Mining, Databases, Protein, HeLa Cells, Humans, Microscopy, Fluorescence, Mitotic Spindle Apparatus, Plasmids, Protein Interaction Mapping, Protein Structure, Tertiary, Proteomics, PubMed, RNA, Small Interfering, Sensitivity and Specificity, Transfection |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1346199 |
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