Genome-scale gene/reaction essentiality and synthetic lethality analysis Export

@article{citeulike:5470784, abstract = {Synthetic lethals are to pairs of non-essential genes whose simultaneous deletion prohibits growth. One can extend the concept of synthetic lethality by considering gene groups of increasing size where only the simultaneous elimination of all genes is lethal, whereas individual gene deletions are not. We developed optimization-based procedures for the exhaustive and targeted enumeration of multi-gene (and by extension multi-reaction) lethals for genome-scale metabolic models. Specifically, these approaches are applied to iAF1260, the latest model of Escherichia coli, leading to the complete identification of all double and triple gene and reaction synthetic lethals as well as the targeted identification of quadruples and some higher-order ones. Graph representations of these synthetic lethals reveal a variety of motifs ranging from hub-like to highly connected subgraphs providing a birds-eye view of the avenues available for redirecting metabolism and uncovering complex patterns of gene utilization and interdependence. The procedure also enables the use of falsely predicted synthetic lethals for metabolic model curation. By analyzing the functional classifications of the genes involved in synthetic lethals, we reveal surprising connections within and across clusters of orthologous group functional classifications.}, author = {Suthers, Patrick F. and Zomorrodi, Alireza and Maranas, Costas D.}, citeulike-article-id = {5470784}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/msb.2009.56}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/msb200956}, day = {18}, doi = {10.1038/msb.2009.56}, journal = {Molecular Systems Biology}, keywords = {metabolic, phenotype, reconstruction, synthetic\_lethality, systems}, month = {August}, posted-at = {2009-08-19 12:07:49}, priority = {3}, publisher = {Nature Publishing Group}, title = {Genome-scale gene/reaction essentiality and synthetic lethality analysis}, url = {http://dx.doi.org/10.1038/msb.2009.56}, volume = {5}, year = {2009} }

TY - JOUR ID - citeulike:5470784 L3 - citeulike-article-id:5470784 N2 - Synthetic lethals are to pairs of non-essential genes whose simultaneous deletion prohibits growth. One can extend the concept of synthetic lethality by considering gene groups of increasing size where only the simultaneous elimination of all genes is lethal, whereas individual gene deletions are not. We developed optimization-based procedures for the exhaustive and targeted enumeration of multi-gene (and by extension multi-reaction) lethals for genome-scale metabolic models. Specifically, these approaches are applied to iAF1260, the latest model of Escherichia coli, leading to the complete identification of all double and triple gene and reaction synthetic lethals as well as the targeted identification of quadruples and some higher-order ones. Graph representations of these synthetic lethals reveal a variety of motifs ranging from hub-like to highly connected subgraphs providing a birds-eye view of the avenues available for redirecting metabolism and uncovering complex patterns of gene utilization and interdependence. The procedure also enables the use of falsely predicted synthetic lethals for metabolic model curation. By analyzing the functional classifications of the genes involved in synthetic lethals, we reveal surprising connections within and across clusters of orthologous group functional classifications. JF - Molecular Systems Biology TI - Genome-scale gene/reaction essentiality and synthetic lethality analysis PB - Nature Publishing Group VL - 5 KW - metabolic KW - phenotype KW - reconstruction KW - synthetic_lethality KW - systems AU - Suthers, Patrick AU - Zomorrodi, Alireza AU - Maranas, Costas PY - 2009/08/18/ UR - http://dx.doi.org/10.1038/msb.2009.56 ER -