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BMC Systems Biology

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https://www.readbyqxmd.com/read/28841879/an-integrative-multi-lineage-model-of-variation-in-leukopoiesis-and-acute-myelogenous-leukemia
#1
Joyatee M Sarker, Serena M Pearce, Robert P Nelson, Tamara L Kinzer-Ursem, David M Umulis, Ann E Rundell
BACKGROUND: Acute myelogenous leukemia (AML) progresses uniquely in each patient. However, patients are typically treated with the same types of chemotherapy, despite biological differences that lead to differential responses to treatment. RESULTS: Here we present a multi-lineage multi-compartment model of the hematopoietic system that captures patient-to-patient variation in both the concentration and rates of change of hematopoietic cell populations. By constraining the model against clinical hematopoietic cell recovery data derived from patients who have received induction chemotherapy, we identified trends for parameters that must be met by the model; for example, the mitosis rates and the probability of self-renewal of progenitor cells are inversely related...
August 25, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28807050/cooperative-binding-mitigates-the-high-dose-hook-effect
#2
Ranjita Dutta Roy, Christian Rosenmund, Melanie I Stefan
BACKGROUND: The high-dose hook effect (also called prozone effect) refers to the observation that if a multivalent protein acts as a linker between two parts of a protein complex, then increasing the amount of linker protein in the mixture does not always increase the amount of fully formed complex. On the contrary, at a high enough concentration range the amount of fully formed complex actually decreases. It has been observed that allosterically regulated proteins seem less susceptible to this effect...
August 14, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28800759/quantitative-reproducibility-analysis-for-identifying-reproducible-targets-from-high-throughput-experiments
#3
Wenfei Zhang, Ying Liu, Mindy Zhang, Cheng Zhu, Yuefeng Lu
BACKGROUND: High-throughput assays are widely used in biological research to select potential targets. One single high-throughput experiment can efficiently study a large number of candidates simultaneously, but is subject to substantial variability. Therefore it is scientifically important to performance quantitative reproducibility analysis to identify reproducible targets with consistent and significant signals across replicate experiments. A few methods exist, but all have limitations...
August 11, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28754124/manatee-invariants-reveal-functional-pathways-in-signaling-networks
#4
Leonie Amstein, Jörg Ackermann, Jennifer Scheidel, Simone Fulda, Ivan Dikic, Ina Koch
BACKGROUND: Signal transduction pathways are important cellular processes to maintain the cell's integrity. Their imbalance can cause severe pathologies. As signal transduction pathways feature complex regulations, they form intertwined networks. Mathematical models aim to capture their regulatory logic and allow an unbiased analysis of robustness and vulnerability of the signaling network. Pathway detection is yet a challenge for the analysis of signaling networks in the field of systems biology...
July 28, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28754122/snoopy-s-hybrid-simulator-a-tool-to-construct-and-simulate-hybrid-biological-models
#5
Mostafa Herajy, Fei Liu, Christian Rohr, Monika Heiner
BACKGROUND: Hybrid simulation of (computational) biochemical reaction networks, which combines stochastic and deterministic dynamics, is an important direction to tackle future challenges due to complex and multi-scale models. Inherently hybrid computational models of biochemical networks entail two time scales: fast and slow. Therefore, it is intricate to efficiently and accurately analyse them using only either deterministic or stochastic simulation. However, there are only a few software tools that support such an approach...
July 28, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28724377/combination-therapy-for-melanoma-with-braf-mek-inhibitor-and-immune-checkpoint-inhibitor-a-mathematical-model
#6
Xiulan Lai, Avner Friedman
BACKGROUND: The B-raf gene is mutated in up to 66% of human malignant melanomas, and its protein product, BRAF kinase, is a key part of RAS-RAF-MEK-ERK (MAPK) pathway of cancer cell proliferation. BRAF-targeted therapy induces significant responses in the majority of patients, and the combination BRAF/MEK inhibitor enhances clinical efficacy, but the response to BRAF inhibitor and to BRAF/MEK inhibitor is short lived. On the other hand, treatment of melanoma with an immune checkpoint inhibitor, such as anti-PD-1, has lower response rate but the response is much more durable, lasting for years...
July 19, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28716030/modeling-de-novo-granulation-of-anaerobic-sludge
#7
Anna Doloman, Honey Varghese, Charles D Miller, Nicholas S Flann
BACKGROUND: A unique combination of mechanical, physiochemical and biological forces influences granulation during processes of anaerobic digestion. Understanding this process requires a systems biology approach due to the need to consider not just single-cell metabolic processes, but also the multicellular organization and development of the granule. RESULTS: In this computational experiment, we address the role that physiochemical and biological processes play in granulation and provide a literature-validated working model of anaerobic granule de novo formation...
July 17, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28693620/development-of-an-in-silico-method-for-the-identification-of-subcomplexes-involved-in-the-biogenesis-of-multiprotein-complexes-in-saccharomyces-cerevisiae
#8
Annie Glatigny, Philippe Gambette, Alexa Bourand-Plantefol, Geneviève Dujardin, Marie-Hélène Mucchielli-Giorgi
BACKGROUND: Large sets of protein-protein interaction data coming either from biological experiments or predictive methods are available and can be combined to construct networks from which information about various cell processes can be extracted. We have developed an in silico approach based on these information to model the biogenesis of multiprotein complexes in the yeast Saccharomyces cerevisiae. RESULTS: Firstly, we have built three protein interaction networks by collecting the protein-protein interactions, which involved the subunits of three complexes, from different databases...
July 11, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28693495/an-agent-based-model-of-triple-negative-breast-cancer-the-interplay-between-chemokine-receptor-ccr5-expression-cancer-stem-cells-and-hypoxia
#9
Kerri-Ann Norton, Travis Wallace, Niranjan B Pandey, Aleksander S Popel
BACKGROUND: Triple-negative breast cancer lacks estrogen, progesterone, and HER2 receptors and is thus not possible to treat with targeted therapies for these receptors. Therefore, a greater understanding of triple-negative breast cancer is necessary for the treatment of this cancer type. In previous work from our laboratory, we found that chemokine ligand-receptor CCL5-CCR5 axis is important for the metastasis of human triple-negative breast cancer cell MDA-MB-231 to the lymph nodes and lungs, in a mouse xenograft model...
July 11, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28676050/reconstruction-of-the-microalga-nannochloropsis-salina-genome-scale-metabolic-model-with-applications-to-lipid-production
#10
Nicolás Loira, Sebastian Mendoza, María Paz Cortés, Natalia Rojas, Dante Travisany, Alex Di Genova, Natalia Gajardo, Nicole Ehrenfeld, Alejandro Maass
BACKGROUND: Nannochloropsis salina (= Eustigmatophyceae) is a marine microalga which has become a biotechnological target because of its high capacity to produce polyunsaturated fatty acids and triacylglycerols. It has been used as a source of biofuel, pigments and food supplements, like Omega 3. Only some Nannochloropsis species have been sequenced, but none of them benefit from a genome-scale metabolic model (GSMM), able to predict its metabolic capabilities. RESULTS: We present iNS934, the first GSMM for N...
July 4, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28659168/gene-expression-profiles-and-signaling-mechanisms-in-%C3%AE-2b-adrenoceptor-evoked-proliferation-of-vascular-smooth-muscle-cells
#11
Anna Huhtinen, Vesa Hongisto, Asta Laiho, Eliisa Löyttyniemi, Dirk Pijnenburg, Mika Scheinin
BACKGROUND: α2-adrenoceptors are important regulators of vascular tone and blood pressure. Regulation of cell proliferation is a less well investigated consequence of α2-adrenoceptor activation. We have previously shown that α2B-adrenoceptor activation stimulates proliferation of vascular smooth muscle cells (VSMCs). This may be important for blood vessel development and plasticity and for the pathology and therapeutics of cardiovascular disorders. The underlying cellular mechanisms have remained mostly unknown...
June 28, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28651594/the-cd4-t-cell-regulatory-network-mediates-inflammatory-responses-during-acute-hyperinsulinemia-a-simulation-study
#12
Mariana E Martinez-Sanchez, Marcia Hiriart, Elena R Alvarez-Buylla
BACKGROUND: Obesity is frequently linked to insulin resistance, high insulin levels, chronic inflammation, and alterations in the behaviour of CD4+ T cells. Despite the biomedical importance of this condition, the system-level mechanisms that alter CD4+ T cell differentiation and plasticity are not well understood. RESULTS: We model how hyperinsulinemia alters the dynamics of the CD4+ T regulatory network, and this, in turn, modulates cell differentiation and plasticity...
June 26, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28646868/comprehensive-benchmarking-of-markov-chain-monte-carlo-methods-for-dynamical-systems
#13
Benjamin Ballnus, Sabine Hug, Kathrin Hatz, Linus Görlitz, Jan Hasenauer, Fabian J Theis
BACKGROUND: In quantitative biology, mathematical models are used to describe and analyze biological processes. The parameters of these models are usually unknown and need to be estimated from experimental data using statistical methods. In particular, Markov chain Monte Carlo (MCMC) methods have become increasingly popular as they allow for a rigorous analysis of parameter and prediction uncertainties without the need for assuming parameter identifiability or removing non-identifiable parameters...
June 24, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28629365/evaluation-and-improvement-of-the-regulatory-inference-for-large-co-expression-networks-with-limited-sample-size
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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