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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: 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
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2012
Materias:
R
Q
Acceso en línea:https://doaj.org/article/70153f80d41f49f28dad5fc2de9963d1
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:70153f80d41f49f28dad5fc2de9963d1
record_format dspace
spelling oai:doaj.org-article:70153f80d41f49f28dad5fc2de9963d12021-11-18T07:25:40ZUncovering the molecular machinery of the human spindle--an integration of wet and dry systems biology.1932-620310.1371/journal.pone.0031813https://doaj.org/article/70153f80d41f49f28dad5fc2de9963d12012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22427808/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Ana M RojasAnna SantamariaRainer MalikThomas Skøt JensenRoman KörnerIan MorillaDavid de JuanMartin KrallingerDaniel Aaen HansenRobert HoffmannJonathan LeesAdam ReidCorin YeatsAnja WehnerSabine EloweAndrew B CleggSøren BrunakErich A NiggChristine OrengoAlfonso ValenciaJuan A G RaneaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e31813 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
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
Uncovering the molecular machinery of the human spindle--an integration of wet and dry systems biology.
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.
format article
author 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
author_facet 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
author_sort Ana M Rojas
title Uncovering the molecular machinery of the human spindle--an integration of wet and dry systems biology.
title_short Uncovering the molecular machinery of the human spindle--an integration of wet and dry systems biology.
title_full Uncovering the molecular machinery of the human spindle--an integration of wet and dry systems biology.
title_fullStr Uncovering the molecular machinery of the human spindle--an integration of wet and dry systems biology.
title_full_unstemmed Uncovering the molecular machinery of the human spindle--an integration of wet and dry systems biology.
title_sort uncovering the molecular machinery of the human spindle--an integration of wet and dry systems biology.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/70153f80d41f49f28dad5fc2de9963d1
work_keys_str_mv AT anamrojas uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
AT annasantamaria uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
AT rainermalik uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
AT thomasskøtjensen uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
AT romankorner uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
AT ianmorilla uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
AT daviddejuan uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
AT martinkrallinger uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
AT danielaaenhansen uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
AT roberthoffmann uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
AT jonathanlees uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
AT adamreid uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
AT corinyeats uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
AT anjawehner uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
AT sabineelowe uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
AT andrewbclegg uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
AT sørenbrunak uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
AT erichanigg uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
AT christineorengo uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
AT alfonsovalencia uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
AT juanagranea uncoveringthemolecularmachineryofthehumanspindleanintegrationofwetanddrysystemsbiology
_version_ 1718423480621334528