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Model-based redesign of global transcription regulation.

ABSTRACT: Synthetic biology aims to the design or redesign of biological systems. In particular, one possible goal could be the rewiring of the transcription regulation network by exchanging the endogenous promoters. To achieve this objective, we have adapted current methods to the inference of a model based on ordinary differential equations that is able to predict the network response after a major change in its topology. Our procedure utilizes microarray data for training. We have experimentally validated our inferred global regulatory model in Escherichia coli by predicting transcriptomic profiles under new perturbations. We have also tested our methodology in silico by providing accurate predictions of the underlying networks from expression data generated with artificial genomes. In addition, we have shown the predictive power of our methodology by obtaining the gene profile in experimental redesigns of the E. coli genome, where rewiring the transcriptional network by means of knockouts of master regulators or by upregulating transcription factors controlled by different promoters. Our approach is compatible with most network inference methods, allowing to explore computationally future genome-wide redesign experiments in synthetic biology.

SUBMITTER: Carrera J

PROVIDER: S-EPMC2655681 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Model-based redesign of global transcription regulation.

Carrera Javier J Rodrigo Guillermo G Jaramillo Alfonso A

Nucleic acids research 20090202 5

Synthetic biology aims to the design or redesign of biological systems. In particular, one possible goal could be the rewiring of the transcription regulation network by exchanging the endogenous promoters. To achieve this objective, we have adapted current methods to the inference of a model based on ordinary differential equations that is able to predict the network response after a major change in its topology. Our procedure utilizes microarray data for training. We have experimentally valida ...[more]

PMID: 19188257

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Project description:IntroductionThe purpose of the study is to investigate how community-based organizations perceive Medicaid policy changes to address the social determinants of health.MethodsThis study included 46 key informant interviews, representing 44 community-based organizations across Massachusetts conducted from September 2017 to March 2018. The interviews were designed to collect community-based organizations' perceptions of Medicaid policy changes. An Advisory Board was empaneled for feedback on data collection and analysis. Massachusetts was chosen as a study site in light of explicit policy efforts to incentivize healthcare organizations to take a more active role in social determinants of health, most notably through the creation of Medicaid Accountable Care Organizations.ResultsThe community-based organizations expressed optimism about future partnerships with healthcare organizations. This optimism existed alongside the recognition that healthcare organizations and community-based organizations can have conflicting agendas, including misaligned outcomes of interest and timelines. Community-based organizations struggled to define a clear strategy for partnership in the face of incomplete information about how the final Medicaid redesign would proceed and what healthcare providers would be looking for in a partner.ConclusionsChanges to Medicaid policy can catalyze interest in partnership between healthcare organizations and community-based organizations. To minimize the impact of conflicting agendas, policymakers and healthcare leadership should ensure community-based organizations are part of strategy development and social service program implementation.Supplement informationThis article is part of a supplement entitled Identifying and Intervening on Social Needs in Clinical Settings: Evidence and Evidence Gaps, which is sponsored by the Agency for Healthcare Research and Quality of the U.S. Department of Health and Human Services, Kaiser Permanente, and the Robert Wood Johnson Foundation.

Dataset Information

Model-based redesign of global transcription regulation.

Publications

Model-based redesign of global transcription regulation.

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