Genome-scale metabolic models (GEMs) are increasingly applied to investigate the physiology not only of simple prokaryotes, but also eukaryotes, such as plants, characterized with compartmentalized cells of multiple types. While genome-scale models aim at including the entirety of known metabolic reactions, mounting evidence has indicated that only a subset of these reactions is active in a given context, including: developmental stage, cell type, or environment. As a result, several methods have been proposed to reconstruct context-specific models from existing genome-scale models by integrating various types of high-throughput data. Here we present a mathematical framework that puts all existing methods under one umbrella and provides the means to better understand their functioning, highlight similarities and differences, and to help users in selecting a most suitable method for an application.
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http://dx.doi.org/10.3389/fpls.2014.00491 | DOI Listing |
Cell Syst
December 2024
Center for Bioinformatics and Computational Medicine, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Program in Chemical Biology, University of Michigan, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address:
While proliferating cells optimize their metabolism to produce biomass, the metabolic objectives of cells that perform non-proliferative tasks are unclear. The opposing requirements for optimizing each objective result in a trade-off that forces single cells to prioritize their metabolic needs and optimally allocate limited resources. Here, we present single-cell optimization objective and trade-off inference (SCOOTI), which infers metabolic objectives and trade-offs in biological systems by integrating bulk and single-cell omics data, using metabolic modeling and machine learning.
View Article and Find Full Text PDFSynth Syst Biotechnol
December 2024
Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
, a widely utilized model organism, has seen continuous updates to its genome-scale metabolic model (GEM) to enhance the prediction performance for metabolic engineering and systems biology. This study presents an auxotrophy-based curation of the yeast GEM, enabling facile upgrades to yeast GEMs in future endeavors. We illustrated that the curation bolstered the predictive capability of the yeast GEM particularly in predicting auxotrophs without compromising accuracy in other simulations, and thus could be an effective manner for GEM refinement.
View Article and Find Full Text PDFPLoS Genet
December 2024
Laboratory of Genetics, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Advances in DNA sequencing technology and computation now enable genome-wide scans for natural selection to be conducted on unprecedented scales. By examining patterns of sequence variation among individuals, biologists are identifying genes and variants that affect fitness. Despite this progress, most population genetic methods for characterizing selection assume that variants mutate in a simple manner and at a low rate.
View Article and Find Full Text PDFSyst Biol
January 2025
Cornell University, Department of Entomology, Ithaca, NY 14853, USA.
While some relationships in phylogenomic studies have remained stable since the Sanger sequencing era, many challenging nodes remain, even with genome-scale data. Incongruence or lack of resolution in the phylogenomic era is frequently attributed to inadequate data modeling and analytical issues that lead to systematic biases. However, few studies investigate the potential for random error or establish expectations for the level of resolution achievable with a given empirical dataset and integrate uncertainties across methods when faced with conflicting results.
View Article and Find Full Text PDFPLoS Comput Biol
January 2025
Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, California, United States of America.
The denitrifying bacterium Thauera sp. MZ1T, a common member of microbial communities in wastewater treatment facilities, can produce different compounds from a range of carbon (C) and nitrogen (N) sources under aerobic and anaerobic conditions. In these different conditions, Thauera modifies its metabolism to produce different compounds that influence the microbial community.
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