Improving the iMM904 S. cerevisiae metabolic model using essentiality and synthetic lethality data

<p>Abstract</p> <p>Background</p> <p><it>Saccharomyces cerevisiae </it>is the first eukaryotic organism for which a multi-compartment genome-scale metabolic model was constructed. Since then a sequence of improved metabolic reconstructions for yeast has been introduced. These metabolic models have been extensively used to elucidate the organizational principles of yeast metabolism and drive yeast strain engineering strategies for targeted overproductions. They have also served as a starting point and a benchmark for the reconstruction of genome-scale metabolic models for other eukaryotic organisms. In spite of the successive improvements in the details of the described metabolic processes, even the recent yeast model (i.e., <it>i</it>MM904) remains significantly less predictive than the latest <it>E. coli </it>model (i.e., <it>i</it>AF1260). This is manifested by its significantly lower specificity in predicting the outcome of grow/no grow experiments in comparison to the <it>E. coli </it>model.</p> <p>Results</p> <p>In this paper we make use of the automated GrowMatch procedure for restoring consistency with single gene deletion experiments in yeast and extend the procedure to make use of synthetic lethality data using the genome-scale model <it>i</it>MM904 as a basis. We identified and vetted using literature sources 120 distinct model modifications including various regulatory constraints for minimal and YP media. The incorporation of the suggested modifications led to a substantial increase in the fraction of correctly predicted lethal knockouts (i.e., specificity) from 38.84% (87 out of 224) to 53.57% (120 out of 224) for the minimal medium and from 24.73% (45 out of 182) to 40.11% (73 out of 182) for the YP medium. Synthetic lethality predictions improved from 12.03% (16 out of 133) to 23.31% (31 out of 133) for the minimal medium and from 6.96% (8 out of 115) to 13.04% (15 out of 115) for the YP medium.</p> <p>Conclusions</p> <p>Overall, this study provides a roadmap for the computationally driven correction of multi-compartment genome-scale metabolic models and demonstrates the value of synthetic lethals as curation agents.</p

Detailed process design based on genomics of survivors of food preservation processes

The food processing industry is faced with an ever-increasing demand for safe and minimally processed wholesome foods. In order to come to a knowledge-based rather than a mainly empirical combination of appropriate preservation hurdles, we will introduce the application of the recently booming genomics technology in food processing. Two examples of actual application will be discussed in some detail. (C) 2002 Elsevier Science Ltd. All rights reserved.</p

Emergence of sprite streamers from screening-ionization waves in the lower ionosphere

Sprite discharges above thunderclouds at altitudes of 40-90 km (refs1-5) are usually created by a strong positive cloud-to-ground lightning flash6. Sometimes these sprite discharges emerge from a visible halo 5,7-9, and during the first stage they always propagate downwards and branch on their way 5,7,9-11. Modelling efforts have been restricted to conditions of non-ionized air of constant density and show double-headed sprites12 or sprites starting from metal electrodes, but they do not explain why observations exclusively record sprites that propagate downwards. Here we present simulations with a numerical discharge model on a non-uniform, dynamically adapted computational grid13 to capture the wide range of emerging spatial scales, and we use realistic air and electron densities that vary with altitude. Our model shows a downward-propagating screening-ionization wave in the lower ionosphere that sharpens and collapses into a sprite streamer as it propagates farther down. Streamer velocity, diameter and length until branching agree with observations9 within measuring accuracy. We speculate that sprites generically emerge through the collapse of a wide screening-ionization wave into a sprite streamer, although this wave is only sometimes visible as a luminous halo. © 2009 Macmillan Publishers Limited. All rights reserved