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Kiri Choi

Publications and source records attributed to Kiri Choi.

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Tellurium: A Python Based Modeling and Reproducibility Platform for Systems Biology

In this article, we present Tellurium, a powerful Python-based integrated environment designed for model building, analysis, simulation and reproducibility in systems and synthetic biology. Tellurium is a modular, cross-platform, and open-source integrated development environment (IDE) composed of multiple libraries, plugins, and specialized modules and methods. Tellurium ensures exchangeability and reproducibility of computational models by supporting SBML (Systems Biology Markup Language), SED-ML (Simulation Experiment Description Markup Language), the COMBINE archive, and SBOL (Synthetic Biology Open Language). Tellurium is a self-contained modeling platform which comes with a fully configured Python distribution independent of other local Python installations on the target machine. The main interface is based on the Spyder IDE which has a highly accessible user interface akin to MATLAB (https://www.mathworks.com/). Tellurium uses libRoadRunner as the default SBML simulation engine due to its superior performance, scalability and ease of integration. libRoadRunner supports deterministic simulations, stochastic simulations and steady state analyses. Tellurium also includes Antimony, a human-readable model definition language which can be converted to and from SBML. Other standard Python scientific libraries such as NumPy, SciPy, and matplotlib are included by default. Additionally, we include several user-friendly plugins and advanced modules for a wide-variety of applications, ranging from visualization tools to complex algorithms for bifurcation analysis and multi-dimensional parameter scanning. By combining multiple libraries, plugins, and modules into a single package, Tellurium provides a unified but extensible solution for biological modeling and simulation.

Systems Biology

A portable library to support the SBML Layout Extension

1The SBML layout extension enables SBML models to encode layout information which describes the graphical depiction of model elements. In this application note, we describe libSBNW, a portable library that supports the SBML layout extension and can automatically generate layout for SBML models. The library can be used to automatically generate layout information for SBML models lacking it, or to edit coordinate information already encoded in a model. We provide C and Python APIs to allow other applications to host the library or to use it directly from the Python console. We show that the library is sufficient for creating a graphical application for displaying and editing layout information. The library is open-source and licensed under the BSD 3-clause license. Project source code, downloads, documentation and binaries for Windows and Mac OS X are available at https://github.com/sys-bio/sbnw. The library is also included in Tellurium, available at http://tellurium.analogmachine.org/. Video tutorials are available at http://0u812.github.io/sbnw/tutorials/.

Systems Biology

Controlling E. coli gene expression noise

Intracellular protein copy numbers show significant cell-to-cell variability within an isogenic population due to the random nature of biological reactions. Here we show how the variability in copy number can be controlled by perturbing gene expression. Depending on the genetic network and host, different perturbations can be applied to control variability. To understand more fully how noise propagates and behaves in biochemical networks we developed stochastic control analysis (SCA) which is a sensitivity-based analysis framework for the study of noise control. Here we apply SCA to synthetic gene expression systems encoded on plasmids that are transformed into Escherichia coli. We show that (1) dual control of transcription and translation efficiencies provides the most efficient way of noise-vs.-mean control. (2) The expressed proteins follow the gamma distribution function as found in chromosomal proteins. (3) One of the major sources of noise, leading to the cell-to-cell variability in protein copy numbers, is related to bursty translation. (4) By taking into account stochastic fluctuations in autofluorescence, the correct scaling relationship between the noise and mean levels of the protein copy numbers was recovered for the case of weak fluorescence signals.

Synthetic Biology