Publications
103 results found
Johnston IG, Burgstaller JP, Havlicek V, et al., 2015, Stochastic modelling, Bayesian inference, and new in vivo measurements elucidate the debated mtDNA bottleneck mechanism, eLife, Vol: 4, ISSN: 2050-084X
Dangerous damage to mitochondrial DNA (mtDNA) can be ameliorated during mammalian development through a highly debated mechanism called the mtDNA bottleneck. Uncertainty surrounding this process limits our ability to address inherited mtDNA diseases. We produce a new, physically motivated, generalisable theoretical model for mtDNA populations during development, allowing the first statistical comparison of proposed bottleneck mechanisms. Using approximate Bayesian computation and mouse data, we find most statistical support for a combination of binomial partitioning of mtDNAs at cell divisions and random mtDNA turnover, meaning that the debated exact magnitude of mtDNA copy number depletion is flexible. New experimental measurements from a wild-derived mtDNA pairing in mice confirm the theoretical predictions of this model. We analytically solve a mathematical description of this mechanism, computing probabilities of mtDNA disease onset, efficacy of clinical sampling strategies, and effects of potential dynamic interventions, thus developing a quantitative and experimentally-supported stochastic theory of the bottleneck.
Hoitzing H, Johnston IG, Jones NS, 2015, What is the function of mitochondrial networks? A theoretical assessment of hypotheses and proposal for future research, Bioessays, Vol: 37, Pages: 687-700, ISSN: 1521-1878
Mitochondria can change their shape from discrete isolated organelles to a large continuous reticulum. The cellular advantages underlying these fused networks are still incompletely understood. In this paper, we describe and compare hypotheses regarding the function of mitochondrial networks. We use mathematical and physical tools both to investigate existing hypotheses and to generate new ones, and we suggest experimental and modelling strategies. Among the novel insights we underline from this work are the possibilities that (i) selective mitophagy is not required for quality control because selective fusion is sufficient; (ii) increased connectivity may have non-linear effects on the diffusion rate of proteins; and (iii) fused networks can act to dampen biochemical fluctuations. We hope to convey to the reader that quantitative approaches can drive advances in the understanding of the physiological advantage of these morphological changes.
de Figueiredo A, Johnston I, Smith DMD, et al., 2015, Changing socioeconomic determinants of childhood vaccines: a global analysis over three decades, LANCET GLOBAL HEALTH, Vol: 3, Pages: 20-20, ISSN: 2214-109X
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- Citations: 3
Preston J, Binner JM, Branicki L, et al., 2015, City evacuations: An interdisciplinary approach, ISBN: 9783662438763
Evacuating a city is a complex problem that involves issues of governance, preparedness education, warning, information sharing, population dynamics, resilience and recovery. As natural and anthropogenic threats to cities grow, it is an increasingly pressing problem for policy makers and practitioners. The book is the result of a unique interdisciplinary collaboration between researchers in the physical and social sciences to consider how an interdisciplinary approach can help plan for large scale evacuations.nbsp;It draws on perspectives from physics, mathematics, organisation theory, economics, sociology and education.nbsp;Importantly it goes beyond disciplinary boundaries and considers how interdisciplinary methods are necessary to approach a complex problem involving human actors and increasingly complex communications and transportation infrastructures. Using real world case studies and modelling the book considers new approaches to evacuation dynamics. It addresses questions of complexity, not only in terms of theory, but examining the latest challenges for cities and emergency responders. Factors such as social media, information quality and visualisation techniques are examined to consider the 'new' dynamics of warning and informing, evacuation and recovery.
King J, Jones N, King J, 2015, Simulation of information spreading following a crisis, City Evacuations: An Interdisciplinary Approach, Pages: 39-62, ISBN: 9783662438763
In this chapter we consider how information about a crisis spreads. We consider scenarios, and models thereof, which are variants of the susceptible/infected model from epidemiology. The populace is initially unaware that a crisis has occurred. When the crisis begins, awareness that a crisis has occurred spreads throughout the populace via a combination of broadcast media and social feedback; eventually the entire populace becomes aware of the crisis. We investigate transitions in our models from a completely unaware populace to a completely aware populace, focusing particularly on the speed of the process and the relative impact of different media types. Our models’ behaviour depends heavily on the input parameters which dictate the strengths of different spreading mechanisms. As much as possible we draw values for these parameters from real data. These parameters vary significantly depending on the time of day. For example, the number of people who become aware almost immediately because they are tuned in to broadcast media when the crisis occurs ranges from about 2% to about 47%. In addition, the timescale on which an alert unfolds means that our models should incorporate dynamic parameters, i.e., parameters that change as the alert unfolds. With regard to the relative impact of different media types in our models, we note that, within our model, social media such as Facebook and Twitter are much less important than traditional media, primarily by virtue of their smaller audience and less frequent use. We also identify a critical timescale: the length of time it takes someone with the TV/Radio on to realize there is a crisis and then to relate it to someone else. This realize-and-relate timescale is likely to have an important role in shaping the early course of events in daytime crisis spreading.
Johnston IG, Rickett BC, Jones NS, 2014, Explicit Tracking of Uncertainty Increases the Power of Quantitative Rule-of-Thumb Reasoning in Cell Biology, BIOPHYSICAL JOURNAL, Vol: 107, Pages: 2612-2617, ISSN: 0006-3495
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- Citations: 13
Schwarzlaender M, Wagner S, Ermakova YG, et al., 2014, The 'mitoflash' probe cpYFP does not respond to superoxide, NATURE, Vol: 514, Pages: E12-E14, ISSN: 0028-0836
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- Citations: 100
El Zawily AM, Schwarzlaender M, Finkemeier I, et al., 2014, <i>FRIENDLY</i> Regulates Mitochondrial Distribution, Fusion, and Quality Control in Arabidopsis, PLANT PHYSIOLOGY, Vol: 166, Pages: 808-U517, ISSN: 0032-0889
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- Citations: 57
Burgstaller JP, Johnston IG, Jones NS, et al., 2014, mtDNA Segregation in Heteroplasmic Tissues Is Common In Vivo and Modulated by Haplotype Differences and Developmental Stage, CELL REPORTS, Vol: 7, Pages: 2031-2041, ISSN: 2211-1247
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- Citations: 75
Fulcher BD, Little MA, Jones NS, 2013, Highly comparative time-series analysis: the empirical structure of time series and their methods, Journal of the Royal Society Interface, Vol: 10, ISSN: 1742-5689
The process of collecting and organizing sets of observations represents a common theme throughout the history of science. However, despite the ubiquity of scientists measuring, recording and analysing the dynamics of different processes, an extensive organization of scientific time-series data and analysis methods has never been performed. Addressing this, annotated collections of over 35 000 real-world and model-generated time series, and over 9000 time-series analysis algorithms are analysed in this work. We introduce reduced representations of both time series, in terms of their properties measured by diverse scientific methods, and of time-series analysis methods, in terms of their behaviour on empirical time series, and use them to organize these interdisciplinary resources. This new approach to comparing across diverse scientific data and methods allows us to organize time-series datasets automatically according to their properties, retrieve alternatives to particular analysis methods developed in other scientific disciplines and automate the selection of useful methods for time-series classification and regression tasks. The broad scientific utility of these tools is demonstrated on datasets of electroencephalograms, self-affine time series, heartbeat intervals, speech signals and others, in each case contributing novel analysis techniques to the existing literature. Highly comparative techniques that compare across an interdisciplinary literature can thus be used to guide more focused research in time-series analysis for applications across the scientific disciplines.
Jones NS, Hadjipantelis PZ, Moriarty J, et al., 2013, Function-valued traits in evolution, Interface, Vol: 10, Pages: 1-8, ISSN: 1742-5662
Many biological characteristics of evolutionary interest are not scalar variables but continuous functions. Given a dataset of function-valued traits generated by evolution, we develop a practical, statistical approach to infer ancestral function-valued traits, and estimate the generative evolutionary process. We do this by combining dimension reduction and phylogenetic Gaussian process regression, a non-parametric procedure that explicitly accounts for known phylogenetic relationships. We test the performance of methods on simulated, function-valued data generated from a stochastic evolutionary model. The methods are applied assuming that only the phylogeny, and the function-valued traits of taxa at its tips are known. Our method is robust and applicable to a wide range of function-valued data, and also offers a phylogenetically aware method for estimating the autocorrelation of function-valued traits.
Little MA, Jones NS, 2013, Signal processing for molecular and cellular biological physics: an emerging field, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES, Vol: 371, ISSN: 1364-503X
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- Citations: 10
Jones NS, Maccarone TJ, 2013, Inference for the physical sciences Introduction, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES, Vol: 371, ISSN: 1364-503X
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- Citations: 1
Jones NS, Moriarty J, 2013, Evolutionary inference for function-valued traits: Gaussian process regression on phylogenies, JOURNAL OF THE ROYAL SOCIETY INTERFACE, Vol: 10, ISSN: 1742-5689
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- Citations: 15
Onnela J-P, Fenn DJ, Reid S, et al., 2012, Taxonomies of networks from community structure, PHYSICAL REVIEW E, Vol: 86, ISSN: 2470-0045
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- Citations: 69
Lewis ACF, Jones NS, Porter MA, et al., 2012, What Evidence Is There for the Homology of Protein-Protein Interactions?, PLOS COMPUTATIONAL BIOLOGY, Vol: 8, ISSN: 1553-734X
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- Citations: 29
Heaton LLM, Lopez E, Maini PK, et al., 2012, Advection, diffusion, and delivery over a network, PHYSICAL REVIEW E, Vol: 86, ISSN: 1539-3755
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- Citations: 34
Heaton L, Obara B, Grau V, et al., 2012, Analysis of fungal networks, Fungal Biology Reviews, Vol: 26, Pages: 12-29, ISSN: 1749-4613
Johnston IG, Gaal B, Neves RPD, et al., 2012, Mitochondrial Variability as a Source of Extrinsic Cellular Noise, PLoS Comput Biol, Vol: 8
<title>Author Summary</title> <p>Cellular variability has been found to play a major role in diverse and important phenomena, including stem cell differentiation and drug resistance, but the sources of this variability have yet to be satisfactorily explained. We propose a mechanism, supported by a substantial number of recent and new experiments, by which cell-to-cell differences in both the number and functionality of mitochondria – the organelles responsible for energy production in eukaryotes – leads to variability in transcription rate between cells and may hence be a significant source of cellular noise in many downstream processes. We illustrate the downstream effect of mitochondrial variability through simulated studies of protein expression and stem cell differentiation, and suggest possible experimental approaches to further elucidate this mechanism.</p>
Schwarzlander M, Logan DC, Johnston IG, et al., 2012, Pulsing of Membrane Potential in Individual Mitochondria: A Stress-Induced Mechanism to Regulate Respiratory Bioenergetics in Arabidopsis, The Plant Cell, Vol: 24, Pages: 1188-1201
Mitochondrial ATP synthesis is driven by a membrane potential across the inner mitochondrial membrane; this potential is generated by the proton-pumping electron transport chain. A balance between proton pumping and dissipation of the proton gradient by ATP-synthase is critical to avoid formation of excessive reactive oxygen species due to overreduction of the electron transport chain. Here, we report a mechanism that regulates bioenergetic balance in individual mitochondria: a transient partial depolarization of the inner membrane. Single mitochondria in living Arabidopsis thaliana root cells undergo sporadic rapid cycles of partial dissipation and restoration of membrane potential, as observed by real-time monitoring of the fluorescence of the lipophilic cationic dye tetramethyl rhodamine methyl ester. Pulsing is induced in tissues challenged by high temperature, H2O2, or cadmium. Pulses were coincident with a pronounced transient alkalinization of the matrix and are therefore not caused by uncoupling protein or by the opening of a nonspecific channel, which would lead to matrix acidification. Instead, a pulse is the result of Ca2+ influx, which was observed coincident with pulsing; moreover, inhibitors of calcium transport reduced pulsing. We propose a role for pulsing as a transient uncoupling mechanism to counteract mitochondrial dysfunction and reactive oxygen species production.
Aston JAD, Buck D, Coleman J, et al., 2012, Phylogenetic inference for function-valued traits: speech sound evolution, Trends Ecol Evol, Vol: 27, Pages: 160-166, ISSN: 0169-5347
Phylogenetic models have recently been proposed for data that are best represented as a mathematical function (i.e. function valued). Such methods can be used to model the change over time in function-based descriptions of various data of interest to evolutionary biologists, including the sound of speech. This approach to phylogenetic inference and analysis is challenging, both in terms of modeling the phylogenetics of functions and in engaging with previously existing evidence for character-state change. Nevertheless, it is both a real and exciting prospect. Our approach could provide those interested in investigating a greater range of evolutionary processes with the ability to use statistical hypothesis-testing procedures and to create estimates of the states of function-valued characteristics (e.g. speech sounds) at earlier historical times.
Fenn DJ, Porter MA, Mucha PJ, et al., 2012, Dynamical clustering of exchange rates, QUANTITATIVE FINANCE, Vol: 12, Pages: 1493-1520, ISSN: 1469-7688
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- Citations: 40
Little MA, Jones NS, 2011, Generalized methods and solvers for noise removal from piecewise constant signals. I. Background theory, PROCEEDINGS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES, Vol: 467, Pages: 3088-3114, ISSN: 1364-5021
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- Citations: 71
Little MA, Jones NS, 2011, Generalized methods and solvers for noise removal from piecewise constant signals. II. New methods, PROCEEDINGS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES, Vol: 467, Pages: 3115-3140, ISSN: 1364-5021
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- Citations: 27
Fenn DJ, Porter MA, Williams S, et al., 2011, Temporal evolution of financial-market correlations, PRE, Vol: 84
Little MA, Steel BC, Bai F, et al., 2011, Steps and Bumps: Precision Extraction of Discrete States of Molecular Machines, BIOPHYSICAL JOURNAL, Vol: 101, Pages: 477-485, ISSN: 0006-3495
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- Citations: 23
das Neves RP, Jones NS, Andreu L, et al., 2010, Connecting variability in global transcription rate to mitochondrial variability, PLOS Biology, Vol: 8, ISSN: 1545-7885
Populations of genetically identical eukaryotic cells show significant cell-to-cell variability in gene expression. However, welack a good understanding of the origins of this variation. We have found marked cell-to-cell variability in average cellularrates of transcription. We also found marked cell-to-cell variability in the amount of cellular mitochondrial mass. Weundertook fusion studies that suggested that variability in transcription rate depends on small diffusible factors. Followingthis, in vitro studies showed that transcription rate has a sensitive dependence on [ATP] but not on the concentration ofother nucleotide triphosphates (NTPs). Further experiments that perturbed populations by changing nutrient levels andavailable [ATP] suggested this connection holds in vivo. We found evidence that cells with higher mitochondrial mass, orhigher total membrane potential, have a faster rate of transcription per unit volume of nuclear material. We also foundevidence that transcription rate variability is substantially modulated by the presence of anti- or prooxidants. Daughterstudies showed that a cause of variability in mitochondrial content is apparently stochastic segregation of mitochondria atdivision. We conclude by noting that daughters that stochastically inherit a lower mitochondrial mass than their sisters haverelatively longer cell cycles. Our findings reveal a link between variability in energy metabolism and variability intranscription rate.
Heaton LLM, López E, Maini PK, et al., 2010, Growth-induced mass flows in fungal networks, Proceedings of the Royal Society B: Biological Sciences, Vol: 277, Pages: 3265-3274
Cord-forming fungi form extensive networks that continuously adapt to maintain an efficient transport system. As osmotically driven water uptake is often distal from the tips, and aqueous fluids are incompressible, we propose that growth induces mass flows across the mycelium, whether or not there are intrahyphal concentration gradients. We imaged the temporal evolution of networks formed by Phanerochaete velutina, and at each stage calculated the unique set of currents that account for the observed changes in cord volume, while minimizing the work required to overcome viscous drag. Predicted speeds were in reasonable agreement with experimental data, and the pressure gradients needed to produce these flows are small. Furthermore, cords that were predicted to carry fast-moving or large currents were significantly more likely to increase in size than cords with slow-moving or small currents. The incompressibility of the fluids within fungi means there is a rapid global response to local fluid movements. Hence velocity of fluid flow is a local signal that conveys quasi-global information about the role of a cord within the mycelium. We suggest that fluid incompressibility and the coupling of growth and mass flow are critical physical features that enable the development of efficient, adaptive biological transport networks.
Lewis ACF, Jones NS, Porter MA, et al., 2010, The function of communities in protein interaction networks at multiple scales, BMC Systems Biology
Agarwal S, Deane CM, Porter MA, et al., 2010, Revisiting date and party hubs: novel approaches to role assignment in protein interaction networks, PLOS Computational Biology, Vol: 6, ISSN: 1553-734X
The idea of “date” and “party” hubs has been influential in the study of protein–protein interaction networks. Date hubs display low co-expression with their partners, whilst party hubs have high co-expression. It was proposed that party hubs are local coordinators whereas date hubs are global connectors. Here, we show that the reported importance of date hubs to network connectivity can in fact be attributed to a tiny subset of them. Crucially, these few, extremely central, hubs do not display particularly low expression correlation, undermining the idea of a link between this quantity and hub function. The date/party distinction was originally motivated by an approximately bimodal distribution of hub co-expression; we show that this feature is not always robust to methodological changes. Additionally, topological properties of hubs do not in general correlate with co-expression. However, we find significant correlations between interaction centrality and the functional similarity of the interacting proteins. We suggest that thinking in terms of a date/party dichotomy for hubs in protein interaction networks is not meaningful, and it might be more useful to conceive of roles for protein-protein interactions rather than for individual proteins.
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