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Computation gene circuits

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https://www.readbyqxmd.com/read/28362798/interrogating-the-topological-robustness-of-gene-regulatory-circuits-by-randomization
#1
Bin Huang, Mingyang Lu, Dongya Jia, Eshel Ben-Jacob, Herbert Levine, Jose N Onuchic
One of the most important roles of cells is performing their cellular tasks properly for survival. Cells usually achieve robust functionality, for example, cell-fate decision-making and signal transduction, through multiple layers of regulation involving many genes. Despite the combinatorial complexity of gene regulation, its quantitative behavior has been typically studied on the basis of experimentally verified core gene regulatory circuitry, composed of a small set of important elements. It is still unclear how such a core circuit operates in the presence of many other regulatory molecules and in a crowded and noisy cellular environment...
March 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28361666/towards-targeted-combinatorial-therapy-design-for-the-treatment-of-castration-resistant-prostate-cancer
#2
Osama Ali Arshad, Aniruddha Datta
BACKGROUND: Prostate cancer is one of the most prevalent cancers in males in the United States and amongst the leading causes of cancer related deaths. A particularly virulent form of this disease is castration-resistant prostate cancer (CRPC), where patients no longer respond to medical or surgical castration. CRPC is a complex, multifaceted and heterogeneous malady with limited standard treatment options. RESULTS: The growth and progression of prostate cancer is a complicated process that involves multiple pathways...
March 22, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28355056/deconvolution-of-gene-expression-noise-into-spatial-dynamics-of-transcription-factor-promoter-interplay
#3
Ángel Goñi-Moreno, Ilaria Benedetti, Juhyun Kim, Víctor de Lorenzo
Gene expression noise is not only the mere consequence of stochasticity, but also a signal that reflects the upstream physical dynamics of the cognate molecular machinery. Soil bacteria facing recalcitrant pollutants exploit noise of catabolic promoters to deploy beneficial phenotypes such as metabolic bet-hedging and/or division of biochemical labor. Although the role of upstream promoter-regulator interplay in the origin of this noise is little understood, its specifications are probably ciphered in flow cytometry data patterns...
April 17, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28350462/automated-design-framework-for-synthetic-biology-exploiting-pareto-optimality
#4
Irene Otero-Muras, Julio R Banga
In this work we consider Pareto optimality for automated design in synthetic biology. We present a generalized framework based on a mixed-integer dynamic optimization formulation that, given design specifications, allows the computation of Pareto optimal sets of designs, that is, the set of best trade-offs for the metrics of interest. We show how this framework can be used for (i) forward design, that is, finding the Pareto optimal set of synthetic designs for implementation, and (ii) reverse design, that is, analyzing and inferring motifs and/or design principles of gene regulatory networks from the Pareto set of optimal circuits...
April 12, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28346402/large-scale-design-of-robust-genetic-circuits-with-multiple-inputs-and-outputs-for-mammalian-cells
#5
Benjamin H Weinberg, N T Hang Pham, Leidy D Caraballo, Thomas Lozanoski, Adrien Engel, Swapnil Bhatia, Wilson W Wong
Engineered genetic circuits for mammalian cells often require extensive fine-tuning to perform as intended. We present a robust, general, scalable system, called 'Boolean logic and arithmetic through DNA excision' (BLADE), to engineer genetic circuits with multiple inputs and outputs in mammalian cells with minimal optimization. The reliability of BLADE arises from its reliance on recombinases under the control of a single promoter, which integrates circuit signals on a single transcriptional layer. We used BLADE to build 113 circuits in human embryonic kidney and Jurkat T cells and devised a quantitative, vector-proximity metric to evaluate their performance...
March 27, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28283561/alteration-of-neuronal-excitability-and-short-term-synaptic-plasticity-in-the-prefrontal-cortex-of-a-mouse-model-of-mental-illness
#6
Gregg W Crabtree, Ziyi Sun, Mirna Kvajo, Jantine A C Broek, Karine Fénelon, Heather McKellar, Lan Xiao, Bin Xu, Sabine Bahn, James M O'Donnell, Joseph A Gogos
Using a genetic mouse model that faithfully recapitulates a DISC1 genetic alteration strongly associated with schizophrenia and other psychiatric disorders, we examined the impact of this mutation within the prefrontal cortex. Although cortical layering, cytoarchitecture, and proteome were found to be largely unaffected, electrophysiological examination of the mPFC revealed both neuronal hyperexcitability and alterations in short-term synaptic plasticity consistent with enhanced neurotransmitter release. Increased excitability of layer II/III pyramidal neurons was accompanied by consistent reductions in voltage-activated potassium currents near the action potential threshold as well as by enhanced recruitment of inputs arising from superficial layers to layer V...
April 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28268898/a-large-scale-detailed-neuronal-model-of-electrical-stimulation-of-the-dentate-gyrus-and-perforant-path-as-a-platform-for-electrode-design-and-optimization
#7
Clayton S Bingham, Kyle Loizos, Gene Yu, Andrew Gilbert, Jean-Marie Bouteiller, Dong Song, Gianluca Lazzi, Theodore W Berger
Owing to the dramatic rise in treatment of neurological disorders with electrical micro-stimulation it has become apparent that the major technological limitation in deploying effective devices lies in the process of designing efficient, safe, and outcome specific electrode arrays. The time-consuming and low-fidelity nature of gathering test data using experimental means and the immense control and flexibility of computational models, has prompted us and others to build models of electrical stimulation of neural networks that can be simulated in a computer...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28268605/parameter-estimation-for-gene-regulatory-networks-a-two-stage-mcmc-bayesian-approach
#8
Niannan Xue, Wei Pan, Yike Guo
Genetic regulatory networks have emerged as a useful way to elucidate the biochemical pathways for biological functions. Yet, determination of the exact parametric forms for these models remain a major challenge. In this paper, we present a novel computational approach implemented in C++ to solve this inverse problem. This takes the form of an optimization stage first after which Bayesian filtering takes place. The key advantage of such a flexible, general and robust approach is that it provides us with a joint probability distribution of the model parameters instead of single estimates, which we can propagate to final predictions...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28256619/a-core-regulatory-circuit-in-glioblastoma-stem-cells-links-mapk-activation-to-a-transcriptional-program-of-neural-stem-cell-identity
#9
Gregory Riddick, Svetlana Kotliarova, Virginia Rodriguez, H S Kim, Amanda Linkous, Andrew J Storaska, Susie Ahn, Jennifer Walling, Galina Belova, Howard A Fine
Glioblastoma, the most common primary malignant brain tumor, harbors a small population of tumor initiating cells (glioblastoma stem cells) that have many properties similar to neural stem cells. To investigate common regulatory networks in both neural and glioblastoma stem cells, we subjected both cell types to in-vitro differentiation conditions and measured global gene-expression changes using gene expression microarrays. Analysis of enriched transcription factor DNA-binding sites in the promoters of differentially expressed genes was used to reconstruct regulatory networks involved in differentiation...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28239411/reliable-measurement-of-e-coli-single-cell-fluorescence-distribution-using-a-standard-microscope-set-up
#10
Marilisa Cortesi, Lucia Bandiera, Alice Pasini, Alessandro Bevilacqua, Alessandro Gherardi, Simone Furini, Emanuele Giordano
BACKGROUND: Quantifying gene expression at single cell level is fundamental for the complete characterization of synthetic gene circuits, due to the significant impact of noise and inter-cellular variability on the system's functionality. Commercial set-ups that allow the acquisition of fluorescent signal at single cell level (flow cytometers or quantitative microscopes) are expensive apparatuses that are hardly affordable by small laboratories. METHODS: A protocol that makes a standard optical microscope able to acquire quantitative, single cell, fluorescent data from a bacterial population transformed with synthetic gene circuitry is presented...
2017: Journal of Biological Engineering
https://www.readbyqxmd.com/read/28231449/synthetic-gene-circuits-learn-to-classify
#11
Andriy Didovyk, Lev S Tsimring
An efficient computational algorithm is developed to design microRNA-based synthetic cell classifiers and to optimize their performance.
February 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/28227099/a-large-scale-detailed-neuronal-model-of-electrical-stimulation-of-the-dentate-gyrus-and-perforant-path-as-a-platform-for-electrode-design-and-optimization
#12
Clayton S Bingham, Kyle Loizos, Gene Yu, Andrew Gilbert, Jean-Marie Bouteiller, Dong Song, Gianluca Lazzi, Theodore W Berger, Clayton S Bingham, Kyle Loizos, Gene Yu, Andrew Gilbert, Jean-Marie Bouteiller, Dong Song, Gianluca Lazzi, Theodore W Berger, Kyle Loizos, Gene Yu, Theodore W Berger, Gianluca Lazzi, Jean-Marie Bouteiller, Clayton S Bingham, Dong Song, Andrew Gilbert
Owing to the dramatic rise in treatment of neurological disorders with electrical micro-stimulation it has become apparent that the major technological limitation in deploying effective devices lies in the process of designing efficient, safe, and outcome specific electrode arrays. The time-consuming and low-fidelity nature of gathering test data using experimental means and the immense control and flexibility of computational models, has prompted us and others to build models of electrical stimulation of neural networks that can be simulated in a computer...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226784/parameter-estimation-for-gene-regulatory-networks-a-two-stage-mcmc-bayesian-approach
#13
Niannan Xue, Wei Pan, Yike Guo, Niannan Xue, Wei Pan, Yike Guo, Wei Pan, Yike Guo, Niannan Xue
Genetic regulatory networks have emerged as a useful way to elucidate the biochemical pathways for biological functions. Yet, determination of the exact parametric forms for these models remain a major challenge. In this paper, we present a novel computational approach implemented in C++ to solve this inverse problem. This takes the form of an optimization stage first after which Bayesian filtering takes place. The key advantage of such a flexible, general and robust approach is that it provides us with a joint probability distribution of the model parameters instead of single estimates, which we can propagate to final predictions...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28219373/a-new-efficient-approach-to-fit-stochastic-models-on-the-basis-of-high-throughput-experimental-data-using-a-model-of-irf7-gene-expression-as-case-study
#14
Luis U Aguilera, Christoph Zimmer, Ursula Kummer
BACKGROUND: Mathematical models are used to gain an integrative understanding of biochemical processes and networks. Commonly the models are based on deterministic ordinary differential equations. When molecular counts are low, stochastic formalisms like Monte Carlo simulations are more appropriate and well established. However, compared to the wealth of computational methods used to fit and analyze deterministic models, there is only little available to quantify the exactness of the fit of stochastic models compared to experimental data or to analyze different aspects of the modeling results...
February 20, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28211790/flpstop-a-tool-for-conditional-gene-control-in-drosophila
#15
Yvette E Fisher, Helen H Yang, Jesse Isaacman-Beck, Marjorie Xie, Daryl M Gohl, Thomas R Clandinin
Manipulating gene function cell type-specifically is a common experimental goal in Drosophila research and has been central to studies of neural development, circuit computation, and behavior. However, current cell type-specific gene disruption techniques in flies often reduce gene activity incompletely or rely on cell division. Here we describe FlpStop, a generalizable tool for conditional gene disruption and rescue in post-mitotic cells. In proof-of-principle experiments, we manipulated apterous, a regulator of wing development...
February 17, 2017: ELife
https://www.readbyqxmd.com/read/28166866/genetic-control-of-encoding-strategy-in-a-food-sensing-neural-circuit
#16
Giovanni Diana, Dhaval S Patel, Eugeni V Entchev, Mei Zhan, Hang Lu, QueeLim Ch'ng
Neuroendocrine circuits encode environmental information via changes in gene expression and other biochemical activities to regulate physiological responses. Previously, we showed that daf-7 TGFβ and tph-1 tryptophan hydroxylase expression in specific neurons encode food abundance to modulate lifespan in Caenorhabditis elegans, and uncovered cross- and self-regulation among these genes (Entchev et al., 2015). Here, we now extend these findings by showing that these interactions between daf-7 and tph-1 regulate redundancy and synergy among neurons in food encoding through coordinated control of circuit-level signal and noise properties...
February 7, 2017: ELife
https://www.readbyqxmd.com/read/28103878/synthetic-circuits-that-process-multiple-light-and-chemical-signal-inputs
#17
Lizhong Liu, Wei Huang, Jian-Dong Huang
BACKGROUND: Multi-signal processing circuits are essential for rational design of sophisticated synthetic systems with good controllability and modularity, therefore, enable construction of high-level networks. Moreover, light-inducible systems provide fast and reversible means for spatiotemporal control of gene expression. RESULTS: Here, in HEK 293 cells, we present combinatory genetic circuits responding to light and chemical signals, simultaneously. We first constructed a dual input circuit converting different light intensities into varying of the sensitivity of the promoter to a chemical inducer (doxycycline)...
January 19, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/27927198/a-computational-method-for-the-investigation-of-multistable-systems-and-its-application-to-genetic-switches
#18
Miriam Leon, Mae L Woods, Alex J H Fedorec, Chris P Barnes
BACKGROUND: Genetic switches exhibit multistability, form the basis of epigenetic memory, and are found in natural decision making systems, such as cell fate determination in developmental pathways. Synthetic genetic switches can be used for recording the presence of different environmental signals, for changing phenotype using synthetic inputs and as building blocks for higher-level sequential logic circuits. Understanding how multistable switches can be constructed and how they function within larger biological systems is therefore key to synthetic biology...
December 7, 2016: BMC Systems Biology
https://www.readbyqxmd.com/read/27865452/cyp2a6-genetic-variation-alters-striatal-cingulate-circuits-network-hubs-and-executive-processing-in-smokers
#19
Sufang Li, Yihong Yang, Ewa Hoffmann, Rachel F Tyndale, Elliot A Stein
BACKGROUND: Variation in the CYP2A6 gene alters the rate of nicotine metabolic inactivation and is associated with smoking behaviors and cessation success rates. The underlying neurobiological mechanisms of this genetic influence are unknown. METHODS: Intrinsic functional connectivity strength, a whole-brain, data-driven, graph theory-based method, was applied to resting-state functional magnetic resonance imaging data in 66 smokers and 92 nonsmokers. A subset of subjects (n = 23/20; smokers/nonsmokers) performed the monetary incentive delay task, probing reward anticipation, and a go/no-go task, probing response inhibition, on two occasions, in the presence and absence of a nicotine patch...
April 1, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/27857683/in-vitro-magnetic-stimulation-a-simple-stimulation-device-to-deliver-defined-low-intensity-electromagnetic-fields
#20
Stephanie Grehl, David Martina, Catherine Goyenvalle, Zhi-De Deng, Jennifer Rodger, Rachel M Sherrard
Non-invasive brain stimulation (NIBS) by electromagnetic fields appears to benefit human neurological and psychiatric conditions, although the optimal stimulation parameters and underlying mechanisms remain unclear. Although, in vitro studies have begun to elucidate cellular mechanisms, stimulation is delivered by a range of coils (from commercially available human stimulation coils to laboratory-built circuits) so that the electromagnetic fields induced within the tissue to produce the reported effects are ill-defined...
2016: Frontiers in Neural Circuits
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