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BMC Systems Biology

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https://www.readbyqxmd.com/read/28521769/modeling-the-dynamics-of-mouse-iron-body-distribution-hepcidin-is-necessary-but-not-sufficient
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/28376782/image-analysis-driven-single-cell-analytics-for-systems-microbiology
#16
Athanasios D Balomenos, Panagiotis Tsakanikas, Zafiro Aspridou, Anastasia P Tampakaki, Konstantinos P Koutsoumanis, Elias S Manolakos
BACKGROUND: Time-lapse microscopy is an essential tool for capturing and correlating bacterial morphology and gene expression dynamics at single-cell resolution. However state-of-the-art computational methods are limited in terms of the complexity of cell movies that they can analyze and lack of automation. The proposed Bacterial image analysis driven Single Cell Analytics (BaSCA) computational pipeline addresses these limitations thus enabling high throughput systems microbiology. RESULTS: BaSCA can segment and track multiple bacterial colonies and single-cells, as they grow and divide over time (cell segmentation and lineage tree construction) to give rise to dense communities with thousands of interacting cells in the field of view...
April 4, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28347313/estimating-genome-wide-regulatory-activity-from-multi-omics-data-sets-using-mathematical-optimization
#17
Saskia Trescher, Jannes Münchmeyer, Ulf Leser
BACKGROUND: Gene regulation is one of the most important cellular processes, indispensable for the adaptability of organisms and closely interlinked with several classes of pathogenesis and their progression. Elucidation of regulatory mechanisms can be approached by a multitude of experimental methods, yet integration of the resulting heterogeneous, large, and noisy data sets into comprehensive and tissue or disease-specific cellular models requires rigorous computational methods. Recently, several algorithms have been proposed which model genome-wide gene regulation as sets of (linear) equations over the activity and relationships of transcription factors, genes and other factors...
March 27, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28340582/optimisation-of-an-exemplar-oculomotor-model-using-multi-objective-genetic-algorithms-executed-on-a-gpu-cpu-combination
#18
Eleftherios Avramidis, Ozgur E Akman
BACKGROUND: Parameter optimisation is a critical step in the construction of computational biology models. In eye movement research, computational models are increasingly important to understanding the mechanistic basis of normal and abnormal behaviour. In this study, we considered an existing neurobiological model of fast eye movements (saccades), capable of generating realistic simulations of: (i) normal horizontal saccades; and (ii) infantile nystagmus - pathological ocular oscillations that can be subdivided into different waveform classes...
March 24, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28302111/quantifying-the-roles-of-random-motility-and-directed-motility-using-advection-diffusion-theory-for-a-3t3-fibroblast-cell-migration-assay-stimulated-with-an-electric-field
#19
Matthew J Simpson, Kai-Yin Lo, Yung-Shin Sun
BACKGROUND: Directed cell migration can be driven by a range of external stimuli, such as spatial gradients of: chemical signals (chemotaxis); adhesion sites (haptotaxis); or temperature (thermotaxis). Continuum models of cell migration typically include a diffusion term to capture the undirected component of cell motility and an advection term to capture the directed component of cell motility. However, there is no consensus in the literature about the form that the advection term takes...
March 17, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28298210/delineating-functional-principles-of-the-bow-tie-structure-of-a-kinase-phosphatase-network-in-the-budding-yeast
#20
Diala Abd-Rabbo, Stephen W Michnick
BACKGROUND: Kinases and phosphatases (KP) form complex self-regulating networks essential for cellular signal processing. In spite of having a wealth of data about interactions among KPs and their substrates, we have very limited models of the structures of the directed networks they form and consequently our ability to formulate hypotheses about how their structure determines the flow of information in these networks is restricted. RESULTS: We assembled and studied the largest bona fide kinase-phosphatase network (KP-Net) known to date for the yeast Saccharomyces cerevisiae...
March 16, 2017: BMC Systems Biology
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