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BMC Systems Biology

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https://www.readbyqxmd.com/read/28629365/evaluation-and-improvement-of-the-regulatory-inference-for-large-co-expression-networks-with-limited-sample-size
#1
Wenbin Guo, Cristiane P G Calixto, Nikoleta Tzioutziou, Ping Lin, Robbie Waugh, John W S Brown, Runxuan Zhang
BACKGROUND: Co-expression has been widely used to identify novel regulatory relationships using high throughput measurements, such as microarray and RNA-seq data. Evaluation studies on co-expression network analysis methods mostly focus on networks of small or medium size of up to a few hundred nodes. For large networks, simulated expression data usually consist of hundreds or thousands of profiles with different perturbations or knock-outs, which is uncommon in real experiments due to their cost and the amount of work required...
June 19, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28619054/hgpec-a-cytoscape-app-for-prediction-of-novel-disease-gene-and-disease-disease-associations-and-evidence-collection-based-on-a-random-walk-on-heterogeneous-network
#2
Duc-Hau Le, Van-Huy Pham
BACKGROUND: Finding gene-disease and disease-disease associations play important roles in the biomedical area and many prioritization methods have been proposed for this goal. Among them, approaches based on a heterogeneous network of genes and diseases are considered state-of-the-art ones, which achieve high prediction performance and can be used for diseases with/without known molecular basis. RESULTS: Here, we developed a Cytoscape app, namely HGPEC, based on a random walk with restart algorithm on a heterogeneous network of genes and diseases...
June 15, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28606124/remodeling-adipose-tissue-through-in-silico-modulation-of-fat-storage-for-the-prevention-of-type-2-diabetes
#3
Thierry Chénard, Frédéric Guénard, Marie-Claude Vohl, André Carpentier, André Tchernof, Rafael J Najmanovich
BACKGROUND: Type 2 diabetes is one of the leading non-infectious diseases worldwide and closely relates to excess adipose tissue accumulation as seen in obesity. Specifically, hypertrophic expansion of adipose tissues is related to increased cardiometabolic risk leading to type 2 diabetes. Studying mechanisms underlying adipocyte hypertrophy could lead to the identification of potential targets for the treatment of these conditions. RESULTS: We present iTC1390adip, a highly curated metabolic network of the human adipocyte presenting various improvements over the previously published iAdipocytes1809...
June 12, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28583118/single-cell-study-links-metabolism-with-nutrient-signaling-and-reveals-sources-of-variability
#4
Niek Welkenhuysen, Johannes Borgqvist, Mattias Backman, Loubna Bendrioua, Mattias Goksör, Caroline B Adiels, Marija Cvijovic, Stefan Hohmann
BACKGROUND: The yeast AMPK/SNF1 pathway is best known for its role in glucose de/repression. When glucose becomes limited, the Snf1 kinase is activated and phosphorylates the transcriptional repressor Mig1, which is then exported from the nucleus. The exact mechanism how the Snf1-Mig1 pathway is regulated is not entirely elucidated. RESULTS: Glucose uptake through the low affinity transporter Hxt1 results in nuclear accumulation of Mig1 in response to all glucose concentrations upshift, however with increasing glucose concentration the nuclear localization of Mig1 is more intense...
June 5, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28571567/clostridium-butyricum-maximizes-growth-while-minimizing-enzyme-usage-and-atp-production-metabolic-flux-distribution-of-a-strain-cultured-in-glycerol
#5
Luis Miguel Serrano-Bermúdez, Andrés Fernando González Barrios, Costas D Maranas, Dolly Montoya
BACKGROUND: The increase in glycerol obtained as a byproduct of biodiesel has encouraged the production of new industrial products, such as 1,3-propanediol (PDO), using biotechnological transformation via bacteria like Clostridium butyricum. However, despite the increasing role of Clostridium butyricum as a bio-production platform, its metabolism remains poorly modeled. RESULTS: We reconstructed iCbu641, the first genome-scale metabolic (GSM) model of a PDO producer Clostridium strain, which included 641 genes, 365 enzymes, 891 reactions, and 701 metabolites...
June 1, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28521769/modeling-the-dynamics-of-mouse-iron-body-distribution-hepcidin-is-necessary-but-not-sufficient
#6
Jignesh H Parmar, Grey Davis, Hope Shevchuk, Pedro Mendes
BACKGROUND: Iron is an essential element of most living organisms but is a dangerous substance when poorly liganded in solution. The hormone hepcidin regulates the export of iron from tissues to the plasma contributing to iron homeostasis and also restricting its availability to infectious agents. Disruption of iron regulation in mammals leads to disorders such as anemia and hemochromatosis, and contributes to the etiology of several other diseases such as cancer and neurodegenerative diseases...
May 18, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28511648/a-mathematical-model-of-mechanotransduction-reveals-how-mechanical-memory-regulates-mesenchymal-stem-cell-fate-decisions
#7
Tao Peng, Linan Liu, Adam L MacLean, Chi Wut Wong, Weian Zhao, Qing Nie
BACKGROUND: Mechanical and biophysical properties of the cellular microenvironment regulate cell fate decisions. Mesenchymal stem cell (MSC) fate is influenced by past mechanical dosing (memory), but the mechanisms underlying this process have not yet been well defined. We have yet to understand how memory affects specific cell fate decisions, such as the differentiation of MSCs into neurons, adipocytes, myocytes, and osteoblasts. RESULTS: We study a minimal gene regulatory network permissive of multi-lineage MSC differentiation into four cell fates...
May 16, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28511646/emergence-of-microbial-diversity-due-to-cross-feeding-interactions-in-a-spatial-model-of-gut-microbial-metabolism
#8
Milan J A van Hoek, Roeland M H Merks
BACKGROUND: The human gut contains approximately 10(14) bacteria, belonging to hundreds of different species. Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e...
May 16, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28476119/parameter-identifiability-analysis-and-visualization-in-large-scale-kinetic-models-of-biosystems
#9
Attila Gábor, Alejandro F Villaverde, Julio R Banga
BACKGROUND: Kinetic models of biochemical systems usually consist of ordinary differential equations that have many unknown parameters. Some of these parameters are often practically unidentifiable, that is, their values cannot be uniquely determined from the available data. Possible causes are lack of influence on the measured outputs, interdependence among parameters, and poor data quality. Uncorrelated parameters can be seen as the key tuning knobs of a predictive model. Therefore, before attempting to perform parameter estimation (model calibration) it is important to characterize the subset(s) of identifiable parameters and their interplay...
May 5, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28472965/parameter-identifiability-based-optimal-observation-remedy-for-biological-networks
#10
Yulin Wang, Hongyu Miao
BACKGROUND: To systematically understand the interactions between numerous biological components, a variety of biological networks on different levels and scales have been constructed and made available in public databases or knowledge repositories. Graphical models such as structural equation models have long been used to describe biological networks for various quantitative analysis tasks, especially key biological parameter estimation. However, limited by resources or technical capacities, partial observation is a common problem in experimental observations of biological networks, and it thus becomes an important problem how to select unobserved nodes for additional measurements such that all unknown model parameters become identifiable...
May 4, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28446174/a-scalable-metabolite-supplementation-strategy-against-antibiotic-resistant-pathogen-chromobacterium-violaceum-induced-by-nad-nadh-imbalance
#11
Deepanwita Banerjee, Dharmeshkumar Parmar, Nivedita Bhattacharya, Avinash D Ghanate, Venkateswarlu Panchagnula, Anu Raghunathan
BACKGROUND: The leading edge of the global problem of antibiotic resistance necessitates novel therapeutic strategies. This study develops a novel systems biology driven approach for killing antibiotic resistant pathogens using benign metabolites. RESULTS: Controlled laboratory evolutions established chloramphenicol and streptomycin resistant pathogens of Chromobacterium. These resistant pathogens showed higher growth rates and required higher lethal doses of antibiotic...
April 26, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28446158/parameter-inference-for-stochastic-single-cell-dynamics-from-lineage-tree-data
#12
Irena Kuzmanovska, Andreas Milias-Argeitis, Jan Mikelson, Christoph Zechner, Mustafa Khammash
BACKGROUND: With the advance of experimental techniques such as time-lapse fluorescence microscopy, the availability of single-cell trajectory data has vastly increased, and so has the demand for computational methods suitable for parameter inference with this type of data. Most of currently available methods treat single-cell trajectories independently, ignoring the mother-daughter relationships and the information provided by the population structure. However, this information is essential if a process of interest happens at cell division, or if it evolves slowly compared to the duration of the cell cycle...
April 26, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28420402/sser-species-specific-essential-reactions-database
#13
Abraham A Labena, Yuan-Nong Ye, Chuan Dong, Fa-Z Zhang, Feng-Biao Guo
BACKGROUND: Essential reactions are vital components of cellular networks. They are the foundations of synthetic biology and are potential candidate targets for antimetabolic drug design. Especially if a single reaction is catalyzed by multiple enzymes, then inhibiting the reaction would be a better option than targeting the enzymes or the corresponding enzyme-encoding gene. The existing databases such as BRENDA, BiGG, KEGG, Bio-models, Biosilico, and many others offer useful and comprehensive information on biochemical reactions...
April 19, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28412970/membrane-potential-independent-transport-of-nh3-in-the-absence-of-ammonium-permeases-in-saccharomyces-cerevisiae
#14
Hugo F Cueto-Rojas, Nicholas Milne, Ward van Helmond, Mervin M Pieterse, Antonius J A van Maris, Jean-Marc Daran, S Aljoscha Wahl
BACKGROUND: Microbial production of nitrogen containing compounds requires a high uptake flux and assimilation of the N-source (commonly ammonium), which is generally coupled with ATP consumption and negatively influences the product yield. In the industrial workhorse Saccharomyces cerevisiae, ammonium (NH4(+)) uptake is facilitated by ammonium permeases (Mep1, Mep2 and Mep3), which transport the NH4(+) ion, resulting in ATP expenditure to maintain the intracellular charge balance and pH by proton export using the plasma membrane-bound H(+)-ATPase...
April 17, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28407804/mathematical-model-of-tgf-%C3%AE-signalling-feedback-coupling-is-consistent-with-signal-switching
#15
Shabnam Khatibi, Hong-Jian Zhu, John Wagner, Chin Wee Tan, Jonathan H Manton, Antony W Burgess
BACKGROUND: Transforming growth factor β (TGF-β) signalling regulates the development of embryos and tissue homeostasis in adults. In conjunction with other oncogenic changes, long-term perturbation of TGF-β signalling is associated with cancer metastasis. Although TGF-β signalling can be complex, many of the signalling components are well defined, so it is possible to develop mathematical models of TGF-β signalling using reduction and scaling methods. The parameterization of our TGF-β signalling model is consistent with experimental data...
April 13, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28403906/an-additional-k-means-clustering-step-improves-the-biological-features-of-wgcna-gene-co-expression-networks
#16
Juan A Botía, Jana Vandrovcova, Paola Forabosco, Sebastian Guelfi, Karishma D'Sa, John Hardy, Cathryn M Lewis, Mina Ryten, Michael E Weale
BACKGROUND: Weighted Gene Co-expression Network Analysis (WGCNA) is a widely used R software package for the generation of gene co-expression networks (GCN). WGCNA generates both a GCN and a derived partitioning of clusters of genes (modules). We propose k-means clustering as an additional processing step to conventional WGCNA, which we have implemented in the R package km2gcn (k-means to gene co-expression network, https://github.com/juanbot/km2gcn ). RESULTS: We assessed our method on networks created from UKBEC data (10 different human brain tissues), on networks created from GTEx data (42 human tissues, including 13 brain tissues), and on simulated networks derived from GTEx data...
April 12, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28395655/sbpipe-a-collection-of-pipelines-for-automating-repetitive-simulation-and-analysis-tasks
#17
Piero Dalle Pezze, Nicolas Le Novère
BACKGROUND: The rapid growth of the number of mathematical models in Systems Biology fostered the development of many tools to simulate and analyse them. The reliability and precision of these tasks often depend on multiple repetitions and they can be optimised if executed as pipelines. In addition, new formal analyses can be performed on these repeat sequences, revealing important insights about the accuracy of model predictions. RESULTS: Here we introduce SBpipe, an open source software tool for automating repetitive tasks in model building and simulation...
April 10, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28381275/quantitative-evaluation-and-reversion-analysis-of-the-attractor-landscapes-of-an-intracellular-regulatory-network-for-colorectal-cancer
#18
Yunseong Kim, Sea Choi, Dongkwan Shin, Kwang-Hyun Cho
BACKGROUND: Cancer reversion, converting the phenotypes of a cancer cell into those of a normal cell, has been sporadically observed throughout history. However, no systematic analysis has been attempted so far. RESULTS: To investigate this from a systems biological perspective, we have constructed a logical network model of colorectal tumorigenesis by integrating key regulatory molecules and their interactions from previous experimental data. We identified molecular targets that can reverse cancerous cellular states to a normal state by systematically perturbing each molecular activity in the network and evaluating the resulting changes of the attractor landscape with respect to uncontrolled proliferation, EMT, and stemness...
April 5, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28376924/period-doubling-cascades-of-limit-cycles-in-cardiac-action-potential-models-as-precursors-to-chaotic-early-afterdepolarizations
#19
Philipp Kügler, M A K Bulelzai, André H Erhardt
BACKGROUND: Early afterdepolarizations (EADs) are pathological voltage oscillations during the repolarization phase of cardiac action potentials (APs). EADs are caused by drugs, oxidative stress or ion channel disease, and they are considered as potential precursors to cardiac arrhythmias in recent attempts to redefine the cardiac drug safety paradigm. The irregular behaviour of EADs observed in experiments has been previously attributed to chaotic EAD dynamics under periodic pacing, made possible by a homoclinic bifurcation in the fast subsystem of the deterministic AP system of differential equations...
April 4, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28376810/rewiring-of-the-inferred-protein-interactome-during-blood-development-studied-with-the-tool-ppicompare
#20
Thorsten Will, Volkhard Helms
BACKGROUND: Differential analysis of cellular conditions is a key approach towards understanding the consequences and driving causes behind biological processes such as developmental transitions or diseases. The progress of whole-genome expression profiling enabled to conveniently capture the state of a cell's transcriptome and to detect the characteristic features that distinguish cells in specific conditions. In contrast, mapping the physical protein interactome for many samples is experimentally infeasible at the moment...
April 4, 2017: BMC Systems Biology
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