Uncovering the molecular machinery of the human spindle-an integration of wet and dry systems biology Journal Article
| Authors: | Rojas, A. M.; Santamaria, A.; Malik, R.; Jensen, T. S.; Körner, R.; Morilla, I.; de Juan, D.; Krallinger, M.; Hansen, D. A.; Hoffmann, R.; Lees, J.; Reid, A.; Yeats, C.; Wehner, A.; Elowe, S.; Clegg, A. B.; Brunak, S.; Nigg, E. A.; Orengo, C.; Valencia, A.; Ranea, J. A. G. |
| Article Title: | Uncovering the molecular machinery of the human spindle-an integration of wet and dry systems biology |
| 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. © 2012 Rojas et al. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; genetics; validation process; methodology; sensitivity and specificity; protein function; protein analysis; cell cycle protein; phenotype; metabolism; cell cycle proteins; cell division; apoptosis; biology; computational biology; protein protein interaction; protein; small interfering rna; rna, small interfering; hela cell; hela cells; transfection; proteomics; databases, protein; genetic transfection; data analysis; plasmid; cellular distribution; medline; plasmids; mitosis spindle; mitotic spindle apparatus; fluorescence microscopy; microscopy, fluorescence; protein structure, tertiary; molecular biology; protein structure; sequence homology; protein database; protein interaction mapping; protein tertiary structure; chromosome segregation; pubmed; machine learning; data mining; spindle hidden hub protein |
| Journal Title: | PLoS ONE |
| Volume: | 7 |
| Issue: | 3 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2012-01-01 |
| Start Page: | e31813 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0031813 |
| PROVIDER: | scopus |
| PMCID: | PMC3302876 |
| PUBMED: | 22427808 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 April 2012" - "Source: Scopus" |
