Publications
211 results found
Wang B, Barahona M, Buck M, 2014, Engineering modular and tunable genetic amplifiers for scaling transcriptional signals in cascaded gene networks, Nucleic Acids Research
Synthetic biology aims to control and reprogram signal processing pathways within living cells so as to realize repurposed, beneficial applications. Here we report the design and construction of a set of modular and gain-tunable genetic amplifiers in Escherichia coli capable of amplifying a transcriptional signal with wide tunable-gain control in cascaded gene networks. The devices are engineered using orthogonal genetic components (hrpRS, hrpV and PhrpL) from the hrp (hypersensitive response and pathogenicity) gene regulatory network in Pseudomonas syringae. The amplifiers can linearly scale up to 21-fold the transcriptional input with a large output dynamic range, yet not introducing significant time delay or significant noise during signal amplification. The set of genetic amplifiers achieves different gains and input dynamic ranges by varying the expression levels of the underlying ligand-free activator proteins in the device. As their electronic counterparts, these engineered transcriptional amplifiers can act as fundamental building blocks in the design of biological systems by predictably and dynamically modulating transcriptional signal flows to implement advanced intra- and extra-cellular control functions.
Noseda M, Harada M, Mcsweeney S, et al., 2014, PDGFRalpha demarcates the cardiogenic and clonogenic Sca-1+stem cell, 3rd Congress of the ESC-Council-on-Basic-Cardiovascular-Science on Frontiers in Cardio Vascular Biology, Publisher: OXFORD UNIV PRESS, ISSN: 0008-6363
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- Citations: 2
Lambiotte R, Delvenne JC, Barahona M, 2014, Random walks, Markov processes and the multiscale modular organization of complex networks, IEEE Transactions on Network Science and Engineering, Vol: 1, Pages: 76-90
Most methods proposed to uncover communities in complex networks rely on combinatorial graph properties. Usually an edge-counting quality function, such as modularity, is optimized over all partitions of the graph compared against a null random graph model. Here we introduce a systematic dynamical framework to design and analyze a wide variety of quality functions for community detection. The quality of a partition is measured by its Markov Stability, a time-parametrized function defined in terms of the statistical properties of a Markov process taking place on the graph. The Markov process provides a dynamical sweeping across all scales in the graph, and the time scale is an intrinsic parameter that uncovers communities at different resolutions. This dynamic-based community detection leads to a compound optimization, which favours communities of comparable centrality (as defined by the stationary distribution), and provides a unifying framework for spectral algorithms, as well as different heuristics for community detection, including versions of modularity and Potts model. Our dynamic framework creates a systematic link between different stochastic dynamics and their corresponding notions of optimal communities under distinct (node and edge) centralities. We show that the Markov Stability can be computed efficiently to find multi-scale community structure in large networks.
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- Citations: 225
Liu Y, Kaneda R, Leja TW, et al., 2014, Hhex and Cer1 mediate the Sox17 pathway for cardiac mesoderm formation in embryonic stem cells., Stem Cells, Vol: 32, Pages: 1515-1526
Cardiac muscle differentiation in vivo is guided by sequential growth factor signals, including endoderm-derived diffusible factors, impinging on cardiogenic genes in the developing mesoderm. Previously, by RNA interference in AB2.2 mouse embryonic stem cells (mESCs), we identified the endodermal transcription factor Sox17 as essential for Mesp1 induction in primitive mesoderm and subsequent cardiac muscle differentiation. However, downstream effectors of Sox17 remained to be proven functionally. In this study, we used genome-wide profiling of Sox17-dependent genes in AB2.2 cells, RNA interference, chromatin immunoprecipitation, and luciferase reporter genes to dissect this pathway. Sox17 was required not only for Hhex (a second endodermal transcription factor) but also for Cer1, a growth factor inhibitor from endoderm that, like Hhex, controls mesoderm patterning in Xenopus toward a cardiac fate. Suppressing Hhex or Cer1 blocked cardiac myogenesis, although at a later stage than induction of Mesp1/2. Hhex was required but not sufficient for Cer1 expression. Over-expression of Sox17 induced endogenous Cer1 and sequence-specific transcription of a Cer1 reporter gene. Forced expression of Cer1 was sufficient to rescue cardiac differentiation in Hhex-deficient cells. Thus, Hhex and Cer1 are indispensable components of the Sox17 pathway for cardiopoiesis in mESCs, acting at a stage downstream from Mesp1/2.
Schaub MT, Lehmann J, Yaliraki SN, et al., 2014, Structure of complex networks: Quantifying edge-to-edge relations by failure-induced flow redistribution, Network Science, Vol: 2, Pages: 66-89
The analysis of complex networks has so far revolved mainly around the role of nodes and communities of nodes. However, the dynamics of interconnected systems is often focalized on edge processes, and a dual edge-centric perspective can often prove more natural. Here we present graph-theoretical measures to quantify edge-to-edge relations inspired by the notion of flow redistribution induced by edge failures. Our measures, which are related to the pseudo-inverse of the Laplacian of the network, are global and reveal the dynamical interplay between the edges of a network, including potentially non-local interactions. Our framework also allows us to define the embeddedness of an edge, a measure of how strongly an edge features in the weighted cuts of the network. We showcase the general applicability of our edge-centric framework through analyses of the Iberian power grid, traffic flow in road networks, and the C. elegans neuronal network.
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- Citations: 35
Branch T, Evans M, Barahona M, et al., 2014, Kinetics of Metal Amyloid-Beta Binding and Efficacy of Ligands Targeting Metal Amyloid-Beta Interactions, 58th Annual Meeting of the Biophysical-Society, Publisher: CELL PRESS, Pages: 39A-39A, ISSN: 0006-3495
Branch T, Barahona M, Ying L, 2014, Kinetics of the Interconversion Between Two Physiologically Important Copper-Bound Amyloid-Beta Species, 58th Annual Meeting of the Biophysical-Society, Publisher: CELL PRESS, Pages: 682A-682A, ISSN: 0006-3495
Amor B, Yaliraki SN, Woscholski R, et al., 2014, Uncovering allosteric pathways in caspase-1 using Markov transient analysis and multiscale community detection, MOLECULAR BIOSYSTEMS, Vol: 10, Pages: 2247-2258, ISSN: 1742-206X
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- Citations: 21
Schumacher J, Behrends V, Pan Z, et al., 2013, Nitrogen and Carbon Status Are Integrated at the Transcriptional Level by the Nitrogen Regulator NtrC <i>In Vivo</i>, MBIO, Vol: 4, ISSN: 2150-7511
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- Citations: 45
O'Clery N, Yuan Y, Stan G-B, et al., 2013, Observability and coarse graining of consensus dynamics through the external equitable partition, PHYSICAL REVIEW E, Vol: 88, ISSN: 1539-3755
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- Citations: 48
Wang B, Barahona M, Buck M, et al., 2013, Rewiring cell signalling through chimaeric regulatory protein engineering, BIOCHEMICAL SOCIETY TRANSACTIONS, Vol: 41, Pages: 1195-1200, ISSN: 0300-5127
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- Citations: 17
Bovens SM, Foin N, O'Clery N, et al., 2013, Shear stress and nitric oxide transport affect NFkB dynamics in endothelial cells, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 110-110, ISSN: 0195-668X
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- Citations: 1
Delvenne J-C, Schaub MT, Yaliraki S, et al., 2013, The stability of a graph partition: A dynamics-based framework for community detection, Dynamics On and Of Complex Networks, Volume 2, Editors: Mukherjee, Choudhury, Peruani, Ganguly, Mitra, Publisher: Springer, Pages: 221-242, ISBN: 978-1-4614-6728-1
Recent years have seen a surge of interest in the analysis of complexnetworks, facilitated by the availability of relational data and theincreasingly powerful computational resources that can be employed for theiranalysis. Naturally, the study of real-world systems leads to highly complexnetworks and a current challenge is to extract intelligible, simplifieddescriptions from the network in terms of relevant subgraphs, which can provideinsight into the structure and function of the overall system. Sparked by seminal work by Newman and Girvan, an interesting line of researchhas been devoted to investigating modular community structure in networks,revitalising the classic problem of graph partitioning. However, modular or community structure in networks has notoriously evadedrigorous definition. The most accepted notion of community is perhaps that of agroup of elements which exhibit a stronger level of interaction withinthemselves than with the elements outside the community. This concept hasresulted in a plethora of computational methods and heuristics for communitydetection. Nevertheless a firm theoretical understanding of most of thesemethods, in terms of how they operate and what they are supposed to detect, isstill lacking to date. Here, we will develop a dynamical perspective towards community detectionenabling us to define a measure named the stability of a graph partition. Itwill be shown that a number of previously ad-hoc defined heuristics forcommunity detection can be seen as particular cases of our method providing uswith a dynamic reinterpretation of those measures. Our dynamics-based approachthus serves as a unifying framework to gain a deeper understanding of differentaspects and problems associated with community detection and allows us topropose new dynamically-inspired criteria for community structure.
Arpino JAJ, Hancock EJ, Anderson J, et al., 2013, Tuning the dials of Synthetic Biology, Microbiology-Sgm, Vol: 159, Pages: 1236-1253, ISSN: 1465-2080
Byrne SL, Yaliraki SN, Barahona M, et al., 2013, Stability analysis of protein kinases, 9th European-Biophysical-Societies-Association Congress, Publisher: SPRINGER, Pages: S174-S174, ISSN: 0175-7571
Yuan Y, Stan G-B, Shi L, et al., 2013, Decentralised minimum-time consensus, AUTOMATICA, Vol: 49, Pages: 1227-1235, ISSN: 0005-1098
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- Citations: 88
Dominguez-Huettinger E, Ono M, Barahona M, et al., 2013, Risk factor-dependent dynamics of atopic dermatitis: modelling multi-scale regulation of epithelium homeostasis, INTERFACE FOCUS, Vol: 3, ISSN: 2042-8898
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- Citations: 11
Sootla A, Strelkowa N, Ernst D, et al., 2013, Toggling a Genetic Switch Using Reinforcement Learning, 9th French Meeting on Planning, Decision Making and Learning
Beguerisse-Diaz M, Vangelov B, Barahona M, 2013, Finding role communities in directed networks using Role-Based Similarity, Markov Stability and the Relaxed Minimum Spanning Tree, 2013 IEEE GLOBAL CONFERENCE ON SIGNAL AND INFORMATION PROCESSING (GLOBALSIP), Pages: 937-940, ISSN: 2376-4066
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- Citations: 17
Georgiou PS, Barahona M, Yaliraki SN, et al., 2013, Ideal Memristors as Reciprocal Elements, Proceedings of the 20th IEEE International Conference on Electronics, Circuits, and Systems (ICECS), Pages: 301-304
Beguerisse-Diaz M, Hernandez-Gomez M, Lizzul A, et al., 2012, Compound stress responses in stomatal closure: a systems model of ABA and ethylene interactions in guard cells, Bmc Systems Biology, Vol: 6
Phoka E, Wildie M, Schultz SR, et al., 2012, Sensory experience modifies spontaneous state dynamics in a large-scale barrel cortical model, JOURNAL OF COMPUTATIONAL NEUROSCIENCE, Vol: 33, Pages: 323-339, ISSN: 0929-5313
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- Citations: 11
Kaloriti D, Tillmann A, Cook E, et al., 2012, Combinatorial stresses kill pathogenic <i>Candida</i> species, MEDICAL MYCOLOGY, Vol: 50, Pages: 699-709, ISSN: 1369-3786
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- Citations: 67
Huettinger ED, Ono M, Barahona M, et al., 2012, Mathematical model of the development of Atopic dermatitis, 22nd IUBMB Congress/37th FEBS Congress, Publisher: WILEY-BLACKWELL, Pages: 523-523, ISSN: 1742-464X
Dominguez-Huttinger E, Ono M, Barahona M, et al., 2012, System-level investigation of risk factors for atopic dermatitis by mathematical modelling and analysis, 42nd Annual Meeting of the European-Society-for-Dermatological-Research (ESDR), Publisher: NATURE PUBLISHING GROUP, Pages: S25-S25, ISSN: 0022-202X
Wang B, Barahona M, Buck M, 2012, A modular cell-based biosensor using engineered genetic logic circuits to detect and integrate multiple environmental signals, Biosensors and Bioelectronics, Vol: 40, Pages: 368-376, ISSN: 0956-5663
Cells perceive a wide variety of cellular and environmental signals, which are often processed combinatorially to generate particular phenotypic responses. Here, we employ both single and mixed cell type populations, pre-programmed with engineered modular cell signalling and sensing circuits, as processing units to detect and integrate multiple environmental signals. Based on an engineered modular genetic AND logic gate, we report the construction of a set of scalable synthetic microbe-based biosensors comprising exchangeable sensory, signal processing and actuation modules. These cellular biosensors were engineered using distinct signalling sensory modules to precisely identify various chemical signals, and combinations thereof, with a quantitative fluorescent output. The genetic logic gate used can function as a biological filter and an amplifier to enhance the sensing selectivity and sensitivity of cell-based biosensors. In particular, an Escherichia coli consortium-based biosensor has been constructed that can detect and integrate three environmental signals (arsenic, mercury and copper ion levels) via either its native two-component signal transduction pathways or synthetic signalling sensors derived from other bacteria in combination with a cell-cell communication module. We demonstrate how a modular cell-based biosensor can be engineered predictably using exchangeable synthetic gene circuit modules to sense and integrate multiple-input signals. This study illustrates some of the key practical design principles required for the future application of these biosensors in broad environmental and healthcare areas.
Schaub MT, Lambiotte R, Barahona M, 2012, Encoding dynamics for multiscale community detection: Markov time sweeping for the map equation, PHYSICAL REVIEW E, Vol: 86, ISSN: 2470-0045
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- Citations: 37
Anderson J, Strelkowa N, Stan G-B, et al., 2012, Engineering and ethical perspectives in synthetic biology, EMBO Reports, Vol: 13, Pages: 584-590, ISSN: 1469-221X
Synthetic biology has emerged as an exciting and promising new research field, garnering significant attention from both the scientific community and the general public. This interest results from a variety of striking features: synthetic biology is a truly interdisciplinary field that engages biologists, mathematicians, physicists and engineers; its research focus is applied; and it has enormous potential to harness the power of biology to provide scientific and engineering solutions to a wide range of problems and challenges that plague humanity. However, the power of synthetic biology to engineer organisms with custom‐made functionality requires that researchers and society use this power safely and responsibly, in particular when it comes to releasing organisms into the environment. This creates new challenges for both the design of such organisms and the regulatory process governing their creation and use.
Sootla A, Strelkowa N, Ernst D, et al., 2012, On Periodic Reference Tracking Using Batch-Mode Reinforcement Learning with Application to Gene Regulatory Network Control, submitted to Conf. Decision Control
In this paper, we consider the periodic referencetracking problem in the framework of batch-mode reinforcement learning, which studies methods for solving optimal control problems from the sole knowledge of a set of trajectories. In particular, we adapt an existing batch-mode reinforcement learning algorithm, known as Fitted Q iteration, to the periodic reference tracking problem. The presented periodic reference tracking algorithm explicitly exploits a priori knowledge of the future values of the reference trajectory and its periodicity. We discuss the properties of our approach and illustrate it onthe problem of reference tracking for a synthetic biology gene regulatory network known as the generalised repressilator. This system can produce decaying but long-lived oscillations, which makes it an interesting system for the tracking problem. In our companion paper submitted to this conference we also take a look at the regulation problem of the toggle switch system, where the main goal is to drive the systems states to a specific bounded region in the state space.
Schaub MT, Delvenne J-C, Yaliraki SN, et al., 2012, Markov Dynamics as a Zooming Lens for Multiscale Community Detection: Non Clique-Like Communities and the Field-of-View Limit, PLOS ONE, Vol: 7, ISSN: 1932-6203
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- Citations: 91
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