Uncovering the molecular machinery of the human spindle--an integration of wet and dry systems biology
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 diffic...
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| Veröffentlicht in: | PloS one 2012-03, Vol.7 (3), p.e31813-e31813 |
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| creator | Rojas, Ana M Santamaria, Anna Malik, Rainer Jensen, Thomas Skøt Körner, Roman Morilla, Ian de Juan, David Krallinger, Martin Hansen, Daniel Aaen Hoffmann, Robert Lees, Jonathan Reid, Adam Yeats, Corin Wehner, Anja Elowe, Sabine Clegg, Andrew B Brunak, Søren Nigg, Erich A Orengo, Christine Valencia, Alfonso Ranea, Juan A G |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0031813 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0031813</identifier><identifier>PMID: 22427808</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Biochemistry ; Bioinformatics ; Biology ; Cell adhesion & migration ; Cell cycle ; Cell Cycle Proteins - metabolism ; Cell division ; Chromosomes ; Computation ; Computational Biology - methods ; Computer applications ; Consortia ; Data Mining ; Databases, Protein ; Experiments ; Genes ; HeLa Cells ; Humans ; Hyperlinks ; Information theory ; Machinery and equipment ; Microscopy, Fluorescence ; Mitosis ; Molecular biology ; Molecular machines ; Neural networks ; Online data bases ; Plasmids - genetics ; Protein Interaction Mapping - methods ; Protein Structure, Tertiary ; Proteins ; Proteomics ; Proteomics - methods ; PubMed ; Ribonucleic acid ; RNA ; RNA, Small Interfering - genetics ; RNA-mediated interference ; Sensitivity and Specificity ; Spindle Apparatus - metabolism ; Transfection ; Tumors</subject><ispartof>PloS one, 2012-03, Vol.7 (3), p.e31813-e31813</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Rojas et al. 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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. 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| ispartof | PloS one, 2012-03, Vol.7 (3), p.e31813-e31813 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1323990568 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Analysis Biochemistry Bioinformatics Biology Cell adhesion & migration Cell cycle Cell Cycle Proteins - metabolism Cell division Chromosomes Computation Computational Biology - methods Computer applications Consortia Data Mining Databases, Protein Experiments Genes HeLa Cells Humans Hyperlinks Information theory Machinery and equipment Microscopy, Fluorescence Mitosis Molecular biology Molecular machines Neural networks Online data bases Plasmids - genetics Protein Interaction Mapping - methods Protein Structure, Tertiary Proteins Proteomics Proteomics - methods PubMed Ribonucleic acid RNA RNA, Small Interfering - genetics RNA-mediated interference Sensitivity and Specificity Spindle Apparatus - metabolism Transfection Tumors |
| title | Uncovering the molecular machinery of the human spindle--an integration of wet and dry systems biology |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T22%3A56%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Uncovering%20the%20molecular%20machinery%20of%20the%20human%20spindle--an%20integration%20of%20wet%20and%20dry%20systems%20biology&rft.jtitle=PloS%20one&rft.au=Rojas,%20Ana%20M&rft.date=2012-03-09&rft.volume=7&rft.issue=3&rft.spage=e31813&rft.epage=e31813&rft.pages=e31813-e31813&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0031813&rft_dat=%3Cgale_plos_%3EA477145237%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1323990568&rft_id=info:pmid/22427808&rft_galeid=A477145237&rft_doaj_id=oai_doaj_org_article_70153f80d41f49f28dad5fc2de9963d1&rfr_iscdi=true |