Subscribe: CiteULike: raiyar's Thorsson
Preview: CiteULike: raiyar's Thorsson

CiteULike: raiyar's Thorsson

CiteULike: raiyar's Thorsson


A Predictive Model for Transcriptional Control of Physiology in a Free Living Cell


Cell, Vol. 131, No. 7. (17 September 2015), pp. 1354-1365, doi:10.1016/j.cell.2007.10.053

The environment significantly influences the dynamic expression and assembly of all components encoded in the genome of an organism into functional biological networks. We have constructed a model for this process in Halobacterium salinarum NRC-1 through the data-driven discovery of regulatory and functional interrelationships among ?80% of its genes and key abiotic factors in its hypersaline environment. Using relative changes in 72 transcription factors and 9 environmental factors (EFs) this model accurately predicts dynamic transcriptional responses of all these genes in 147 newly collected experiments representing completely novel genetic backgrounds and environments?suggesting a remarkable degree of network completeness. Using this model we have constructed and tested hypotheses critical to this organism's interaction with its changing hypersaline environment. This study supports the claim that the high degree of connectivity within biological and EF networks will enable the construction of similar models for any organism from relatively modest numbers of experiments.
Richard Bonneau, Marc Facciotti, David Reiss, Amy Schmid, Min Pan, Amardeep Kaur, Vesteinn Thorsson, Paul Shannon, Michael Johnson, Christopher Bare, William Longabaugh, Madhavi Vuthoori, Kenia Whitehead, Aviv Madar, Lena Suzuki, Tetsuya Mori, Dong-Eun Chang, Jocelyne DiRuggiero, Carl Johnson, Leroy Hood, Nitin Baliga

Integrated Genomic and Proteomic Analyses of a Systematically Perturbed Metabolic Network


Science In Science, Vol. 292, No. 5518. (04 May 2001), pp. 929-934, doi:10.1126/science.292.5518.929

We demonstrate an integrated approach to build, test, and refine a model of a cellular pathway, in which perturbations to critical pathway components are analyzed using DNA microarrays, quantitative proteomics, and databases of known physical interactions. Using this approach, we identify 997 messenger RNAs responding to 20 systematic perturbations of the yeast galactose-utilization pathway, provide evidence that approximately 15 of 289 detected proteins are regulated posttranscriptionally, and identify explicit physical interactions governing the cellular response to each perturbation. We refine the model through further iterations of perturbation and global measurements, suggesting hypotheses about the regulation of galactose utilization and physical interactions between this and a variety of other metabolic pathways.
Trey Ideker, Vesteinn Thorsson, Jeffrey Ranish, Rowan Christmas, Jeremy Buhler, Jimmy Eng, Roger Bumgarner, David Goodlett, Ruedi Aebersold, Leroy Hood