Browsing by Author "Vidal-Cespedes, Carlos"

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    Accurate characterization of dynamic microbial gene expression and growth rate profiles
    (2022) Vidal, Gonzalo; Vidal-Cespedes, Carlos; Silva, Macarena Munoz; Castillo-Passi, Carlos; Feliu, Guillermo Yanez; Federici, Fernan; Rudge, Timothy J.
    Genetic circuits are subject to variability due to cellular and compositional contexts. Cells face changing internal states and environments, the cellular context, to which they sense and respond by changing their gene expression and growth rates. Furthermore, each gene in a genetic circuit operates in a compositional context of genes which may interact with each other and the host cell in complex ways. The context of genetic circuits can, therefore, change gene expression and growth rates, and measuring their dynamics is essential to understanding natural and synthetic regulatory networks that give rise to functional phenotypes. However, reconstruction of microbial gene expression and growth rate profiles from typical noisy measurements of cell populations is difficult due to the effects of noise at low cell densities among other factors. We present here a method for the estimation of dynamic microbial gene expression rates and growth rates from noisy measurement data. Compared to the current state-of-the-art, our method significantly reduced the mean squared error of reconstructions from simulated data of growth and gene expression rates, improving the estimation of timing and magnitude of relevant shapes of profiles. We applied our method to characterize a triple-reporter plasmid library combining multiple transcription units in different compositional and cellular contexts in Escherichia coli. Our analysis reveals cellular and compositional context effects on microbial growth and gene expression rate dynamics and suggests a method for the dynamic ratiometric characterization of constitutive promoters relative to an in vivo reference.
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    LOICA: Integrating Models with Data for Genetic Network Design Automation
    (2022) Vidal, Gonzalo; Vidal-Cespedes, Carlos; Rudge, Timothy J.
    Genetic design automation tools are necessary to expand the scale and complexity of possible synthetic genetic networks. These tools are enabled by abstraction of a hierarchy of standardized components and devices. Abstracted elements must be parametrized from data derived from relevant experiments, and these experiments must be related to the part composition of the abstract components. Here we present Logical Operators for Integrated Cell Algorithms (LOICA), a Python package for designing, modeling, and characterizing genetic networks based on a simple object-oriented design abstraction. LOICA uses classes to represent different biological and experimental components, which generate models through their interactions. These models can be parametrized by direct connection to data contained in Flapjack so that abstracted components of designs can characterize themselves. Models can be simulated using continuous or stochastic methods and the data published and managed using Flapjack. LOICA also outputs SBOL3 descriptions and generates graph representations of genetic network designs.