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Interpretation of Genomic Variants Using a Unified Biological Network Approach

Ekta Khurana, Yao Fu, Jieming Chen, Mark Gerstein, Andrey Rzhetsky
2013 PLoS Computational Biology  
Integration of three-dimensional protein structures reveals that the correlation with centrality in the protein-protein interaction network is also seen in terms of the number of interaction interfaces  ...  However, this is not the case for metabolic pathways, where the highly central genes have more duplicated copies and are more tolerant to loss-of-function mutations.  ...  Acknowledgments We thank Chong Shou for help with obtaining the network data and construction of SIN. Author Contributions  ... 
doi:10.1371/journal.pcbi.1002886 pmid:23505346 pmcid:PMC3591262 fatcat:sgw6f2lr2nfujmz74ly7qglyqe

Analysis of omics data with genome-scale models of metabolism

Daniel R. Hyduke, Nathan E. Lewis, Bernhard Ø. Palsson
2013 Molecular Biosystems  
Szappanos et al. 35 used an SGA to measure the interactions of 613 metabolic genes to explore the utility of metabolic network models in investigating genetic interactions.  ...  , and nucleic acids) that operate simultaneously through a network of interactions to generate cellular functions and phenotypic states 1 .  ... 
doi:10.1039/c2mb25453k pmid:23247105 pmcid:PMC3594511 fatcat:27qsql7sk5hjtcg7quseuqis5u

Biological network analyses: computational genomics and systems approaches

S.P. Walton, Z. Li, C. Chan
2006 Molecular Simulation  
The complex responses of cells to stimuli are the aggregate of alterations at the genetic, protein, metabolic and cellular levels.  ...  The integration of such data for the computational elucidation and analysis of cellular pathways and networks is an area of considerable current interest.  ...  Acknowledgements The authors gratefully acknowledge support from the National Science Foundation (BES 0222747, BES 0331297, and BES 0425821), the Environmental  ... 
doi:10.1080/08927020600647052 fatcat:rluf4kjvubd4xphayjg5brozta

The Role of Protein Interactions in Mediating Essentiality and Synthetic Lethality

David Talavera, David L. Robertson, Simon C. Lovell, John Parkinson
2013 PLoS ONE  
interactions, rather than being inherent in gene and protein products themselves.  ...  We also find that essential genes and synthetic lethal pairs cluster in the protein-protein interaction network.  ...  Sherman for assistance on the DAVID analysis, and Kathyrn Hentges for critical reading of the manuscript.  ... 
doi:10.1371/journal.pone.0062866 pmid:23638160 pmcid:PMC3639263 fatcat:y23g4s7cxnbzfi5ligdgfwc2fu

Linking high-resolution metabolic flux phenotypes and transcriptional regulation in yeast modulated by the global regulator Gcn4p

J. F. Moxley, M. C. Jewett, M. R. Antoniewicz, S. G. Villas-Boas, H. Alper, R. T. Wheeler, L. Tong, A. G. Hinnebusch, T. Ideker, J. Nielsen, G. Stephanopoulos
2009 Proceedings of the National Academy of Sciences of the United States of America  
As a first step in linking metabolic control and genetic regulatory networks, this model underscores the importance of integrating diverse data types in large-scale cellular models.  ...  To address this limitation, we developed a model-based approach to correlate mRNA and metabolic flux data that combines information from both interaction network models and flux determination models.  ...  This work was supported by National Institutes of Health Grant 1R01 DK075850-01, the National Science Foundation International Research Fellowship Program, the Singapore-Massachusetts Institute of Technology  ... 
doi:10.1073/pnas.0811091106 pmid:19346491 pmcid:PMC2672541 fatcat:ynqb5ouarva3rdqpebvlowjm3m

Construction of Multiscale Genome-Scale Metabolic Models: Frameworks and Challenges

Xinyu Bi, Yanfeng Liu, Jianghua Li, Guocheng Du, Xueqin Lv, Long Liu
2022 Biomolecules  
Genome-scale metabolic models (GEMs) are effective tools for metabolic engineering and have been widely used to guide cell metabolic regulation.  ...  This review summarized the recent advances in the development of multiscale GEMs, including multiconstraint, multiomic, and whole-cell models, and outlined machine learning applications in GEM construction  ...  genetic interactions in small-molecule metabolism and establish a GEM performance range [140] .  ... 
doi:10.3390/biom12050721 pmid:35625648 pmcid:PMC9139095 fatcat:uqdglmzrnzgoheioxvpausmwt4

Bridging the Gap between Fluxomics and Industrial Biotechnology

Xueyang Feng, Lawrence Page, Jacob Rubens, Lauren Chircus, Peter Colletti, Himadri B. Pakrasi, Yinjie J. Tang
2010 Journal of Biomedicine and Biotechnology  
Second, the complexity of metabolic regulation poses a great challenge for precise prediction and analysis of metabolic networks, as there are gaps between fluxomics results and other omics studies.  ...  Metabolic flux analysis is a vital tool used to determine the ultimate output of cellular metabolism and thus detect biotechnologically relevant bottlenecks in productivity.13C-based metabolic flux analysis  ...  The authors are grateful to all of the students (Bing Wu, Arul Varman, Yin Wang, Stephanie Suen, Craig Jacobson, and Wenying Liu) in the 2010 Metabolic Engineering class (ChE596) at Washington University  ... 
doi:10.1155/2010/460717 pmid:21274256 pmcid:PMC3022177 fatcat:pj5azbtlkjgrxiefvgi43crgli

Genetic networks for the functional study of genomes

A. G. Pisabarro, G. Perez, J. L. Lavin, L. Ramirez
2008 Briefings in Functional Genomics & Proteomics  
in the same metabolic process, gene products interacting physically between them.  ...  The connections linking these genetic elements in the network reflect the genetic, physical and/or functional interaction among them.  ...  Acknowledgements This work has been supported by funds of the AGL2005-08005-C02-01 and GEN2006-27843-E, and by institutional support from the Public University of Navarre.  ... 
doi:10.1093/bfgp/eln026 pmid:18579617 fatcat:3fzho4tlfzey5bronfvzcylxpm

Systems biology in heart diseases

G E Louridas, I E Kanonidis, K G Lourida
2010 Hippokratia  
Systems biology based on integrative computational analysis and high technology is in a position to construct networks, to study the interactions between molecular components and to develop models of cardiac  ...  Clinical cardiology gets an integrated picture of parameters that are addressed to ventricular and vessel mechanics, cardiac metabolism and electrical activation.  ...  A cardiovascular metabolism network has been described that presented cardiovascular metabolism as an interactive and capable network of metabolites designed for regular and predictable energy delivery  ... 
pmid:20411053 pmcid:PMC2843564 fatcat:uftlhpfuszc53a423pngq7qydm

Constraining the metabolic genotype–phenotype relationship using a phylogeny of in silico methods

Nathan E. Lewis, Harish Nagarajan, Bernhard O. Palsson
2012 Nature Reviews Microbiology  
Constraint-based models of genome-scale metabolic networks capture the genotype-phenotype relationship by simultaneously accounting for constraints that are imposed on phenotype by physicochemical laws  ...  FIG. 1e) , and a genome-scale perspective of cell metabolism that accounts for all metabolic gene products in a cell (FIG. 1d,f) .  ...  Recently, high-throughput genetic-interaction screens have helped refine metabolic networks and the biomass objective function of yeast 79, 94 .  ... 
doi:10.1038/nrmicro2737 pmid:22367118 pmcid:PMC3536058 fatcat:ybk5wpy67fbcpnbg5azcu4rrse

Systems level modelling of metabolism in fungal endophytes - implications for the symbiosis with ryegrass

Rajiv Chaturvedi, Tanya Soboleva, Linda Johnson, Anthony Parsons, Susanne Rasmussen
2007 NZGA: Research and Practice Series  
We used constraint based stoichiometric modelling of metabolic fluxes in EpichloÃ" festucae (FL1), a targeted gene replacement of a non-ribosomal peptide synthetase (termed sidF) from E. festucae, and  ...  After constructing the metabolic network at a genome scale, we applied constraints on enzymatic reactions that require iron as co-factor to study the variations in metabolic network capabilities of the  ...  The novel aspects of our methodology in modelling metabolism on a genome scale are the manner in which we address (a) symbiotic interactions of metabolic networks of two species and (b) metabolism of genetic  ... 
doi:10.33584/rps.13.2006.3049 fatcat:atmntr542fguhl35exuppn52cq

Seeing the wood for the trees: a forest of methods for optimization and omic-network integration in metabolic modelling

Supreeta Vijayakumar, Max Conway, Pietro Lió, Claudio Angione
2017 Briefings in Bioinformatics  
Metabolic modelling has entered a mature phase with dozens of methods and software implementations available to the practitioner and the theoretician.  ...  We then provide the first hands-on tutorial for multi-objective optimisation of metabolic models in R.  ...  set of metabolic tasks to be included in the model [106] . tINIT prevents simultaneous flux in reversible reactions and allows the user to decide whether net production of all metabolites should be considered  ... 
doi:10.1093/bib/bbx053 pmid:28575143 fatcat:wcoccaxi5fhjjju7pimdx4w2oe

Untangling the web of functional and physical interactions in yeast

Markus J Herrgård, Bernhard Ø Palsson
2005 Journal of Biology  
An analysis of an integrated network of over 150,000 functional and physical interactions in yeast suggests that the network can be hierarchically decomposed into themes and thematic maps.  ...  This decomposition can be used to explore the organizational principles of integrated biological networks within cells.  ...  Within-pathway models refer to cases where genetic interactions occur between genes whose gene products participate in the same pathway or complex, whereas between-pathway models refer to cases where genetic  ... 
doi:10.1186/jbiol26 pmid:15982410 pmcid:PMC1175998 fatcat:zvfdlkspdfao5h6mwcx37h2a7a

GENOME-BASED MODELING AND DESIGN OF METABOLIC INTERACTIONS IN MICROBIAL COMMUNITIES

Radhakrishnan Mahadevan, Michael A. Henson
2012 Computational and Structural Biotechnology Journal  
co-operative interactions in E. coli, S. cerevisiae and other organisms for which well curated, genome-scale metabolic models and genetic engineering tools are available.  ...  Static Genome-scale Models of Microbial Communities Microbial communities often involve species interactions where a metabolic by-product of one species is the substrate for other species and vice versa  ... 
doi:10.5936/csbj.201210008 pmid:24688668 pmcid:PMC3962185 fatcat:vrgo5rz35rdu3k4q5f7kqdd5tq

Wine Science in the Omics Era: The Impact of Systems Biology on the Future of Wine Research

D. Rossouw Rossouw, F.F. Bauer
2016 South African Journal of Enology and Viticulture  
Furthermore, as most parameters are outside of individual control, predictability and consistency of the end product remain difficult to achieve.  ...  Indeed, the complexity of the process has prevented a deeper understanding of such interactions and causal relationships.  ...  In particular, the combination of comparative microarray datasets with existing models of yeast metabolism and interaction networks offers the potential for in silico evaluation of biologically relevant  ... 
doi:10.21548/30-2-1429 fatcat:xucxa265a5genciw2ycvjtok3i
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