BMC Systems Biology - Latest articles via MedWorm.com MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'BMC Systems Biology - Latest articles' source. Sun, 21 Mar 2010 17:04:04 +0100 Genotype networks in metabolic reaction spaces http://www.medworm.com/index.php?rid=3382233&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F4%2F30 Conclusions: Our work shows that phenotype-preserving genotype networks have generic organizational properties and that these properties are insensitive to the number of reactions in metabolic genotypes. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3382233 Fri, 19 Mar 2010 00:00:00 +0100 3382233 Zooming of states and parameters using a lumping approach including back-translation http://www.medworm.com/index.php?rid=3382234&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F4%2F28 Conclusions: Our novel lumping methodology allows for both automatic reduction of states using lumping, and for analytical retrieval of the original states and parameters without performing a new simulation. The two models can thus be considered as two degrees of zooming of the same model. This is a conceptually new development of model reduction approaches, which we think will stimulate much further research and will prove to be very useful in future modelling projects. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3382234 Thu, 18 Mar 2010 00:00:00 +0100 3382234 The internal state of medium spiny neurons varies in response to different input signals http://www.medworm.com/index.php?rid=3377749&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F4%2F26 Conclusions: Our study investigated the effects of various patterns of neurotransmission on signal integration and interpretation by DARPP-32 and showed that the DARPP-32 system has discernibility of many neurotransmission scenarios. We also screened out potential mechanisms underlying this capability of the DARPP-32 system. This type of insight deepens our understanding of neuronal signal transduction in normal medium spiny neurons, sheds light on neurological disorders associated with the striatum, and might aid the search for intervention targets in neurological diseases and drug addiction. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3377749 Wed, 17 Mar 2010 00:00:00 +0100 3377749 Meredys, a multi-compartment reaction-diffusion simulator using multistate realistic molecular complexes http://www.medworm.com/index.php?rid=3369764&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F4%2F24 Conclusions: Meredys provides a powerful and versatile way to run accurate simulations of molecular and sub-cellular systems, that complement existing multi-agent simulation systems. Meredys is a Free Software and the source code is available at http://meredys.sourceforge.net/. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3369764 Tue, 16 Mar 2010 00:00:00 +0100 3369764 Brownian diffusion of AMPA receptors is sufficient to explain fast onset of LTP http://www.medworm.com/index.php?rid=3369763&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F4%2F25 Conclusions: Fast accumulation of AMPA Receptors is consistent with experimentally observed fast onset of LTP expression. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3369763 Tue, 16 Mar 2010 00:00:00 +0100 3369763 Two additive mechanisms impair the differentiation of 'substrate-selective' p38 inhibitors from classical p38 inhibitors in vitro http://www.medworm.com/index.php?rid=3365738&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F4%2F23 Conclusions: Our integrated mechanistic modeling and experimental validation provides an example of how systems biology approaches can be applied to drug discovery and provide a basis for decision-making with limited chemical matter. We find that, given our current understanding, it is unlikely that 'substrate-selective' inhibitors of p38 will work as originally intended when placed in the context of more complex cellular environments, largely due to a stoichiometric excess of MK2 relative to p38. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3365738 Mon, 15 Mar 2010 00:00:00 +0100 3365738 Reverse engineering a gene network using an asynchronous parallel evolution strategy http://www.medworm.com/index.php?rid=3321741&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F4%2F17 Conclusions: Our results demonstrate that the piES is consistently faster and more reliable than the pLSA algorithm on this problem, and scales better with increasing numbers of nodes. In addition, the piES is especially well suited to further improvements and adaptations: Firstly, the algorithm's fast initial descent speed and high reliability make it a good candidate for being used as part of a global/local search hybrid algorithm. Secondly, it has the potential to be used as part of a hierarchical evolutionary algorithm, which takes advantage of modern multi-core computing architectures. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3321741 Tue, 02 Mar 2010 00:00:00 +0100 3321741 Inferring genetic interactions via a nonlinear model and an optimization algorithm http://www.medworm.com/index.php?rid=3310952&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F4%2F16 Conclusions: GASA is shown to infer both genetic interactions and transcriptional regulatory interactions well. In particular, GASA seems able to characterize the nonlinear mechanism of transcriptional regulatory interactions (TIs) in yeast, and may be applied to infer TIs in other organisms. The predicted genetic interactions of a subnetwork of human T-cell apoptosis coincide with existing partial pathways, suggesting the potential of GASA on inferring biochemical pathways. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3310952 Fri, 26 Feb 2010 00:00:00 +0100 3310952 Systems genetics analyses predict a transcription role for P2P-R: molecular confirmation that P2P-R is a transcriptional co-repressor http://www.medworm.com/index.php?rid=3306188&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F4%2F14 Conclusions: The findings presented in this study provide strong support for the value of systems genetics, especially GeneNetwork, in discovering new functions of genes that can be confirmed by molecular analysis. More specifically, these data provide evidence that the expression of P2P-R co-varies in a genetically-defined manner with large transcription networks and that P2P-R can function as a co-repressor of estrogen-dependent transcription. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3306188 Thu, 25 Feb 2010 00:00:00 +0100 3306188 Dynamical modeling of microRNA action on the protein translation process http://www.medworm.com/index.php?rid=3301574&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F4%2F13 Conclusions: Our analysis of the transient protein translation dynamics shows that it gives enough information to verify or reject a hypothesis about a particular molecular mechanism of microRNA action on protein translation. For multiscale systems only that action of microRNA is distinguishable which affects the parameters of dominant system (critical parameters), or changes the dominant system itself. Dominant systems generalize and further develop the old and very popular idea of limiting step. Algorithms for identifying dominant systems in multiscale kinetic models are straightforward but not trivial and depend only on the ordering of the model parameters but not on their concrete values. Asymptotic approach to kinetic models allows to put in order diverse experimental observations in ... BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3301574 Wed, 24 Feb 2010 00:00:00 +0100 3301574 A Novel microRNA and transcription factor mediated regulatory network in schizophrenia http://www.medworm.com/index.php?rid=3275412&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F4%2F10 Conclusions: This study provides many insights on the regulatory mechanisms of genes involved in schizophrenia. It represents the first investigation of a miRNA-TF regulatory network for a complex disease, as demonstrated in schizophrenia. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3275412 Mon, 15 Feb 2010 00:00:00 +0100 3275412 Diffusion is capable of translating anisotropic apoptosis initiation into a homogeneous execution of cell death http://www.medworm.com/index.php?rid=3238985&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F4%2F9 Conclusions: Multi-protein diffusion efficiently contributes to eliminating spatial asynchronies which are present during the initiation of apoptosis execution and thereby ensures homogeneous apoptosis execution throughout the entire cell body. For previously reported biological scenarios in which effector caspase activity was shown to be targeted selectively to specific subcellular regions additional mechanisms must exist that limit or spatially coordinate caspase activation and/or protect diffusing soluble caspase substrates from unwanted proteolysis. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3238985 Thu, 04 Feb 2010 00:00:00 +0100 3238985 In silico feasibility of novel biodegradation pathways for 1,2,4-trichlorobenzene http://www.medworm.com/index.php?rid=3235295&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F4%2F7 Conclusions: This work was aimed at understanding how novel biodegradation pathways influence the existing metabolism of a host organism. We have identified attractive targets for metabolic engineers interested in constructing a microorganism that can be used for bioremediation. Through this work, computational tools are shown to be useful in the design and evaluation of novel xenobiotic biodegradation pathways, identifying cellularly feasible degradation routes. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3235295 Tue, 02 Feb 2010 00:00:00 +0100 3235295 A general co-expression network-based approach to gene expression analysis: comparison and applications http://www.medworm.com/index.php?rid=3235294&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F4%2F8 Conclusions: We demonstrated that our novel approach is very effective in discovering the modular structures in microarray data, both for genes and for samples. As the method is essentially parameter-free, it may be applied to large data sets where the number of clusters is difficult to estimate. The method is also very general and can be applied to other types of data. A MATLAB implementation of our algorithm can be downloaded from http://cs.utsa.edu/~jruan/Software.html. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3235294 Tue, 02 Feb 2010 00:00:00 +0100 3235294 Blood flow controls coagulation onset via the positive feedback of factor VII activation by factor Xa http://www.medworm.com/index.php?rid=3211776&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F4%2F5 Conclusions: This mechanism explains difference between red and white thrombi observed in vivo at different shear rates. It can be speculated that this is a special switch protecting vascular system from uncontrolled formation and spreading of active coagulation factors in vessels with rapidly flowing blood. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3211776 Tue, 26 Jan 2010 00:00:00 +0100 3211776 Deciphering chemotaxis pathways using cross species comparisons http://www.medworm.com/index.php?rid=3163274&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F4%2F3 Conclusions: We find that many bacterial species potentially have multiple chemotaxis pathways, with grouping of che genes into operons likely to be a major factor in keeping signalling pathways distinct. Gene order is highly conserved with cheA-cheW and cheR-cheB blocks, perhaps reflecting functional linkage. CheY behaves differently to other Che proteins, both in its genomic location and its putative protein interactions, which should be considered when modelling chemotaxis pathways. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3163274 Mon, 11 Jan 2010 00:00:00 +0100 3163274 Snazer: the simulations and networks analyzer http://www.medworm.com/index.php?rid=3148601&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F4%2F1 Conclusions: Snazer is a solid prototype that integrates biological network and simulation time-course data analysis techniques. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3148601 Thu, 07 Jan 2010 00:00:00 +0100 3148601 A computational approach to resolve cell level contributions to early glandular epithelial cancer progression http://www.medworm.com/index.php?rid=3135238&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F122 Conclusions: ISEA mechanisms, behaviors, and phenotype may have biological counterparts. To the extent that in silico-to-in vitro mappings are valid, the results suggest plausible, additional mechanisms of in vitro cancer reconstruction or reversion, and raise potentially significant implications for early cancer diagnosis based on histology. Further ISEA development and use is expected to provide a viable platform to complement in vitro methods for unraveling the mechanistic basis of epithelial morphogenesis and cancer progression. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3135238 Thu, 31 Dec 2009 00:00:00 +0100 3135238 Ranges of control in the transcriptional regulation of Escherichia coli http://www.medworm.com/index.php?rid=3118415&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F119 Conclusions: These findings support previous evidence from gene expression patterns for two distinct logical types of control, namely digital control (i.e. network-based control mediated by dedicated transcription factors) and analog control (i.e. control based on genome structure and mediated by neighborhood on the genome). (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3118415 Thu, 24 Dec 2009 00:00:00 +0100 3118415 Computational modeling of the EGFR network elucidates control mechanisms regulating signal dynamics http://www.medworm.com/index.php?rid=3114543&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F118 Conclusions: The insights gained from simulating this executable model facilitate the formulation of specific hypotheses regarding the control mechanisms of the EGFR signaling, and further substantiate the benefit to construct abstract executable models of large complex biological networks. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3114543 Tue, 22 Dec 2009 00:00:00 +0100 3114543 Human synthetic lethal inference as potential anti-cancer target gene detection http://www.medworm.com/index.php?rid=3092284&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F116 Conclusions: Our work provides a complementary alternative to the current methods for drug discovering and gene target identification in anti-cancer research. Novel SL screening analysis and the use of highly curated databases would contribute to improve the results of this methodology. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3092284 Wed, 16 Dec 2009 00:00:00 +0100 3092284 Detecting coordinated regulation of multi-protein complexes using logic analysis of gene expression http://www.medworm.com/index.php?rid=3088733&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F115 Conclusions: The analysis proposed here focuses on relationships among triplets of genes that are not evident when genes are examined in a pairwise fashion as in typical clustering methods. By grouping gene triplets, we are able to decipher coordinated regulation among sets of three complexes. Moreover, using all triplets that involve coordinated regulation with the ribosome, we derive a large network involving this essential cellular complex. In this network we find that all multi-protein complexes that belong to the same functional class are regulated in the same direction as a group (either induced or repressed). (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3088733 Mon, 14 Dec 2009 00:00:00 +0100 3088733 In silico approaches to study mass and energy flows in microbial consortia: a syntrophic case study http://www.medworm.com/index.php?rid=3074880&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F114 Conclusion: The three modeling approaches represent a flexible toolbox for creating cellular metabolic networks to study microbial communities on scales ranging from cells to ecosystems. A comparison of the three methods highlights considerations for selecting the one most appropriate for a given microbial system. For instance, communities represented only by metagenomic data can be modeled using the pooled method which analyzes a community's total metabolic potential without attempting to partition enzymes to different organisms. Systems with extensive a priori information on microbial guilds can be represented using the compartmentalized technique, employing distinct control volumes to separate guild-appropriate enzymes and metabolites. If the complexity of a compartmentalized network cr... BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3074880 Thu, 10 Dec 2009 00:00:00 +0100 3074880 Impact of environmental inputs on reverse-engineering approach to network structures http://www.medworm.com/index.php?rid=3056029&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F113 Conclusions: We demonstrate that environment inputs are crucial for correctly inferring network structures. Harmonic causal method is proved to be a powerful technique to detect environment inputs and uncover network structures, especially when the biological data exhibit periodic oscillations. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3056029 Fri, 04 Dec 2009 00:00:00 +0100 3056029 Inferring a transcriptional regulatory network of the cytokinesis-related genes by network component analysis http://www.medworm.com/index.php?rid=3033336&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F110 Conclusion: In this study, using S. cerevisiae as a model system, NCA was successfully applied to infer similar regulatory actions of transcription factor activities from two various microarray databases and several partial transcription factor-gene connectivity datasets for selected cytokinesis-related genes independent of data sizes. The regulated action for four selected cytokinesis-related genes (BUD4, CHS2, IQG1, and CDC5) belongs to the M-phase or M/G1 phase, consistent with the empirical observations that in S. cerevisiae, the Mcm1-Ndd1-Fkh2 transcription factor complex can regulate expression of the cytokinesis-related genes BUD4, CHS2, IQG1, and CDC5. Since Bud4, Iqg1, and Cdc5 are highly conserved between human and yeast, results obtained from NCA for cytokinesis in the budding y... BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=3033336 Fri, 27 Nov 2009 00:00:00 +0100 3033336 DASMiner: discovering and integrating data from DAS sources http://www.medworm.com/index.php?rid=2999043&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F109 Conclusions: The support of the DAS protocol allows that hundreds of molecular biology databases to be treated as a federated, online collection of resources. DASMiner enables full exploration of these resources, and can be used to deploy applications and create integrated views of biological systems using the information deposited in DAS repositories. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2999043 Tue, 17 Nov 2009 00:00:00 +0100 2999043 Network analysis of the transcriptional pattern of young and old cells of Escherichia coli during lag phase http://www.medworm.com/index.php?rid=2995304&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F108 Conclusion: Network analysis revealed very different transcriptional activities during the lag period in old and young cells. Rejuvenation seems to take place during exponential growth by replicative dilution of old cellular components. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2995304 Mon, 16 Nov 2009 00:00:00 +0100 2995304 Long-term prediction of fish growth under varying ambient temperatures using a multiscale dynamic model http://www.medworm.com/index.php?rid=2980619&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F107 Conclusions: We demonstrate that, despite thedifficulties involved, multiscale models in biology can yieldreasonable and useful results. The model predictions are reliableover several timescales and in the presence of strong temperaturefluctuations, which are crucial factors for modeling marine organismgrowth. The model provides important improvements over existingmodels. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2980619 Tue, 10 Nov 2009 00:00:00 +0100 2980619 Using the ratio of means as the effect size measure in combining results of microarray experiments http://www.medworm.com/index.php?rid=2966623&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F106 Conclusions: Our results show that the proposed effect size measure (log ratio of means) has better power to identify differentially expressed genes, and that the detected genes have better performance in predicting cancer outcomes than the commonly used effect size measure, the standardized mean difference (SMD), under both quality-weighted and quality-unweighted data integration frameworks. The new effect size measure and the quality-weighted microarray data integration framework provide efficient ways to combine microarray results. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2966623 Thu, 05 Nov 2009 00:00:00 +0100 2966623 Inferring branching pathways in genome-scale metabolic networks http://www.medworm.com/index.php?rid=2943122&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F103 Conclusions: ReTrace is a useful method in metabolic path finding tasks, combining some of the best aspects in constraint-based and graph-theoretic methods. It finds use in a multitude of tasks ranging from metabolic engineering to metabolic reconstruction of recently sequenced organisms. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2943122 Thu, 29 Oct 2009 00:00:00 +0100 2943122 13C-metabolic flux ratio and novel carbon path analyses confirmed that Trichoderma reesei uses primarily the respirative pathway also on the preferred carbon source glucose http://www.medworm.com/index.php?rid=2943121&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F104 Conclusions: High similarity between the biosynthetic pathways of amino acids in T. reesei and yeast S. cerevisiae was concluded. In vivo flux distributions confirmed that T. reesei uses primarily the respirative pathway also when growing on the repressive carbon source glucose in contrast to Saccharomyces cerevisiae, which substantially diminishes the respirative pathway flux under glucose repression. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2943121 Thu, 29 Oct 2009 00:00:00 +0100 2943121 How to identify essential genes from molecular networks? http://www.medworm.com/index.php?rid=2885922&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F102 Conclusions: The method reported here describes a reliable procedure to predict essential genes from molecular networks. Our results show that essential genes may be predicted only by combining centrality measures, revealing the complex nature of the function of essential genes. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2885922 Mon, 12 Oct 2009 23:00:00 +0100 2885922 Investigating the robustness of the classical enzyme kinetic equations in small intracellular compartments http://www.medworm.com/index.php?rid=2875218&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F101 Conclusions: The derived mesoscopic rate equations describe subcellular enzyme reaction kinetics, taking into account, for the first time, the simultaneous influence of both intrinsic noise and the mode of transport. They clearly show the range of applicability of the conventional deterministic equation models, namely intracellular conditions compatible with diffusive transport and simple enzyme mechanisms in several hundred nanometre-sized compartments. An active transport mechanism coupled with large intrinsic noise in enzyme concentrations is shown to lead to huge deviations from the predictions of deterministic models. This has implications for the common approach of modeling large intracellular reaction networks using ordinary differential equations and also for the calculation of the... BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2875218 Wed, 07 Oct 2009 23:00:00 +0100 2875218 Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway http://www.medworm.com/index.php?rid=2861965&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F100 Conclusions: Our results suggest that different routes to ERK activation are being utilised in different cancerous situations which therefore has interesting implications for drug selection strategies. We also conducted a comparison of the critical differences between signalling from different growth factor receptors (namely EGFR, mutated EGFR, NGF, and Insulin) with our results suggesting the difference between the systems are large scale and can be attributed to the presence/absence of entire pathways rather than subtle difference in individual rate constants between the systems. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2861965 Sun, 04 Oct 2009 23:00:00 +0100 2861965 Modeling system states in liver cells: Survival, apoptosis and their modifications in response to viral infection http://www.medworm.com/index.php?rid=2819063&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F97 Conclusions: A network model for apoptosis and crosstalk in hepatocytes shows four different system states and reproduces a number of different conditions around apoptosis including effects of different growth substrates and viral infections. It produces semi-quantitative predictions on the activity of individual nodes, agreeing with experimental data. The model (SBML format) and all data are available for further predictions and development (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2819063 Mon, 21 Sep 2009 23:00:00 +0100 2819063 A method for determining the robustness of bio-molecular oscillator models http://www.medworm.com/index.php?rid=2879125&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F95 Conclusion: The method here proposed for quantifying the robustness of biochemical oscillator models is computationally less demanding than similar multiparamter variation techniques available in the literature. It also provides tighter bounds on two models previously analyzed in the literature. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2879125 Sun, 20 Sep 2009 23:00:00 +0100 2879125 Inferring Drosophila gap gene regulatory network: a parameter sensitivity and perturbation analysis http://www.medworm.com/index.php?rid=2814208&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F94 Conclusions: Parameter sensitivity analysis allows one to discriminate between circuits having significant parameter and qualitative differences but exhibiting the same quantitative pattern. Furthermore, we show that using a stochastic model derived from a deterministic solution, one can introduce fluctuations within the model to analyze the circuits' robustness. Ultimately, we show that there is a close relation between circuit sensitivity and robustness to fluctuation, and that circuit robustness is rather modular than global. The current study shows that reverse engineering of GRNs should not only focus on estimating parameters by minimizing the difference between observation and simulation but also on other model properties. Our study suggests that multi-objective optimization based on... BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2814208 Sun, 20 Sep 2009 23:00:00 +0100 2814208 A Method for determining the dobustness of bio-molecular oscillator models http://www.medworm.com/index.php?rid=2814207&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F95 Conclusions: The method here proposed for quantifying the robustness of biochemical oscillator models is computationally less demanding than similar multiparamter variation techniques available in the literature. It also provides tighter bounds on two models previously analyzed in the literature. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2814207 Sun, 20 Sep 2009 23:00:00 +0100 2814207 A systems biology framework for modeling metabolic enzyme inhibition of Mycobacterium tuberculosis http://www.medworm.com/index.php?rid=2799948&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F92 Conclusions: The predicted results quantitatively reproduced the experimentally measured dose-response curves, ranging over three orders of magnitude in inhibitor concentration. Thus, by allowing for detailed specifications of the underlying enzymatic kinetics, metabolic reactions/constraints, and growth media, our model captured the essential chemical and biological factors that determine the effects of drug inhibition on in vitro growth of M. tuberculosis cells. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2799948 Mon, 14 Sep 2009 23:00:00 +0100 2799948 Metabolism as means for hypoxia adaptation: metabolic profiling and flux balance analysis http://www.medworm.com/index.php?rid=2781449&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F91 Conclusions: We suggest a network-level hypothesis of metabolic regulation in hypoxia-adapted flies, in which lower baseline rates of biosynthesis in adapted flies draws less anaplerotic flux, resulting in lower rates of glycolysis, less acidosis, and more efficient use of substrate during acute hypoxic stress. In addition we suggest new specific hypothesis, which were found to be consistent with existing data. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2781449 Tue, 08 Sep 2009 23:00:00 +0100 2781449 The smallest chemical reaction system with bistability http://www.medworm.com/index.php?rid=2774351&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F90 Conclusions: The presented minimal bistable system finally clarifies the often discussed question for the necessary conditions for bistability. The three necessary conditions are: positive feedback, a mechanism to filter out small stimuli and a mechanism to prevent explosions. This is important for modelling bistability with simple systems and for synthetically designing new bistable systems. Our simple model system is also well suited for corresponding teaching purposes. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2774351 Mon, 07 Sep 2009 23:00:00 +0100 2774351 Hybrid stochastic simplifications for multiscale gene networks http://www.medworm.com/index.php?rid=2772074&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F89 Conclusions: Hybrid simplifications can be used for onion-like (multilayered) approaches to multi-scale biochemical systems, in which various descriptions are used at various scales. Sets of discrete and continuous variables are treated with different methods and are coupled together in a physically justified approach. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2772074 Sun, 06 Sep 2009 23:00:00 +0100 2772074 The genotype-phenotype relationship in multicellular pattern-generating models - the neglected role of pattern descriptors http://www.medworm.com/index.php?rid=2765445&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F87 Conclusions: The results suggest that our approach may qualify as a general procedure for how to relate relevant features and characteristics of emergent patterns to the functional relationships, parameter values and initial values of an underlying pattern-generating mathematical model. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2765445 Thu, 03 Sep 2009 23:00:00 +0100 2765445 The crosstalk between EGF, IGF, and Insulin cell signaling pathways - computational and experimental analysis http://www.medworm.com/index.php?rid=2765444&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F88 Conclusions: The simple model implemented in this paper provides a valuable first step in modeling signaling networks. However, to obtain a fully predictive model, a more detailed knowledge regarding parameters of individual interactions might be necessary. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2765444 Thu, 03 Sep 2009 23:00:00 +0100 2765444 Monte-Carlo analysis of an ODE Model of the Sea Urchin Endomesoderm Network http://www.medworm.com/index.php?rid=2726865&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F83 Conclusions: The method described in this paper enables an evaluation of network topologies of GRNs withoutrequiring any parameter values. The benefit of this method is exemplified in the first mathematical analysis ofthe complete Endomesoderm Network Model. The predictions we provide deliver candidate nodes in the networkthat are likely to be erroneous or miss unknown connections, which may need additional experiments to improvethe network topology. This mathematical model can serve as a scaffold for detailed and more realistic models.We propose that our method can be used to assess a completeness grade of any GRN. This could be especiallyuseful for GRNs involved in human diseases, where often the amount of connectivity is unknown and/or manygenes/interactions are missing. (Source: BMC Sy... BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2726865 Sat, 22 Aug 2009 23:00:00 +0100 2726865 Visualizing Post Genomics Data-sets on customized Pathway Maps by ProMeTra - aeration-dependent gene expression and metabolism of Corynebacterium glutamicum as an example. http://www.medworm.com/index.php?rid=2724222&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F82 Conclusions: We demonstrate the functionality of ProMeTra with quantitative metabolomics and trasncriptomics data obtained from a fermentation experiment of the L-lysine producing strain Corynebacterium glutamicum DM1730. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2724222 Sat, 22 Aug 2009 23:00:00 +0100 2724222 Optimal drug combinations and minimal hitting sets http://www.medworm.com/index.php?rid=2678248&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F81 Conclusions: The drug-response graph and the associated minimal hitting set method can be use to uncover effective drug combinations in anticancer drug screens and drug development programs targeting heterogeneous populations of infectious agents such as HIV. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2678248 Wed, 05 Aug 2009 23:00:00 +0100 2678248 Knowledge based identification of essential signaling from genome-scale siRNA experiments http://www.medworm.com/index.php?rid=2670432&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F80 Conclusion: PIPA provides an analytical framework to interpret siRNA screen data by merging biologically annotated gene sets with the human interactome. As a result we identify pathways and signaling hypotheses that are statistically enriched to effect cell growth in human cell lines. This method provides a complementary approach to standard gene set enrichment that utilizes the additional knowledge of specific interactions within biological gene sets. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2670432 Tue, 04 Aug 2009 23:00:00 +0100 2670432 A possibilistic framework for constraint-based metabolic flux analysis http://www.medworm.com/index.php?rid=2657045&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F79 Conclusions: We introduce a possibilistic framework for the estimation of metabolic fluxes, which is shown to be flexible, reliable, usable in scenarios lacking data and computationally efficient. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2657045 Thu, 30 Jul 2009 23:00:00 +0100 2657045 A dynamic network of transcription in LPS-treated human subjects http://www.medworm.com/index.php?rid=2648587&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F78 Conclusions: Using NCA, we were able to build a network that accounted for between 8-11% genes in the known transcriptional response to LPS in humans. The dynamic network illustrated changes of transcription factor activities and gene expressions as well as interactions of signaling proteins, transcription factors and target genes. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2648587 Mon, 27 Jul 2009 23:00:00 +0100 2648587 Adapted Boolean network models for extracellular matrix formation http://www.medworm.com/index.php?rid=2625355&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F77 Conclusion: The newly developed method successfully and iteratively integrated expert knowledge at different steps, resulting in a promising solution for the in-depth understanding of regulatory pathways in disease dynamics. The knowledge base containing all the temporal rules may be queried to predict the functional consequences of observed or hypothetical gene expression disturbances. Furthermore, new hypotheses about gene relations were derived which await further experimental validation. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2625355 Mon, 20 Jul 2009 23:00:00 +0100 2625355 Hierarchical coordination of periodic genes in the cell cycle of Saccharomyces cerevisiae http://www.medworm.com/index.php?rid=2620584&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F76 Conclusions: Aside from the results obtained for the cell cycle of yeast our approach could be exemplary for the analysis of general pathways by exploiting the rich causal structure of inferred and/or curated gene networks including protein or signaling networks. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2620584 Sun, 19 Jul 2009 23:00:00 +0100 2620584 An Integrative ChIP-chip and Gene Expression Profiling to Model SMAD Regulatory Modules http://www.medworm.com/index.php?rid=2613444&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F73 Conclusion: Together, the computational results further the understanding of the interactions between SMAD and other transcription factors at specific target promoters, and provide the basis for more targeted experimental verification of the co-regulatory modules. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2613444 Thu, 16 Jul 2009 23:00:00 +0100 2613444 Cascading signaling pathways improve the fidelity of a stochastically and deterministically simulated molecular RS latch http://www.medworm.com/index.php?rid=2610427&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F72 Conclusion: Thus, the common biological theme of cascading signaling pathways is advantageous for maintaining the fidelity of a memory latch in the presence of crosstalk. The experimental implementation of such a latch system will lead to novel approaches to cell control using synthetic proteins and contribute to our understanding of why cells behave differently even when given the same stimulus. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2610427 Thu, 16 Jul 2009 23:00:00 +0100 2610427 Mechanism of PP2A-mediated IKKbeta dephosphorylation: a systems biological approach http://www.medworm.com/index.php?rid=2610428&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F71 Conclusions: The model developed here can be used as a reliable building block of larger NFkappaB models and offers comprehensive simplification potential for future modeling of NFkappaB signaling. It gives more insight into the newly discovered mechanisms for IKK deactivation and allows for substantiated predictions and investigation of different hypotheses.The evidence of constitutive activity of PP2Ac at the IKK complex provides new insights into the feedback regulation of NFkappaB, which is crucial for the development of new anti-cancer strategies. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2610428 Wed, 15 Jul 2009 23:00:00 +0100 2610428 Deterministic mathematical models of the cAMP Pathway in Saccharomyces cerevisiae http://www.medworm.com/index.php?rid=2605444&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F70 Conclusions: We suggest that the lower number of reactions and parameters makes these models suitable for integrating them with models of metabolism or of the cell cycle in S. cerevisiae. Similar models could be also useful for studies in the human pathogen Candida albicans as well as other less well-characterized fungal species. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2605444 Wed, 15 Jul 2009 23:00:00 +0100 2605444 Interactome and Gene Ontology provide congruent yet subtly different views of a eukaryotic cell http://www.medworm.com/index.php?rid=2605445&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F69 Conclusions: The structures of the yeast cell deduced from GO and interactome are substantially congruent. However, some significant differences were also detected, which may contribute to a better understanding of cell function and also to a refinement of the current ontologies. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2605445 Tue, 14 Jul 2009 23:00:00 +0100 2605445 Computing phenomenologic Adair-Klotz constants from microscopic MWC parameters http://www.medworm.com/index.php?rid=2601347&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F68 Conclusions: The validation of computational models requires methods to relate model parameters to experimentally observable quantities. We provide such a method for comparing generalised MWC allosteric models to experimentally determined Adair-Klotz constants. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2601347 Mon, 13 Jul 2009 23:00:00 +0100 2601347 A systematic design method for robust synthetic biology to satisfy design specifications http://www.medworm.com/index.php?rid=2560181&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F66 Conclusions: Based on four design specifications, a systematic design procedure is developed for designers to engineer a robust synthetic biology network that can achieve its desired steady state behavior under parameter fluctuations, external disturbances and functional variations in the host cell. Therefore, the proposed systematic design method has good potential for the robust synthetic gene network design. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2560181 Mon, 29 Jun 2009 23:00:00 +0100 2560181 BowTieBuilder: modeling signal transduction pathways http://www.medworm.com/index.php?rid=2560180&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F67 Conclusions: We show that BowTieBuilder, given multiple source and/or target proteins, infers pathways with satisfactory recall and precision rates and detects the core proteins of each pathway. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2560180 Mon, 29 Jun 2009 23:00:00 +0100 2560180 Clustered microRNAs' coordination in regulating protein-protein interaction network http://www.medworm.com/index.php?rid=2521903&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F65 Conclusions: In summary, this work supports the hypothesis of intra-cluster coordination and investigates the extent of this coordination. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2521903 Thu, 25 Jun 2009 23:00:00 +0100 2521903 Stochastic simulation and analysis of biomolecular reaction networks http://www.medworm.com/index.php?rid=2504211&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F64 Conclusions: The two main factors affecting the analysis of stochastic simulations are: (1) the selection of time intervals to compute or average state variables and (2) the number of simulations generated to evaluate the system behavior. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2504211 Tue, 16 Jun 2009 23:00:00 +0100 2504211 Serial evolutionary networks of within-patient HIV-1 sequences reveal patterns of evolution of X4 strains http://www.medworm.com/index.php?rid=2504213&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F62 Conclusions: Our results indicate that serial evolutionary networks of HIV sequences enable systematic statistical analysis of the implicit relations embedded in the topology of the structure and can greatly facilitate identification of patterns of evolution that can lead to specific hypotheses and new insights. The conclusions of applying our method to empirical HIV data support the conventional wisdom of the new generation HIV treatments, that in order to keep the virus in check, viral loads need to be suppressed to almost undetectable levels (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2504213 Mon, 15 Jun 2009 23:00:00 +0100 2504213 The Symbiosis Interactome: a computational approach reveals novel components, functional interactions and modules in Sinorhizobium meliloti http://www.medworm.com/index.php?rid=2504212&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F63 Conclusions: Our 'systems-based model' represents a novel framework for studying host-microbe interactions, provides a theoretical basis for further experimental validations, and can also be applied to the study of other complex processes such as diseases. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2504212 Mon, 15 Jun 2009 23:00:00 +0100 2504212 Intervention in gene regulatory networks via greedy control policies based on long-run behavior http://www.medworm.com/index.php?rid=2504214&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F61 Conclusions: The newly proposed control policies have better performance in general than the MFPT policy and, as indicated by the results on the mammalian cell cycle network, they can potentially serve as future gene therapeutic intervention strategies. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2504214 Sun, 14 Jun 2009 23:00:00 +0100 2504214 The mathematics of tanning http://www.medworm.com/index.php?rid=2468043&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F60 Conclusions: Despite the paucity of experimental validation data the model is constrained enough to serve as a foundation for the establishment of a theoretical-experimental research programme aimed at elucidating the more fine-grained regulatory anatomy underlying the tanning response. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2468043 Tue, 09 Jun 2009 04:00:00 +0100 2468043 ChemChains: a platform for simulation and analysis of biochemical networks aimed to laboratory scientists http://www.medworm.com/index.php?rid=2462759&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F58 Conclusions: ChemChains combines the advantages of logical and continuous modeling and provides a way for laboratory biologists to perform in silico experiments on mathematical models easily, a necessary component of laboratory research in the systems biology era. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2462759 Sat, 06 Jun 2009 04:00:00 +0100 2462759 A system biology approach highlights a hormonal enhancer effect on regulation of genes in a nitrate responsive "biomodule" http://www.medworm.com/index.php?rid=2462758&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F59 Conclusion: This systems analysis enabled us to derive a hypothesis in which hormone signals are proposed to enhance the nitrate response, providing a potential mechanistic explanation for the link between nitrate signaling and the control of plant development. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2462758 Sat, 06 Jun 2009 04:00:00 +0100 2462758 LeishCyc: a biochemical pathways database for Leishmania major http://www.medworm.com/index.php?rid=2456079&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F57 Conclusions: The LeishCyc database describes Leishmania major genes, gene products, metabolites, their relationships and biochemical organization into metabolic pathways. LeishCyc provides a systematic approach to organizing the evolving information about Leishmania biochemical networks and is a tool for analysis, interpretation, and visualization of Leishmania 'omics (transcriptomics, proteomics, metabolomics) data in the context of metabolic pathways. LeishCyc is the first such database for the Trypanosomatidae family, which includes a number of other important human parasites. Flexible query/visualization capabilities are provided by the Pathway Tools software and its Web interface. The LeishCyc database is made freely available on the Internet (www.leishcyc.org). (Source: BMC Systems B... BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2456079 Fri, 05 Jun 2009 04:00:00 +0100 2456079 Computational disease modeling - fact or fiction? http://www.medworm.com/index.php?rid=2456080&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F56 Conclusions: During the workshop it became obvious that diverse scientific modeling cultures (from computational neuroscience, theory, data-driven machine-learning approaches, agent-based modeling, network modeling and stochastic-molecular simulations) would benefit from intense cross-talk on shared theoretical issues in order to make progress on clinically relevant problems. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2456080 Thu, 04 Jun 2009 04:00:00 +0100 2456080 A graphical model approach for inferring large-scale networks integrating gene expression and genetic polymorphism http://www.medworm.com/index.php?rid=2439872&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F55 Conclusions: Our results suggest that graphical models based on integrative genomic data are computationally efficient, work well with small samples, and can describe complex interactions among genes and polymorphisms that could not be identified by pair-wise association testing. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2439872 Wed, 27 May 2009 04:00:00 +0100 2439872 Proteomic and network analysis characterize stage-specific metabolism in Trypanosoma cruzi http://www.medworm.com/index.php?rid=2422789&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F52 Conclusions: This work demonstrates the utility of constraint-based models for integrating various sources of data (e.g., genomics, primary biochemical literature, proteomics) to generate testable hypotheses. This model represents an approach for the systematic study of T. cruzi metabolism under a wide range of conditions and perturbations, and should eventually aid in the identification of urgently needed novel chemotherapeutic targets. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2422789 Sat, 16 May 2009 04:00:00 +0100 2422789 On the functional diversity of dynamical behaviour in genetic and metabolic feedback systems http://www.medworm.com/index.php?rid=2413377&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F51 Conclusion: The analytical methods and insights presented in this study demonstrate that reallocation of the feedback loop may or may not make the system more stable; the specific effect is determined by the degradation rates of the newly inhibited molecular species. As the loop moves closer to the end of the pathway, the minimum Hill coefficient for oscillation is reduced. Furthermore, under general (unequal) values of the degradation rates, system extension becomes more stable only when the added species degrades slower than it is being produced; otherwise the system is more prone to oscillation. The coupling of loops significantly increases the richness of dynamical bifurcation characteristics. The likelihood of having oscillatory behaviour is directly determined by the loops' strength:... BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2413377 Mon, 11 May 2009 04:00:00 +0100 2413377 miRNA-regulated dynamics in circadian oscillator models http://www.medworm.com/index.php?rid=2396831&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F45 Conclusion: miRNAs can have a profound effect on the dynamics of regulatory modules, both by control of amplitude, namely by affecting the level of gene expression, as well as by control or alteration of frequency, namely by interference with the temporal sequence of gene production or delivery. We believe that our results are valid for a variety of regulatory systems, beyond the exemplars discussed here. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2396831 Tue, 05 May 2009 04:00:00 +0100 2396831 Genetic and environmental pathways to complex diseases http://www.medworm.com/index.php?rid=2396830&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F46 Conclusions: Identification of key regulatory pathways that integrate genetic and environmental modulators define disease associated targets that will allow for efficient screening of large numbers of environmental factors, screening that could set priorities for further research and guide public health decisions. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2396830 Tue, 05 May 2009 04:00:00 +0100 2396830 Identification of neutral biochemical network models from time series data http://www.medworm.com/index.php?rid=2396829&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F47 Conclusions: The proposed parameter estimation methodology was applied to actual time series data from the glycolytic pathway of the bacterium Lactococcus lactis and led to ensembles of models with different network topologies. In parallel, the parameter optimization algorithm was applied to the same dynamical data upon imposing a pre-specified network topology derived from prior biological knowledge, and the results from both strategies were compared. The results suggest that the proposed method may serve as a powerful exploration tool for testing hypotheses and the design of new experiments. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2396829 Tue, 05 May 2009 04:00:00 +0100 2396829 Information flow during gene activation by signaling molecules: ethylene transduction in Arabidopsis cells as a study system http://www.medworm.com/index.php?rid=2396828&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F48 Conclusions: The ethylene signaling pathway cuts off very low and very high frequencies, allowing a window of frequency response in which the nucleus reads the incoming message as a sinusoidal input. Out of this window the nucleus reads the input message as an approximately non-varying one. From this frequency response analysis we estimate: a) the gain of the system during the synthesis of the protein ERF1 (~ -5.6 dB); b) the rate of information transfer (0.003 bits) during the transport of each new ERF1 molecule into the nucleus and c) the time of synthesis of each new ERF1 molecule (~ 21.3 s). Finally, we demonstrate that in the case of the system of a single master gene (ERF1) and a single slave gene (HLS1), the total Shannon entropy is completely determined by the uncertainty associate... BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2396828 Tue, 05 May 2009 04:00:00 +0100 2396828 Using In Silico Models to Simulate Dual Perturbation Experiments: Procedure Development and Interpretation of Outcomes http://www.medworm.com/index.php?rid=2380135&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F44 Conclusion: Dual perturbation experiments in silico are much more informative for the characterization of functional states than single perturbations. Predictions from an experimentally validated cellular model of metabolism indicate that the measurement of cofactor precursor transport rates can inform the internal state of the cell when the external demands are altered or a causal genetic variation is introduced. Finally, genetic mutations that alter the clinical phenotype may also disrupt the 'natural' time scale hierarchy of interactions in the network. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2380135 Thu, 30 Apr 2009 04:00:00 +0100 2380135 Simulation-based model checking approach to cell fate specification during Caenorhabditis elegans vulval development by hybrid functional Petri net with extension http://www.medworm.com/index.php?rid=2368506&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F42 Conclusions: The quantitative simulation-based model checking approach is a useful means to provide us valuable biological insights and better understandings of biological systems and observation data that may be hard to capture with the qualitative one. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2368506 Mon, 27 Apr 2009 04:00:00 +0100 2368506 Narrative-based computational modelling of the Gp130/JAK/STAT signalling pathway http://www.medworm.com/index.php?rid=2340238&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F40 Conclusions: The described narrative model of the gp130/JAK/STAT pathway represents an interesting case study showing how, by using this approach, researchers can model biological systems without explicitly dealing with formal notations and mathematical expressions (typically used for biochemical modelling), nevertheless being able to obtain simulation and analysis results. We present the model and the sensitivity analysis results we have obtained, that allow us to identify the parameters which are most sensitive to perturbations. The results, which are shown to be in agreement with existing mathematical models of the gp130/JAK/STAT pathway, serve us as a form of validation of the model and of the approach itself. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2340238 Wed, 15 Apr 2009 04:00:00 +0100 2340238 Reconstruction of Escherichia coli transcriptional regulatory networks via regulon-based associations http://www.medworm.com/index.php?rid=2340239&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F39 Conclusion: Information about transcriptional activity of documented co-regulated genes (a core regulon) should be sufficient for discovering new target genes whose transcriptional activities significantly co-vary with the activity of the core regulon members. Our ability to derive a highly significant consensus network by applying the regulon-based approach to two very different data sets demonstrated the efficiency of this strategy. We believe that this approach can be used to reconstruct gene regulatory networks of other organisms for which only sub-sets of known interactions are available. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2340239 Tue, 14 Apr 2009 04:00:00 +0100 2340239 Connecting extracellular metabolomic measurements to intracellular flux states in yeast http://www.medworm.com/index.php?rid=2295777&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F37 Conclusions: Our results indicate that integrating quantitative extracellular metabolomic profiles in a constraint-based framework enables inferring changes in intracellular metabolic flux states. Similar methods could potentially be applied towards analyzing biofluid metabolome variations related to human physiological and disease states. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2295777 Wed, 25 Mar 2009 04:00:00 +0100 2295777 Identifying disease-specific genes based on their topological significance in protein networks http://www.medworm.com/index.php?rid=2295780&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F36 Conclusions: The systematic and automated approach described in this paper is readily applicable to uncovering high-quality therapeutic targets, and holds great promise for developing network-based combinational treatment strategies for a wide range of diseases. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2295780 Mon, 23 Mar 2009 04:00:00 +0100 2295780 Information processing in the transcriptional regulatory network of yeast: Functional robustness http://www.medworm.com/index.php?rid=2283578&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F35 Conclusions: Our study does not only demonstrate that a combination of graph theoretical, information theoretical and statistical methods leads to meaningful biological results but also that such methods allow to study information processing in gene networks instead of just their structural properties. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2283578 Thu, 19 Mar 2009 04:00:00 +0100 2283578 Reconstruction of Metabolic Pathways for the Cattle Genome http://www.medworm.com/index.php?rid=2258336&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F33 Conclusions: CattleCyc is a powerful tool for understanding the biology of ruminants and other cetartiodactyl species. In addition, the approach used to develop CattleCyc provides a framework for the metabolic reconstruction of other newly sequenced mammalian genomes. It is clear that metabolic pathway analysis strongly reflects the quality of the underlying genome annotations. Thus, having well-annotated genomes from many mammalian species hosted in BioCyc will facilitate the comparative analysis of metabolic pathways among different species and a systems approach to comparative physiology. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2258336 Thu, 12 Mar 2009 04:00:00 +0100 2258336 Topological and organizational properties of the products of house-keeping and tissue-specific genes in protein-protein interaction networks http://www.medworm.com/index.php?rid=2258338&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F32 Conclusion: Our analysis showed that house-keeping gene-encoded proteins tend to occupy important network positions, while those encoded by tissue-specific genes do not. The biological implications of our findings were discussed and we proposed a hypothesis regarding how cells organize their protein tools in protein-protein interaction networks. Our results led us to speculate that house-keeping gene-encoded proteins might form a core in human protein-protein interaction networks, while clusters of tissue-specific gene-encoded proteins are attached to the core at more peripheral positions of the networks. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2258338 Wed, 11 Mar 2009 04:00:00 +0100 2258338 Small molecule activators of SIRT1 replicate signaling pathways triggered by calorie restriction in vivo http://www.medworm.com/index.php?rid=2258340&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F31 Conclusions: CNM of gene expression data from mice treated with SRT501 or SRT1720 in combination with supporting in vitro and in vivo data demonstrates that SRT501 and SRT1720 produce a signaling profile that mirrors CR, improves glucose and insulin homeostasis, and acts via SIRT1 activation in vivo. Taken together these results are encouraging regarding the use of small molecule activators of SIRT1 for therapeutic intervention into type 2 diabetes, a strategy which is currently being investigated in multiple clinical trials. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2258340 Tue, 10 Mar 2009 04:00:00 +0100 2258340 Decomposing complex reaction networks using random sampling, principal component analysis, and basis rotation http://www.medworm.com/index.php?rid=2239771&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F30 Conclusions: We demonstrate how our top-down analysis of networks can be used to determine key regulatory requirements independent of specific parameters and mechanisms. Our approach complements the reductionist approach to elucidation of regulatory mechanisms and facilitates the development of our understanding of global regulatory strategies in biological networks. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2239771 Fri, 06 Mar 2009 05:00:00 +0100 2239771 Simple molecular networks that respond optimally to time periodic stimulation http://www.medworm.com/index.php?rid=2231750&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F29 Conclusions: We present several simple motif designs of molecular networks producing optimal output in response to periodic stimulations of the system. The identified mechanisms are simple and based on known network motifs in the literature, so that that they could be embodied in existing organisms, or easily implementable by means of synthetic biology. Moreover we show that these designs can be studied in different contexts of molecular biology, as for example in genetic networks or in signaling pathways. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2231750 Tue, 03 Mar 2009 05:00:00 +0100 2231750 Protein-protein interaction as a predictor of subcellular location http://www.medworm.com/index.php?rid=2215971&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F28 Conclusion: Understanding cellular systems requires knowledge of the SCL of interacting proteins. We show how PPI data can be used more effectively to yield reliable SCL predictions for both soluble and membrane proteins. Scope exists for further improvement in our understanding of cellular function through consideration of the biological context of molecular interactions. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2215971 Wed, 25 Feb 2009 05:00:00 +0100 2215971 A framework for evolutionary systems biology http://www.medworm.com/index.php?rid=2209435&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F27 Conclusions: EvoSysBio is expected to lead to a more detailed understanding of the fundamental principles of life by combining knowledge about well-known biological systems from several disciplines. This will benefit both evolutionary theory and current systems biology. Understanding robustness by analysing distributions of mutational effects and epistasis is pivotal for drug design, cancer research, responsible genetic engineering in synthetic biology and many other practical applications. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2209435 Tue, 24 Feb 2009 05:00:00 +0100 2209435 Efficient, sparse biological network determination http://www.medworm.com/index.php?rid=2209436&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F25 Conclusions: The presented methodology is able to predict with accuracy and efficiency the connectivity structure of a chemical reaction network with mass action kinetics and a gene regulatory network, although the dynamics of this system are non-polynomial (rational), from simulation data, even when uncertainties in the data are taken into account. It also produces a network structure that can explain the real experimental data of L. lactis and is similar to the one found in the literature. Numerical methods based on Linear Programming can therefore help determine efficiently the network structure of biological systems from large data sets. The overall objective of this work is to provide methods to increase our understanding of complex biochemical systems, particularly through their inte... BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2209436 Mon, 23 Feb 2009 05:00:00 +0100 2209436 Evolution of multiple phosphodiesterase isoforms in stickleback involved in cAMP signal transduction pathway http://www.medworm.com/index.php?rid=2199792&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F23 Conclusions: The predicted effect of the increase in PDE1C products on the OT pathway may play an important role in stickleback behavior and ecology. However, this possibility should be empirically examined. Our analyses imply that an increase in gene product sometimes has a significant, yet unexpected, effect on the functions of subcellular networks. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2199792 Fri, 20 Feb 2009 05:00:00 +0100 2199792 Roles of the Creatine Kinase System and Myoglobin in Maintaining Energetic State in the Working Heart http://www.medworm.com/index.php?rid=2199793&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F22 Conclusions: The CK system stabilizes Delta G_{ATPase} by both buffering ATP and ADP concentrations and enhancing the feedback signal of inorganic phosphate in regulating mitochondrial oxidative phosphorylation. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2199793 Thu, 19 Feb 2009 05:00:00 +0100 2199793 Protein evolution on a human signaling network http://www.medworm.com/index.php?rid=2194528&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F21 Conclusions: Major network constraints on protein evolution in protein interaction networks previously described have been found for signaling networks. We further uncovered how network characteristics affect the evolutionary and co-evolutionary behavior of proteins and how protein evolution can modify the existing functionalities of signaling networks. These new insights provide some general principles for understanding protein evolution in the context of signaling networks. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2194528 Wed, 18 Feb 2009 05:00:00 +0100 2194528 Global transcriptional response of Saccharomyces cerevisiae to the deletion of SDH3 http://www.medworm.com/index.php?rid=2167138&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F17 Conclusions: Our results show that the transcriptional regulatory response resulting from the impaired respiratory function is linked to several different parts of the metabolism, including fatty acid and sterol metabolism. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2167138 Fri, 06 Feb 2009 05:00:00 +0100 2167138 mRNA stability and the unfolding of gene expression in the long-period yeast metabolic cycle http://www.medworm.com/index.php?rid=2167137&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F18 Conclusions: The cascade of events occurring during the yeast metabolic cycle (and their correlation with mRNA turnover) reflects to a large extent the gene expression program observable in other dynamical contexts such as the response to stresses/stimuli. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2167137 Fri, 06 Feb 2009 05:00:00 +0100 2167137 A Drosophila systems model of pentylenetetrazole induced locomotor plasticity responsive to antiepileptic drugs http://www.medworm.com/index.php?rid=2120902&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F11 Conclusions: Systems biology ultimately aims at delineating and comprehending the functioning of complex biological systems in such details that predictive models of human diseases could be developed. Due to immense complexity of higher organisms, systems biology approaches are however currently focused on simpler organisms. Amenable to modeling, our model offers a unique opportunity to further dissect epileptogenesis-like plasticity and to unravel mechanisms of long-term action of AEDs relevant in neuropsychiatric disorders. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2120902 Wed, 21 Jan 2009 05:00:00 +0100 2120902 SNAVI: Desktop application for analysis and visualization of large-scale signaling networks http://www.medworm.com/index.php?rid=2120903&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F10 Conclusions: SNAVI is a useful tool for analyzing, visualizing and sharing cell signaling data. SNAVI is open source free software. The installation may be downloaded from: http://snavi.googlecode.com. The source code can be accessed from: http://snavi.googlecode.com/svn/trunk (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2120903 Tue, 20 Jan 2009 05:00:00 +0100 2120903 Flux balance analysis of primary metabolism in Chlamydomonas reinhardtii http://www.medworm.com/index.php?rid=2115325&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F4 Conclusion: The flux balance analysis model of central and intermediary metabolism in C. reinhardtii is the first such model for algae and the first model to include three metabolically active compartments. In addition to providing estimates of intracellular fluxes, metabolic reconstruction and modelling efforts also provide a comprehensive method for annotation of genome databases. As a result of our reconstruction, one new enzyme was annotated in the database and several others were found to be missing; implying new pathways or non-conserved enzymes. The use of FBA to estimate intracellular fluxes also provides flux values that can be used as a starting point for rational engineering of C. reinhardtii. From these initial estimates, it is clear that aerobic heterotrophic growth on acetate... BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2115325 Wed, 07 Jan 2009 05:00:00 +0100 2115325 Efficiency of complex production in changing environment http://www.medworm.com/index.php?rid=2086672&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F3 Conclusions: In conclusion, these results indicate an intricate regulation at all levels of protein production for the purpose of optimizing complex formation. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2086672 Wed, 07 Jan 2009 05:00:00 +0100 2086672 Modeling ERBB receptor-regulated G1/S transition to find novel targets for de novo trastuzumab resistance http://www.medworm.com/index.php?rid=2073323&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F3%2F1 Conclusions: In this study, we connected ERBB signaling with G1/S transition of the cell cycle via two major cell signaling pathways and two key transcription factors, to model an interaction network that allows for the identification of novel targets in the treatment of trastuzumab resistant breast cancer. Applying this new strategy, we found that, in contrast to trastuzumab sensitive breast cancer cells, combinatorial targeting of ERBB receptors or of key signaling intermediates does not have potential for treatment of de novo trastuzumab resistant cells. Instead, c-MYC was identified as a novel potential target protein in breast cancer cells. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2073323 Thu, 01 Jan 2009 05:00:00 +0100 2073323 Signal duration and the time scale dependence of signal integration in biochemical pathways http://www.medworm.com/index.php?rid=2045803&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F108 Conclusions: We show that multi-staged cascades are effective in integrating signals of long duration whereas multi-staged cascades that operate in the presence of negative feedback are effective in integrating signals of short duration. Our studies suggest principles for why signal duration in connection with multiple steps of downstream regulation is a ubiquitous motif in biochemical systems. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2045803 Wed, 17 Dec 2008 05:00:00 +0100 2045803 Modelling phagosomal lipid networks that regulate actin assembly http://www.medworm.com/index.php?rid=2016819&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F107 Conclusions: By establishing an active 'dialogue' between an initial complex model and experimental observations, we could narrow the set of differential equations and parameters required to characterize the time-dependent changes of metabolites influencing actin nucleation on phagosomes. For this, the global model was dissected into three sub-models: ATP consumption, lipid interconversion, and nucleation of actin on phagosomal membranes. This scheme allowed us to describe this complex system with a relatively small set of differential equations and kinetic parameters that satisfactorily reproduced the experimental data. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=2016819 Fri, 05 Dec 2008 05:00:00 +0100 2016819 A Systematic Molecular Circuit Design Method for Gene Networks under Biochemical Time Delays and Molecular Noises http://www.medworm.com/index.php?rid=1996063&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F103 Conclusions: The proposed gene circuit design method has much potential for application to systems biology, synthetic biology and drug design when a gene regulatory network has to be designed for improving its robust stability and filtering ability of disease-perturbed gene network or when a synthetic gene network needs to perform robustly under process delays and molecular noises. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1996063 Thu, 27 Nov 2008 05:00:00 +0100 1996063 The integrated analysis of metabolic and protein interaction networks reveals novel molecular organizing principles. http://www.medworm.com/index.php?rid=1989722&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F100 Conclusions: Our results reveal topological equivalences between the protein interaction network and the metabolic pathway network. Evolved protein interactions may contribute significantly towards increasing the efficiency of metabolic processes by permitting higher metabolic fluxes. Thus, our results shed further light on the unifying principles shaping the evolution of both the functional (metabolic) as well as the physical interaction network. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1989722 Tue, 25 Nov 2008 05:00:00 +0100 1989722 Genetic and systems level analysis of Drosophila sticky/citron kinase and dFmr1 mutants reveals common regulation of genetic networks http://www.medworm.com/index.php?rid=1989721&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F101 Conclusions: These findings establish a functional link between two previously unrelated genes. Microarray analysis indicates that sticky and dFmr1 are both required for regulation of many developmental genes in a variety of cell types. The diversity of transcripts regulated by these two genes suggests a clear cause of the pleiotropy that sticky and dFmr1 mutants display and provides many novel, testable hypotheses about the functions of these genes. As both of these genes are implicated in the development and function of the mammalian brain, these results have relevance to human health as well as to understanding more general biological processes. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1989721 Tue, 25 Nov 2008 05:00:00 +0100 1989721 Stochastic analysis of the GAL genetic switch in Saccharomyces cerevisiae: Modeling and experiments reveal hierarchy in glucose repression http://www.medworm.com/index.php?rid=1968252&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F97 Conclusions: The mechanisms involved in the transcriptional regulation and their variability set up a hierarchy in the phenotypic response to growth on various substrates. Structural motifs, such as the number of binding sites, and the mechanism of regulation determine the level of stochasticity and eventually the phenotypic response. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1968252 Mon, 17 Nov 2008 05:00:00 +0100 1968252 Natural selection governs local, but not global, evolutionary gene coexpression networks in Caenorhabditis elegans http://www.medworm.com/index.php?rid=1959689&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F96 Conclusion: It appears that selective forces shape how local patterns of coexpression change over time but do not control the global topology of C. elegans evolutionary gene coexpression networks. These results have implications for the evolutionary significance of global network topologies, which are known to be conserved across disparate complex systems. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1959689 Thu, 13 Nov 2008 05:00:00 +0100 1959689 An in silico method for detecting overlapping functional modules from composite biological networks http://www.medworm.com/index.php?rid=1924013&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F93 Conclusions: The successful integration of heterogeneous data and the concept of the proposed algorithm provide confident functional modules. We also proved that our approach is superior to methods restricted to PPI data only. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1924013 Sat, 01 Nov 2008 04:00:00 +0100 1924013 Simulating in vitro transcriptional response of zinc homeostasis system in Escherichia coli http://www.medworm.com/index.php?rid=1900849&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F89 Conclusions: Simulation results show that our model can quantitatively reproduce the results of several of the in vitro experiments conducted by Outten CE and her colleagues. Our model provides a detailed insight into the dynamics of the regulatory system and also provides a general framework for simulating in vitro metal-binding and transcription experiments and interpreting the relevant experimental data. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1900849 Fri, 24 Oct 2008 04:00:00 +0100 1900849 Using a 3D Virtual Muscle model to link gene expression changes during myogenesis to protein spatial location in muscle http://www.medworm.com/index.php?rid=1900850&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F88 Conclusions: By studying gene expression patterns from a structural perspective we have demonstrated that not all genes encoding proteins that are part of muscle specific structures are simply up-regulated during muscle cell differentiation. Indeed, a group of genes whose expression program appears to be minimally affected by the differentiation process, code for proteins participating in vital skeletal muscle structures. Expression alone is a poor metric of gene behaviour. Instead, the "connectivity model of muscle development" is proposed as a mechanism for muscle development: whereby the closer to the myofibril core of muscle cells, the greater the gene expression changes during muscle differentiation and the greater the muscle specificity. (Source: BMC Systems Biology - Latest articles... BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1900850 Wed, 22 Oct 2008 04:00:00 +0100 1900850 Employing conservation of co-expression to improve functional inference http://www.medworm.com/index.php?rid=1815076&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F81 Conclusions: To be able to employ the most suitable co-expression distance measure for our analysis, we evaluated the ability of four popular gene co-expression distance measures to detect biologically relevant interactions between pairs of genes. For the expression datasets employed in our co-expression conservation analysis above, we used the GO and the KEGG PATHWAY databases as gold standards. While the differences between distance measures were small, Spearman correlation showed to give most robust results. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1815076 Mon, 22 Sep 2008 04:00:00 +0100 1815076 Origin of structural difference in metabolic networks with respect to temperature http://www.medworm.com/index.php?rid=1815075&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F82 Conclusions: From the proposed model, we find that such structural properties are determined by the emergence of a short-cut path, which reduces the minimum distance between two nodes on a graph. Furthermore, we investigate correlations between model parameters and growth temperature; as a result, we find that the emergence of the short-cut path tends to be inhibited with increasing temperature. In addition, we also find that the short-cut path bypasses a relatively long path at high temperature when the emergence of the new path is not inhibited. Even further, additional network analysis provides convincing evidence of the reliability of the proposed model and its conclusions on the possible origins of differences in metabolic network structure. (Source: BMC Systems Biology - Latest artic... BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1815075 Mon, 22 Sep 2008 04:00:00 +0100 1815075 On the origin of distribution patterns of motifs in biological networks http://www.medworm.com/index.php?rid=1797560&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F73 Conclusion: Indeed, certain topological features of biological networks give rise naturally to the common appearance of the motifs. We therefore question whether frequencies of occurrences are reasonable evidence that the structures of motifs have been selected for their functional contribution to the operation of networks. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1797560 Tue, 12 Aug 2008 04:00:00 +0100 1797560 On the origin of distribution patterns of motifs in biological networks. http://www.medworm.com/index.php?rid=1700235&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F73 Conclusions: Indeed, certain topological features of biological networks give rise naturally to the common appearance of the motifs. We therefore question whether frequencies of occurrences are reasonable evidence that the structures of motifs have been selected for their functional contribution to the operation of networks. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1700235 Tue, 12 Aug 2008 04:00:00 +0100 1700235 A review of imaging techniques for systems biology http://www.medworm.com/index.php?rid=1700234&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F74 This paper presents a review of imaging techniques and of their utility in system biology. During the last decade systems biology has matured into a distinct field and imaging has been increasingly used to enable the interplay of experimental and theoretical biology. In this review, we describe and compare the roles of microscopy, ultrasound, CT (Computed Tomography), MRI (Magnetic Resonance Imaging), PET (Positron Emission Tomography), and molecular probes such as quantum dots and nanoshells in systems biology. As a unified application area among these different imaging techniques, examples in cancer targeting are highlighted. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1700234 Tue, 12 Aug 2008 04:00:00 +0100 1700234 Constructing disease-specific gene networks using pair-wise relevance metric: application to colon cancer identifies interleukin 8, desmin and enolase 1 as the central elements http://www.medworm.com/index.php?rid=1693553&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F72 Conclusions: This study demonstrated that IL8, DES and ENO1 act as the central elements in colon cancer susceptibility, and protein biosynthesis and the ribosome-associated function categories largely account for the colon cancer tumuorigenesis. Thus, the newly developed relevancy-based networking approach offers a powerful means to reverse-engineer the disease-specific network, a promising tool for systematic dissection of complex diseases. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1693553 Sun, 10 Aug 2008 04:00:00 +0100 1693553 The genome-scale metabolic model iIN800 of Saccharomyces cerevisiae and its validation: a scaffold to query lipid metabolism http://www.medworm.com/index.php?rid=1685924&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F71 Conclusions: We anticipate that performing integrated analyses using iIN800 as a network scaffold will be a valuable tool for elucidating the behavior of complex metabolic networks, particularly for identifying regulatory targets in lipid metabolism that can be used for industrial applications or for understanding lipid disease states. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1685924 Thu, 07 Aug 2008 04:00:00 +0100 1685924 Machine learning based analyses on metabolic networks supports high-throughput knockout screens http://www.medworm.com/index.php?rid=1652097&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F67 Conclusions: Our analysis is feasible to validate experimental knockout data of high throughput screens, can be used to improve flux balance analyses and supports experimental knockout screens to define drug targets. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1652097 Thu, 24 Jul 2008 04:00:00 +0100 1652097 Modeling cellular deformations using the level set formalism http://www.medworm.com/index.php?rid=1652096&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F68 Conclusions: Our results provide a simple but effective means of incorporating cellular deformations into mathematical simulations of cell signaling. Such methods will be useful for simulating important cellular events such as chemotaxis and cytokinesis. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1652096 Thu, 24 Jul 2008 04:00:00 +0100 1652096 Integrated modeling and experimental approach for determining transcription factor profiles from fluorescent reporter data http://www.medworm.com/index.php?rid=1634638&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F64 Conclusions: The technique presented here for computing transcription factor profiles from fluorescence microscopy images of reporter cells generated quantitative data on the magnitude and dynamics of NF-kappaB activation by TNF-alpha. The obtained results are in good agreement with qualitative descriptions of NF-kappaB activation as well as semi-quantitative experimental data from the literature. The profiles computed from the experimental data have been used to re-estimate parameters for a NF-kappaB model and the results of additional experiments are predicted very well by the model with the new parameter values. While the presented approach has been applied to NF-kappaB and TNF-alpha signaling, it can be used to determine the profile of any transcription factor as long as GFP reporter f... BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1634638 Thu, 17 Jul 2008 04:00:00 +0100 1634638 A computational analysis of protein-protein interaction networks in neurodegenerative diseases http://www.medworm.com/index.php?rid=1575158&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F52 Conclusion: Our findings show differential centrality properties of proteins whose gene expression is impaired in neurodegenerative diseases. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1575158 Fri, 20 Jun 2008 04:00:00 +0100 1575158 A computational analysis of the protein-protein interaction networks in neurodegenerative diseases http://www.medworm.com/index.php?rid=1535231&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F52 Conclusion: Our findings show differential centrality properties of proteins whose gene expression is impaired in neurodegenerative diseases. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1535231 Fri, 20 Jun 2008 04:00:00 +0100 1535231 Elucidating the mechanisms of cooperative calcium-calmodulin interactions: a structural systems biology approach http://www.medworm.com/index.php?rid=1487664&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F48 Conclusions: Our model predicts that the specificity and selectivity of CaM target regulation is likely to be due to the following factors: variations in the target-specific Ca2+ dissociation and cooperatively effected dissociation constants, and variations in the number of Ca2+ ions required to bind CaM for target activation. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1487664 Mon, 02 Jun 2008 04:00:00 +0100 1487664 Transcription profiling of lung adenocarcinomas of c-myc-transgenic mice: identification of the c-myc regulatory gene network http://www.medworm.com/index.php?rid=1463470&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F46 Conclusions: Our in silico data suggest a model of a transcriptional regulatory network in which different TFs act in concert upon c-Myc overexpression. We determined molecular rules for transcriptional regulation to explain, in part, the carcinogenic effect seen in mice overexpressing the c-Myc oncogene. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1463470 Thu, 22 May 2008 04:00:00 +0100 1463470 Linear analysis near a steady-state of biochemical networks: control analysis, correlation metrics and circuit theory http://www.medworm.com/index.php?rid=1445640&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F44 Conclusions: One key finding that emerges from this analysis is that the well-known summation theorems in MCA take different forms depending on whether metabolic steady-state is maintained by flux injection or concentration clamping. We demonstrate that if rate-limiting steps exist in a biochemical pathway, they are the steps with smallest biochemical conductances and largest flux control-coefficients. We hypothesize that biochemical networks for cellular signaling have a different strategy for minimizing energy waste and being efficient than do biochemical networks for biosynthesis. We also discuss the intimate relationship between MCA and biochemical systems analysis (BSA). (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1445640 Thu, 15 May 2008 04:00:00 +0100 1445640 SBMLsqueezer: a CellDesigner plug-in to generate kinetic rate equations for biochemical networks http://www.medworm.com/index.php?rid=1409458&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F39 Conclusions: SBMLsqueezer considers the annotation of all participating reactants, products and regulators when generating rate laws for reactions. Thus, for each reaction, only applicable kinetic formulas are considered. This modeling scheme creates kinetics in accordance with the diagrammatic representation. In contrast most previously published tools have relied on the stoichiometry and generic modulators of a reaction, thus ignoring and potentially conflicting with the information expressed through the process diagram. Additional material and the source code can be found at http://www.ra.cs.uni-tuebingen.de/software/SBMLsqueezer (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1409458 Wed, 30 Apr 2008 04:00:00 +0100 1409458 Exploiting the pathway structure of metabolism to reveal high-order epistasis http://www.medworm.com/index.php?rid=1409457&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F40 Conclusions: The complex minimal biomass knockouts discovered with our approach illuminate robust essential systems-level roles for reactions in the E. coli metabolic network. Unlike previous approaches, our method yields results regarding high-order epistatic relationships and is applicable at the genome-scale. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1409457 Wed, 30 Apr 2008 04:00:00 +0100 1409457 Phenotype prediction in regulated metabolic networks http://www.medworm.com/index.php?rid=1399003&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F37 Conclusions: The introduced approach to model a metabolic network and its regulation in an integrated way as one reaction network makes organization analysis a universal technique to study the potential behavior of biological network models. Applying multiple methods like OT and rFBA is shown to be valuable to uncover critical assumptions and helps to improve model coherence. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1399003 Fri, 25 Apr 2008 04:00:00 +0100 1399003 A systems biology approach to analyse amplification in the JAK2-STAT5 signalling pathway http://www.medworm.com/index.php?rid=1399002&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F38 Conclusions: The selected kinetic model predicts that the system acts as an amplifier with maximum amplification and sensitivity for input signals whose intensity match physiological values for Epo concentration and with duration in the range of one to 100 minutes. The response of the system reaches saturation for more intense and longer stimulation with Epo. We hypothesise that these properties of the system directly relate to the saturation of Epo receptor activation, its low recruitment to the plasma membrane and intense deactivation as predicted by the model. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1399002 Fri, 25 Apr 2008 04:00:00 +0100 1399002 A logic-based diagram of signalling pathways central to macrophage activation http://www.medworm.com/index.php?rid=1393630&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F36 Conclusions: The map presents a powerful visual aid for interpreting the available pathway interaction knowledge and underscores the valuable contribution well constructed pathway diagrams make to communicating large amounts of molecular interaction data. Furthermore, we discuss issues with the limitations and scalability of pathways presented in this fashion, explore options for automated layout of large pathway networks and demonstrate how such maps can aid the interpretation of functional studies. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1393630 Wed, 23 Apr 2008 04:00:00 +0100 1393630 Parameter optimization in S-system models http://www.medworm.com/index.php?rid=1376499&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F35 Conclusions: A procedure was developed that facilitates automated reverse engineering tasks for biological networks using S-systems. The proposed method of eigenvector optimization constitutes an advancement over S-system parameter identification from time series using a recent method called Alternating Regression. The proposed method overcomes convergence issues encountered in alternate regression by identifying nonlinear constraints that restrict the search space to computationally feasible solutions. Because the parameter identification is still performed for each metabolite separately, the modularity and linear time characteristics of the alternating regression method are preserved. Simulation studies illustrate how the proposed algorithm identifies the correct network topology out of ... BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1376499 Wed, 16 Apr 2008 04:00:00 +0100 1376499 Using genetic markers to orient the edges in quantitative trait networks: the NEO software http://www.medworm.com/index.php?rid=1373143&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F34 Conclusion: The NEO software can be used to orient the edges of gene co-expression networks or quantitative trait networks if the edges can be anchored to genetic marker data. R software tutorials, data, and supplementary material can be downloaded from: www.genetics.ucla.edu/labs/horvath/aten/NEO. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1373143 Tue, 15 Apr 2008 04:00:00 +0100 1373143 Extracting expression modules from perturbational gene expression compendia http://www.medworm.com/index.php?rid=1363598&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F33 Conclusions: It is increasingly recognized that perturbational expression compendia are essential to identify the gene networks underlying cellular function, and efforts to build these for different organisms are currently underway. We show that ENIGMA constitutes a valuable addition to the repertoire of methods to analyze such data. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1363598 Thu, 10 Apr 2008 04:00:00 +0100 1363598 The dynamics and efficacy of antiviral RNA silencing: a model study http://www.medworm.com/index.php?rid=1328796&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F28 Conclusions: The model presented here is an important step in the understanding of the natural functioning of RNA silencing in viral infections. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1328796 Wed, 26 Mar 2008 04:00:00 +0100 1328796 Hybrid optimization for 13C metabolic flux analysis using systems parametrized by compactification http://www.medworm.com/index.php?rid=1328795&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F29 Conclusion: This fast, robust and accurate optimization method is useful for high-throughput metabolic flux analysis, a posteriori identification of possible parameter correlations, and also for Monte Carlo simulations to obtain statistical qualities for flux estimates. In this way, it contributes to future quantitative studies of central metabolic networks in the framework of systems biology. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1328795 Wed, 26 Mar 2008 04:00:00 +0100 1328795 A stochastic automaton shows how enzyme assemblies may contribute to metabolic efficiency http://www.medworm.com/index.php?rid=1324260&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F27 Conclusions: in silico experiments may be performed successfully using stochastic automata such as HSIM (Hyperstructure SIMulator) to help answer fundamental questions in metabolism about the properties of molecular assemblies and to devise strategies to modify such assemblies for biotechnological ends. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1324260 Tue, 25 Mar 2008 04:00:00 +0100 1324260 One Hub-One Process: a tool based view on regulatory network topology http://www.medworm.com/index.php?rid=1277508&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F25 Conclusion: Our results suggest that local topological features of regulatory networks, including broad degree distributions, emerge as an implicit result of matching a number of needed processes to a finite toolbox of proteins. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1277508 Tue, 04 Mar 2008 05:00:00 +0100 1277508 OptCircuit: an optimization based method for computational design of genetic circuits http://www.medworm.com/index.php?rid=1275811&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F24 Conclusions: Our results demonstrate that OptCircuit framework can serve as a design platform to aid in the construction and finetuning of integrated biological circuits. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1275811 Mon, 03 Mar 2008 05:00:00 +0100 1275811 The regulatory network of E. coli metabolism as a Boolean dynamical system exhibits both homeostasis and flexibility of response http://www.medworm.com/index.php?rid=1268195&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F21 Conclusions: Our study shows that the reconstructed genetic network regulating metabolism in E. coli is hierarchical, modular, and largely acyclic, with environmental variables controlling the root of the hierarchy. This architecture makes the cell highly robust to perturbations of gene configurations as well as highly responsive to environmental changes. The twin properties of homeostasis and response flexibility are achieved by this dynamical system even though it is not close to the edge of chaos. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1268195 Fri, 29 Feb 2008 05:00:00 +0100 1268195 Global parameter search reveals design principles of the mammalian circadian clock http://www.medworm.com/index.php?rid=1268194&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F22 Conclusions: Our work shows that a careful exploration of parameter space for even an extremely simplified model of the mammalian clock can reveal unexpected behaviours and non-trivial predictions. Our results suggest that the neurotransmitter feedback loop plays a crucial role in the robustness and phase resetting properties of the mammalian clock, even at the single neuron level. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1268194 Fri, 29 Feb 2008 05:00:00 +0100 1268194 Interactive analysis of systems biology molecular expression data http://www.medworm.com/index.php?rid=1268193&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F23 Conclusions: The SysNet program has been utilized to analyze elemental profile changes in response to an increasing concentration of iron (Fe) in growth media (an ionomics dataset). This study case demonstrates that the SysNet software is an effective platform for interactive analysis of molecular expression information in systems biology. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1268193 Fri, 29 Feb 2008 05:00:00 +0100 1268193 Reconstruction and analysis of the genetic and metabolic regulatory networks of the central metabolism of Bacillus subtilis http://www.medworm.com/index.php?rid=1257803&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F20 Conclusion: This work reveals the strong involvement of metabolite pools in the general regulation of the metabolic network. Breaking the metabolic network down into elementary modules based on the control of metabolite pools reveals the functional organization of the genetic and metabolic regulatory networks of B. subtilis. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1257803 Tue, 26 Feb 2008 05:00:00 +0100 1257803 Comprehensive proteomic analysis of bovine spermatozoa of varying fertility rates and identification of biomarkers associated with fertility http://www.medworm.com/index.php?rid=1251064&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F19 Conclusion: This is the first comprehensive description of the bovine spermatozoa proteome. Comparative proteomic analysis of high fertility and low fertility bulls, in the context of protein interaction networks identified putative molecular markers associated with high fertility phenotype. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1251064 Fri, 22 Feb 2008 05:00:00 +0100 1251064 Dissecting the logical types of network control in gene expression profiles http://www.medworm.com/index.php?rid=1241574&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F18 Conclusions: By revealing two distinct logical types of control, our approach provides basic insights into both the organizational principles of transcriptional regulation and the mechanisms buffering genetic flexibility. We anticipate that the general concept of distinguishing logical types of control will apply to many complex biological networks. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1241574 Tue, 19 Feb 2008 05:00:00 +0100 1241574 Architecture of transcriptional regulatory circuits is knitted over the topology of bio-molecular interaction networks http://www.medworm.com/index.php?rid=1217773&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F17 Conclusions: Reporter Features offer the opportunity to identify regulatory hot-spots in bio-molecular interaction networks that are significantly affected between or across conditions. Results of the Reporter Feature analysis not only provide a snapshot of the transcriptional regulatory program but also are biologically easy to interpret and provide a powerful way to generate new hypotheses. Our Reporter Features analyses of yeast glucose repression and human diabetes data brings hints towards the understanding of the principles of transcriptional regulation controlling these two important and potentially closely related systems. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1217773 Fri, 08 Feb 2008 05:00:00 +0100 1217773 Three factors underlying incorrect in silico predictions of essential metabolic genes http://www.medworm.com/index.php?rid=1199737&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F14 Conclusions: The results presented herein indicate genes that cannot be correctly predicted as essential have commonalities in different organisms. These elucidated failure modes can be used to better understand the biology of individual organisms and to improve future predictions. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1199737 Mon, 04 Feb 2008 05:00:00 +0100 1199737 Evidence of probabilistic behaviour in protein interaction networks http://www.medworm.com/index.php?rid=1191175&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F11 Conclusions: The results suggest that protein-protein interaction networks incorporate probabilistic elements that lead to scale-rich hierarchical architectures. These observations seem to be at odds with a biologically-guided organization. One interpretation of the findings is that we are witnessing the ability of proteins to indiscriminately bind rather than the protein-protein interactions that are actually utilized by the cell in biological processes. Therefore, the topological study of a degree-weighted network requires a more refined methodology to extract biological information about pathways, modules, or other inferred relationships among proteins. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1191175 Thu, 31 Jan 2008 05:00:00 +0100 1191175 On cycles in the transcription network of Saccharomyces cerevisiae http://www.medworm.com/index.php?rid=1191174&cid=s_34051_67_f&fid=34051&url=http%3A%2F%2Fwww.biomedcentral.com%2F1752-0509%2F2%2F12 Conclusions: Apart from those well-defined conditions, the transcription network of S. cerevisiae is devoid of cycles. It was observed that two conditions that were studied and that have no cycles of their own are exogenous: diauxic shift and DNA repair, while cell cycle and sporulation are endogenous. We claim that in a certain sense (slow recovery) stress response is endogenous as well. (Source: BMC Systems Biology - Latest articles) BMC Systems Biology - Latest articles journals http://www.medworm.com/rss/comments.php?id=1191174 Thu, 31 Jan 2008 05:00:00 +0100 1191174