Mapping the human phosphatome on growth pathways
Abstract Large‐scale siRNA screenings allow linking the function of poorly characterized genes to phenotypic readouts. According to this strategy, genes are associated with a function of interest if the alteration of their expression perturbs the phenotypic readouts. However, given the intricacy of...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2012-08-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb.2012.36 |
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| _version_ | 1849235601914593280 |
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| author | Francesca Sacco Pier Federico Gherardini Serena Paoluzi Julio Saez‐Rodriguez Manuela Helmer‐Citterich Antonella Ragnini‐Wilson Luisa Castagnoli Gianni Cesareni |
| author_facet | Francesca Sacco Pier Federico Gherardini Serena Paoluzi Julio Saez‐Rodriguez Manuela Helmer‐Citterich Antonella Ragnini‐Wilson Luisa Castagnoli Gianni Cesareni |
| author_sort | Francesca Sacco |
| collection | DOAJ |
| description | Abstract Large‐scale siRNA screenings allow linking the function of poorly characterized genes to phenotypic readouts. According to this strategy, genes are associated with a function of interest if the alteration of their expression perturbs the phenotypic readouts. However, given the intricacy of the cell regulatory network, the mapping procedure is low resolution and the resulting models provide little mechanistic insights. We have developed a new strategy that combines multiparametric analysis of cell perturbation with logic modeling to achieve a more detailed functional mapping of human genes onto complex pathways. A literature‐derived optimized model is used to infer the cell activation state following upregulation or downregulation of the model entities. By matching this signature with the experimental profile obtained in the high‐throughput siRNA screening it is possible to infer the target of each protein, thus defining its ‘entry point’ in the network. By this novel approach, 41 phosphatases that affect key growth pathways were identified and mapped onto a human epithelial cell‐specific growth model, thus providing insights into the mechanisms underlying their function. |
| format | Article |
| id | doaj-art-36fc0e83131b46deb8025865c26f2847 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2012-08-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-36fc0e83131b46deb8025865c26f28472025-08-20T04:02:44ZengSpringer NatureMolecular Systems Biology1744-42922012-08-018111510.1038/msb.2012.36Mapping the human phosphatome on growth pathwaysFrancesca Sacco0Pier Federico Gherardini1Serena Paoluzi2Julio Saez‐Rodriguez3Manuela Helmer‐Citterich4Antonella Ragnini‐Wilson5Luisa Castagnoli6Gianni Cesareni7Department of Biology, University of Rome ‘Tor Vergata’Department of Biology, University of Rome ‘Tor Vergata’Department of Biology, University of Rome ‘Tor Vergata’EMBL‐EBIDepartment of Biology, University of Rome ‘Tor Vergata’Department of Biology, University of Rome ‘Tor Vergata’Department of Biology, University of Rome ‘Tor Vergata’Department of Biology, University of Rome ‘Tor Vergata’Abstract Large‐scale siRNA screenings allow linking the function of poorly characterized genes to phenotypic readouts. According to this strategy, genes are associated with a function of interest if the alteration of their expression perturbs the phenotypic readouts. However, given the intricacy of the cell regulatory network, the mapping procedure is low resolution and the resulting models provide little mechanistic insights. We have developed a new strategy that combines multiparametric analysis of cell perturbation with logic modeling to achieve a more detailed functional mapping of human genes onto complex pathways. A literature‐derived optimized model is used to infer the cell activation state following upregulation or downregulation of the model entities. By matching this signature with the experimental profile obtained in the high‐throughput siRNA screening it is possible to infer the target of each protein, thus defining its ‘entry point’ in the network. By this novel approach, 41 phosphatases that affect key growth pathways were identified and mapped onto a human epithelial cell‐specific growth model, thus providing insights into the mechanisms underlying their function.https://doi.org/10.1038/msb.2012.36cancercomputational biologyfunctional genomicsimagingmodeling |
| spellingShingle | Francesca Sacco Pier Federico Gherardini Serena Paoluzi Julio Saez‐Rodriguez Manuela Helmer‐Citterich Antonella Ragnini‐Wilson Luisa Castagnoli Gianni Cesareni Mapping the human phosphatome on growth pathways Molecular Systems Biology cancer computational biology functional genomics imaging modeling |
| title | Mapping the human phosphatome on growth pathways |
| title_full | Mapping the human phosphatome on growth pathways |
| title_fullStr | Mapping the human phosphatome on growth pathways |
| title_full_unstemmed | Mapping the human phosphatome on growth pathways |
| title_short | Mapping the human phosphatome on growth pathways |
| title_sort | mapping the human phosphatome on growth pathways |
| topic | cancer computational biology functional genomics imaging modeling |
| url | https://doi.org/10.1038/msb.2012.36 |
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