scholarly journals Dimension-reduction simplifies the analysis of signal crosstalk in a bacterial quorum sensing pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Taylor Miller ◽  
Keval Patel ◽  
Coralis Rodriguez ◽  
Eric V. Stabb ◽  
Stephen J. Hagen
Keyword(s):  
Dimension Reduction ◽  
Vibrio Fischeri ◽  
Individual Cell ◽  
Full Range ◽  
Homoserine Lactone ◽  
Tuning Parameter ◽  
Statistical Distributions ◽  
Cell Responses ◽  
Low Dimensional ◽  
Signal Crosstalk

AbstractMany pheromone sensing bacteria produce and detect more than one chemically distinct signal, or autoinducer. The pathways that detect these signals are typically noisy and interlocked through crosstalk and feedback. As a result, the sensing response of individual cells is described by statistical distributions that change under different combinations of signal inputs. Here we examine how signal crosstalk reshapes this response. We measure how combinations of two homoserine lactone (HSL) input signals alter the statistical distributions of individual cell responses in the AinS/R- and LuxI/R-controlled branches of the Vibrio fischeri bioluminescence pathway. We find that, while the distributions of pathway activation in individual cells vary in complex fashion with environmental conditions, these changes have a low-dimensional representation. For both the AinS/R and LuxI/R branches, the distribution of individual cell responses to mixtures of the two HSLs is effectively one-dimensional, so that a single tuning parameter can capture the full range of variability in the distributions. Combinations of crosstalking HSL signals extend the range of responses for each branch of the circuit, so that signals in combination allow population-wide distributions that are not available under a single HSL input. Dimension reduction also simplifies the problem of identifying the HSL conditions to which the pathways and their outputs are most sensitive. A comparison of the maximum sensitivity HSL conditions to actual HSL levels measured during culture growth indicates that the AinS/R and LuxI/R branches lack sensitivity to population density except during the very earliest and latest stages of growth respectively.

scholarly journals Local dimension reduction of summary statistics for likelihood-free inference

2019 ◽  
Vol 30 (3) ◽  
pp. 559-570
Author(s):  
Jukka Sirén ◽  
Samuel Kaski
Keyword(s):  
Dimension Reduction ◽  
Estimation Accuracy ◽  
Summary Statistics ◽  
Functional Relationships ◽  
Reduction Techniques ◽  
Space Localization ◽  
Reliable Performance ◽  
Whole Space ◽  
Approximate Bayesian ◽  
Low Dimensional

Abstract Approximate Bayesian computation (ABC) and other likelihood-free inference methods have gained popularity in the last decade, as they allow rigorous statistical inference for complex models without analytically tractable likelihood functions. A key component for accurate inference with ABC is the choice of summary statistics, which summarize the information in the data, but at the same time should be low-dimensional for efficiency. Several dimension reduction techniques have been introduced to automatically construct informative and low-dimensional summaries from a possibly large pool of candidate summaries. Projection-based methods, which are based on learning simple functional relationships from the summaries to parameters, are widely used and usually perform well, but might fail when the assumptions behind the transformation are not satisfied. We introduce a localization strategy for any projection-based dimension reduction method, in which the transformation is estimated in the neighborhood of the observed data instead of the whole space. Localization strategies have been suggested before, but the performance of the transformed summaries outside the local neighborhood has not been guaranteed. In our localization approach the transformation is validated and optimized over validation datasets, ensuring reliable performance. We demonstrate the improvement in the estimation accuracy for localized versions of linear regression and partial least squares, for three different models of varying complexity.

scholarly journals On coherent structure in wall turbulence

2013 ◽  
Vol 728 ◽  
pp. 196-238 ◽  
Author(s):  
A. S. Sharma ◽  
B. J. McKeon
Keyword(s):  
Turbulent Flow ◽  
Coherent Structure ◽  
Stokes Equations ◽  
Travelling Waves ◽  
Full Range ◽  
Wall Turbulence ◽  
Critical Layer ◽  
Taylor’S Hypothesis ◽  
Response Modes ◽  
Low Dimensional

AbstractA new theory of coherent structure in wall turbulence is presented. The theory is the first to predict packets of hairpin vortices and other structure in turbulence, and their dynamics, based on an analysis of the Navier–Stokes equations, under an assumption of a turbulent mean profile. The assumption of the turbulent mean acts as a restriction on the class of possible structures. It is shown that the coherent structure is a manifestation of essentially low-dimensional flow dynamics, arising from a critical-layer mechanism. Using the decomposition presented in McKeon & Sharma (J. Fluid Mech., vol. 658, 2010, pp. 336–382), complex coherent structure is recreated from minimal superpositions of response modes predicted by the analysis, which take the form of radially varying travelling waves. The leading modes effectively constitute a low-dimensional description of the turbulent flow, which is optimal in the sense of describing the resonant effects around the critical layer and which minimally predicts all types of structure. The approach is general for the full range of scales. By way of example, simple combinations of these modes are offered that predict hairpins and modulated hairpin packets. The example combinations are chosen to represent observed structure, consistent with the nonlinear triadic interaction for wavenumbers that is required for self-interaction of structures. The combination of the three leading response modes at streamwise wavenumbers $6, ~1, ~7$ and spanwise wavenumbers $\pm 6, ~\pm 6, ~\pm 12$, respectively, with phase velocity $2/ 3$, is understood to represent a turbulence ‘kernel’, which, it is proposed, constitutes a self-exciting process analogous to the near-wall cycle. Together, these interactions explain how the mode combinations may self-organize and self-sustain to produce experimentally observed structure. The phase interaction also leads to insight into skewness and correlation results known in the literature. It is also shown that the very large-scale motions act to organize hairpin-like structures such that they co-locate with areas of low streamwise momentum, by a mechanism of locally altering the shear profile. These energetic streamwise structures arise naturally from the resolvent analysis, rather than by a summation of hairpin packets. In addition, these packets are modulated through a ‘beat’ effect. The relationship between Taylor’s hypothesis and coherence is discussed, and both are shown to be the consequence of the localization of the response modes around the critical layer. A pleasing link is made to the classical laminar inviscid theory, whereby the essential mechanism underlying the hairpin vortex is captured by two obliquely interacting Kelvin–Stuart (cat’s eye) vortices. Evidence for the theory is presented based on comparison with observations of structure in turbulent flow reported in the experimental and numerical simulation literature and with exact solutions reported in the transitional literature.

scholarly journals Novel Reporter for Identification of Interference with Acyl Homoserine Lactone and Autoinducer-2 Quorum Sensing

2014 ◽  
Vol 81 (4) ◽  
pp. 1477-1489 ◽  
Author(s):  
Nancy Weiland-Bräuer ◽  
Nicole Pinnow ◽  
Ruth A. Schmitz
Keyword(s):  
Quorum Sensing ◽  
Vibrio Fischeri ◽  
Quorum Quenching ◽  
Homoserine Lactone ◽  
Signal Molecules ◽  
Lethal Gene ◽  
Reporter Strain ◽  
Content Type ◽  
E Coli ◽  
Autoinducer 2

ABSTRACTTwo reporter strains were established to identify novel biomolecules interfering with bacterial communication (quorum sensing [QS]). The basic design of theseEscherichia coli-based systems comprises a gene encoding a lethal protein fused to promoters induced in the presence of QS signal molecules. Consequently, theseE. colistrains are unable to grow in the presence of the respective QS signal molecules unless a nontoxic QS-interfering compound is present. The first reporter strain designed to detect autoinducer-2 (AI-2)-interfering activities (AI2-QQ.1) contained theE. coliccdBlethal gene under the control of theE. colilsrApromoter. The second reporter strain (AI1-QQ.1) contained theVibrio fischeriluxIpromoter fused to theccdBgene to detect interference with acyl-homoserine lactones. Bacteria isolated from the surfaces of several marine eukarya were screened for quorum-quenching (QQ) activities using the established reporter systems AI1-QQ.1 and AI2-QQ.1. Out of 34 isolates, two interfered with acylated homoserine lactone (AHL) signaling, five interfered with AI-2 QS signaling, and 10 were demonstrated to interfere with both signal molecules. Open reading frames (ORFs) conferring QQ activity were identified for three selected isolates (Photobacteriumsp.,Pseudoalteromonassp., andVibrio parahaemolyticus). Evaluation of the respective heterologously expressed and purified QQ proteins confirmed their ability to interfere with the AHL and AI-2 signaling processes.

scholarly journals Reversible Acyl-Homoserine Lactone Binding to Purified Vibrio fischeri LuxR Protein

2004 ◽  
Vol 186 (3) ◽  
pp. 631-637 ◽  
Author(s):  
M. L. Urbanowski ◽  
C. P. Lostroh ◽  
E. P. Greenberg
Keyword(s):  
Quorum Sensing ◽  
Promoter Region ◽  
Vibrio Fischeri ◽  
Homoserine Lactone ◽  
Acyl Homoserine Lactone ◽  
E Coli ◽  
High Affinity ◽  
Founding Member ◽  
Luxr Homolog

ABSTRACT The Vibrio fischeri LuxR protein is the founding member of a family of acyl-homoserine lactone-responsive quorum-sensing transcription factors. Previous genetic evidence indicates that in the presence of its quorum-sensing signal, N-(3-oxohexanoyl) homoserine lactone (3OC6-HSL), LuxR binds to lux box DNA within the promoter region of the luxI gene and activates transcription of the luxICDABEG luminescence operon. We have purified LuxR from recombinant Escherichia coli. Purified LuxR binds specifically and with high affinity to DNA containing a lux box. This binding requires addition of 3OC6-HSL to the assay reactions, presumably forming a LuxR-3OC6-HSL complex. When bound to the lux box at the luxI promoter in vitro, LuxR-3OC6-HSL enables E. coli RNA polymerase to initiate transcription from the luxI promoter. Unlike the well-characterized LuxR homolog TraR in complex with its signal (3-oxo-octanoyl-HSL), the LuxR-30C6-HSL complex can be reversibly inactivated by dilution, suggesting that 3OC6-HSL in the complex is not tightly bound and is in equilibrium with the bulk solvent. Thus, although LuxR and TraR both bind 3-oxoacyl-HSLs, the binding is qualitatively different. The differences have implications for the ways in which these proteins respond to decreases in signal concentrations or rapid drops in population density.

Contribution of rod, on-bipolar, and horizontal cell light responses to the ERG of dogfish retina

1999 ◽  
Vol 16 (3) ◽  
pp. 503-511 ◽  
Author(s):  
R.A. SHIELLS ◽  
G. FALK
Keyword(s):  
Bipolar Cell ◽  
Time Course ◽  
Horizontal Cell ◽  
Full Range ◽  
Bipolar Cells ◽  
Horizontal Cells ◽  
Negative Wave ◽  
Low Light ◽  
Cell Responses ◽  
Light Intensities

Simultaneous extracellular ERG and intracellular recordings from horizontal and ON-bipolar cells were obtained from the dark-adapted retina of the dogfish. The light intensity–peak response relation (IR) and time course of on-bipolar cell responses closely resembled that of the ERG b-wave, but only at low light intensities [<10 rhodopsin molecules bleached per rod (Rh*)]. Block of on-bipolar cell responses with 50 μM 2-amino-4-phosphonobutyrate (APB) abolished the b-wave and unmasked a vitreal-negative wave. Subtraction from the control ERG resulted in the isolation of a vitreal-positive ERG with an IR which matched that of on-bipolar cells over the full range of light intensities. The D.C. component of the ERG arises as a result of sustained depolarization of on-bipolar cells in response to long (>0.5 s) dim light stimuli, or following bright light flashes. The IR of horizontal cells and the vitreal-negative wave unmasked by APB could be matched by scaling at low light intensities (<5 Rh*). However, horizontal cell responses saturated at about 30 Rh*, while the vitreal-negative wave continued to increase in amplitude. The time course of horizontal cell membrane current with dim flashes could be matched to the rising phase of the vitreal-negative wave, assuming that the delay in generating the voltage response in horizontal cells is due to their long (100 ms) membrane time constant. Blocking post-photoreceptor activity resulted in a much smaller vitreal-negative wave than that unmasked by APB alone. We conclude that the b-wave arises from on-bipolar cell depolarization, while the leading edge of the a-wave is a composite of the change in extracellular voltage drop across the rod layer and a component (proximal PIII) reflecting a decrease in extracellular K+ as horizontal cell synaptic channels close with light.

scholarly journals LuxR- and Acyl-Homoserine-Lactone-Controlled Non-luxGenes Define a Quorum-Sensing Regulon in Vibrio fischeri

2000 ◽  
Vol 182 (10) ◽  
pp. 2811-2822 ◽  
Author(s):  
Sean M. Callahan ◽  
Paul V. Dunlap
Keyword(s):  
Quorum Sensing ◽  
Population Density ◽  
Vibrio Fischeri ◽  
Polyacrylamide Gel Electrophoresis ◽  
Symbiotic Bacterium ◽  
Homoserine Lactone ◽  
Acyl Homoserine Lactone ◽  
Protein Patterns ◽  
Promoter Regions ◽  
Key Enzyme

ABSTRACT The luminescence (lux) operon (luxICDABEG) of the symbiotic bacterium Vibrio fischeri is regulated by the transcriptional activator LuxR and two acyl-homoserine lactone (acyl-HSL) autoinducers (the luxI-dependent 3-oxo-hexanoyl-HSL [3-oxo-C6-HSL] and the ainS-dependent octanoyl-HSL [C8-HSL]) in a population density-responsive manner called quorum sensing. To identify quorum-sensing-regulated (QSR) proteins different from those encoded by lux genes, we examined the protein patterns of V. fischeri quorum-sensing mutants defective in luxI, ainS, andluxR by two-dimensional polyacrylamide gel electrophoresis. Five non-Lux QSR proteins, QsrP, RibB, AcfA, QsrV, and QSR 7, were identified; their production occurred preferentially at high population density, required both LuxR and 3-oxo-C6-HSL, and was inhibited by C8-HSL at low population density. The genes encoding two of the QSR proteins were characterized: qsrP directs cells to synthesize an apparently novel periplasmic protein, andribB is a homolog of the Escherichia coli gene for 3,4-dihydroxy-2-butanone 4-phosphate synthase, a key enzyme for riboflavin synthesis. The qsrP and ribBpromoter regions each contained a sequence similar to thelux operon lux box, a 20-bp region of dyad symmetry necessary for LuxR/3-oxo-C6-HSL-dependent activation oflux operon transcription. V. fischeri qsrP andribB mutants exhibited no distinct phenotype in culture. However, a qsrP mutant, in competition with its parent strain, was less successful in colonizing Euprymna scolopes, the symbiotic host of V. fischeri. The newly identified QSR genes, together with the lux operon, define a LuxR/acyl-HSL-responsive quorum-sensing regulon in V. fischeri.

scholarly journals AinS Quorum Sensing Regulates the Vibrio fischeri Acetate Switch

2008 ◽  
Vol 190 (17) ◽  
pp. 5915-5923 ◽  
Author(s):  
Sarah V. Studer ◽  
Mark J. Mandel ◽  
Edward G. Ruby
Keyword(s):  
Quorum Sensing ◽  
Vibrio Fischeri ◽  
Growth Yield ◽  
Normal Growth ◽  
Homoserine Lactone ◽  
Acetate Metabolism ◽  
Wild Type ◽  
Gene Encoding ◽  
Sensing Systems ◽  
Acetate Utilization

ABSTRACT The marine bacterium Vibrio fischeri uses two acyl-homoserine lactone (acyl-HSL) quorum-sensing systems. The earlier signal, octanoyl-HSL, produced by AinS, is required for normal colonization of the squid Euprymna scolopes and, in culture, is necessary for a normal growth yield. In examining the latter requirement, we found that during growth in a glycerol/tryptone-based medium, wild-type V. fischeri cells initially excrete acetate but, in a metabolic shift termed the acetate switch, they subsequently utilize the acetate, removing it from the medium. In contrast, an ainS mutant strain grown in this medium does not remove the excreted acetate, which accumulates to lethal levels. The acetate switch is characterized by the induction of acs, the gene encoding acetyl coenzyme A (acetyl-CoA) synthetase, leading to uptake of the excreted acetate. Wild-type cells induce an acs transcriptional reporter 25-fold, coincident with the disappearance of the extracellular acetate; in contrast, the ainS mutant did not display significant induction of the acs reporter. Supplementation of the medium of an ainS mutant with octanoyl-HSL restored normal levels of acs induction and acetate uptake. Additional mutant analyses indicated that acs regulation was accomplished through the regulator LitR but was independent of the LuxIR quorum-signaling pathway. Importantly, the acs mutant of V. fischeri has a competitive defect when colonizing the squid, indicating the importance of proper control of acetate metabolism in the light of organ symbiosis. This is the first report of quorum-sensing control of the acetate switch, and it indicates a metabolic connection between acetate utilization and cell density.

scholarly journals Blade Envelopes Part I: Concept and Methodology

2021 ◽  
pp. 1-24
Author(s):  
Chun Yui Wong ◽  
Pranay Seshadri ◽  
Ashley Scillitoe ◽  
Andrew Duncan ◽  
Geoffrey T. Parks
Keyword(s):  
Boundary Layer ◽  
Dimension Reduction ◽  
Performance Metrics ◽  
Aerodynamic Performance ◽  
Rules Of Thumb ◽  
Manufacturing Tolerances ◽  
Service Degradation ◽  
Computational Methodology ◽  
Low Dimensional ◽  
Single Objective

Abstract Blades manufactured through flank and point milling will likely exhibit geometric variability. Gauging the aerodynamic repercussions of such variability, prior to manufacturing a component, is challenging enough, let alone trying to predict what the amplified impact of any in-service degradation will be. While rules of thumb that govern the tolerance band can be devised based on expected boundary layer characteristics at known regions and levels of degradation, it remains a challenge to translate these insights into quantitative bounds for manufacturing. In this work, we tackle this challenge by leveraging ideas from dimension reduction to construct low-dimensional representations of aerodynamic performance metrics. These low-dimensional models can identify a subspace which contains designs that are invariant in performance -- the inactive subspace. By sampling within this subspace, we design techniques for drafting manufacturing tolerances and for quantifying whether a scanned component should be used or scrapped. We introduce the blade envelope as a computational manufacturing guide for a blade. In this paper, the first of two parts, we discuss its underlying concept and detail its computational methodology, assuming one is interested only in the single objective of ensuring that the loss of all manufactured blades remains constant. To demonstrate the utility of our ideas we devise a series of computational experiments with the Von Karman Institute's LS89 turbine blade.

scholarly journals Dictionary learning allows model-free pseudotime estimation of transcriptomic data

BMC Genomics ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Mona Rams ◽  
Tim O.F. Conrad
Keyword(s):  
Dimension Reduction ◽  
Dictionary Learning ◽  
Real World ◽  
Estimation Methods ◽  
Dynamic Processes ◽  
Dimensional Representation ◽  
Transcriptomic Data ◽  
Model Free ◽  
Real World Datasets ◽  
Low Dimensional

Abstract Background Pseudotime estimation from dynamic single-cell transcriptomic data enables characterisation and understanding of the underlying processes, for example developmental processes. Various pseudotime estimation methods have been proposed during the last years. Typically, these methods start with a dimension reduction step because the low-dimensional representation is usually easier to analyse. Approaches such as PCA, ICA or t-SNE belong to the most widely used methods for dimension reduction in pseudotime estimation methods. However, these methods usually make assumptions on the derived dimensions, which can result in important dataset properties being missed. In this paper, we suggest a new dictionary learning based approach, dynDLT, for dimension reduction and pseudotime estimation of dynamic transcriptomic data. Dictionary learning is a matrix factorisation approach that does not restrict the dependence of the derived dimensions. To evaluate the performance, we conduct a large simulation study and analyse 8 real-world datasets. Results The simulation studies reveal that firstly, dynDLT preserves the simulated patterns in low-dimension and the pseudotimes can be derived from the low-dimensional representation. Secondly, the results show that dynDLT is suitable for the detection of genes exhibiting the simulated dynamic patterns, thereby facilitating the interpretation of the compressed representation and thus the dynamic processes. For the real-world data analysis, we select datasets with samples that are taken at different time points throughout an experiment. The pseudotimes found by dynDLT have high correlations with the experimental times. We compare the results to other approaches used in pseudotime estimation, or those that are method-wise closely connected to dictionary learning: ICA, NMF, PCA, t-SNE, and UMAP. DynDLT has the best overall performance for the simulated and real-world datasets. Conclusions We introduce dynDLT, a method that is suitable for pseudotime estimation. Its main advantages are: (1) It presents a model-free approach, meaning that it does not restrict the dependence of the derived dimensions; (2) Genes that are relevant in the detected dynamic processes can be identified from the dictionary matrix; (3) By a restriction of the dictionary entries to positive values, the dictionary atoms are highly interpretable.

scholarly journals EVALUATING UNIFORM MANIFOLD APPROXIMATION AND PROJECTION FOR DIMENSION REDUCTION AND VISUALIZATION OF POLINSAR FEATURES

2021 ◽  
Vol V-1-2021 ◽  
pp. 39-46
Author(s):  
S. Schmitz ◽  
U. Weidner ◽  
H. Hammer ◽  
A. Thiele
Keyword(s):  
Dimension Reduction ◽  
Visual Analysis ◽  
Principal Component ◽  
Feature Space ◽  
Decomposition Methods ◽  
High Dimensional ◽  
Feature Representations ◽  
Wide Range ◽  
Nonlinear Dimension ◽  
Low Dimensional

Abstract. In this paper, the nonlinear dimension reduction algorithm Uniform Manifold Approximation and Projection (UMAP) is investigated to visualize information contained in high dimensional feature representations of Polarimetric Interferometric Synthetic Aperture Radar (PolInSAR) data. Based on polarimetric parameters, target decomposition methods and interferometric coherences a wide range of features is extracted that spans the high dimensional feature space. UMAP is applied to determine a representation of the data in 2D and 3D euclidean space, preserving local and global structures of the data and still suited for classification. The performance of UMAP in terms of generating expressive visualizations is evaluated on PolInSAR data acquired by the F-SAR sensor and compared to that of Principal Component Analysis (PCA), Laplacian Eigenmaps (LE) and t-distributed Stochastic Neighbor embedding (t-SNE). For this purpose, a visual analysis of 2D embeddings is performed. In addition, a quantitative analysis is provided for evaluating the preservation of information in low dimensional representations with respect to separability of different land cover classes. The results show that UMAP exceeds the capability of PCA and LE in these regards and is competitive with t-SNE.

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