Journal article
Uncovering the Molecular Machinery of the Human Spindle-An Integration of Wet and Dry Systems Biology
Centro Nacional de Investigaciones Oncológicas1
Max Planck Institute2
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark3
University of Málaga4
Department of Systems Biology, Technical University of Denmark5
Memorial Sloan-Kettering Cancer Center6
University College London7
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark8
CFB - Metagenomic Systems Biology, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark9
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.
Language: | English |
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Publisher: | Public Library of Science |
Year: | 2012 |
Pages: | e31813 |
ISSN: | 19326203 |
Types: | Journal article |
DOI: | 10.1371/journal.pone.0031813 |
ASSEMBLY CHECKPOINT BIOLOGY CELL-CYCLE COMPLEX GENE-FUNCTION KINETOCHORE MAMMALIAN-CELLS MITOSIS MITOTIC PROGRESSION PLK1-DEPENDENT PHOSPHORYLATION PROTEIN
Cell Cycle Proteins Computational Biology Data Mining Databases, Protein HeLa Cells Humans Medicine Microscopy, Fluorescence Plasmids Protein Interaction Mapping Protein Structure, Tertiary Proteomics PubMed Q R RNA, Small Interfering Science Sensitivity and Specificity Spindle Apparatus Transfection