Uncovering the molecular machinery of the human spindle--an integration of wet and dry systems biology
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Uncovering the molecular machinery of the human spindle--an integration of wet and dry systems biology. / 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.
In: P L o S One, Vol. 7, No. 3, 2012, p. e31813.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Uncovering the molecular machinery of the human spindle--an integration of wet and dry systems biology
AU - Rojas, Ana M
AU - Santamaria, Anna
AU - Malik, Rainer
AU - Jensen, Thomas Skøt
AU - Körner, Roman
AU - Morilla, Ian
AU - de Juan, David
AU - Krallinger, Martin
AU - Hansen, Daniel Aaen
AU - Hoffmann, Robert
AU - Lees, Jonathan
AU - Reid, Adam
AU - Yeats, Corin
AU - Wehner, Anja
AU - Elowe, Sabine
AU - Clegg, Andrew B
AU - Brunak, Søren
AU - Nigg, Erich A
AU - Orengo, Christine
AU - Valencia, Alfonso
AU - Ranea, Juan A G
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pone.0031813
DO - 10.1371/journal.pone.0031813
M3 - Journal article
C2 - 22427808
VL - 7
SP - e31813
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 3
ER -
ID: 40804019