VIVID: a web application for variant interpretation and visualisation in multidimensional analyses

Large-scale comparative genomics- and population genetic studies generate enormous amounts of polymorphism data in the form of DNA variants. Ultimately, the goal of many of these studies is to associate genetic variants to phenotypes or fitness. We introduce VIVID, an interactive, user-friendly web application that integrates a wide range of approaches for encoding genotypic to phenotypic information in any organism or disease, from an individual or population, in three-dimensional (3D) space. It allows mutation mapping and annotation, calculation of interactions and conservation scores, prediction of harmful effects, analysis of diversity and selection, and 3-dimensional (3D) visualisation of genotypic information encoded in Variant Call Format (VCF) on AlphaFold2 protein models. VIVID enables the rapid assessment of genes of interest in the study of adaptive evolution and the genetic load, and it helps prioritising targets for experimental validation. We demonstrate the utility of VIVID by exploring the evolutionary genetics of the parasitic protist Plasmodium falciparum, revealing geographic variation in the signature of balancing selection in potential targets of functional antibodies.

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The structure of weakly compressible grid-generated turbulence

Journal of Fluid Mechanics ◽

10.1017/s0022112000003402 ◽

2001 ◽

Vol 432 ◽

pp. 219-283 ◽

Cited By ~ 29

Author(s):

G. BRIASSULIS ◽

J. H. AGUI ◽

Y. ANDREOPOULOS

Keyword(s):

Mach Number ◽

Large Scale ◽

Isotropic Turbulence ◽

Three Dimensional ◽

High Amplitude ◽

Time Dependent ◽

Wide Range ◽

Dynamical Flow ◽

Set Up ◽

Decay Exponent

A decaying compressible nearly homogeneous and nearly isotropic grid-generated turbulent flow has been set up in a large scale shock tube research facility. Experiments have been performed using instrumentation with spatial resolution of the order of 7 to 26 Kolmogorov viscous length scales. A variety of turbulence-generating grids provided a wide range of turbulence scales with bulk flow Mach numbers ranging from 0.3 to 0.6 and turbulent Reynolds numbers up to 700. The decay of Mach number fluctuations was found to follow a power law similar to that describing the decay of incompressible isotropic turbulence. It was also found that the decay coefficient and the decay exponent decrease with increasing Mach number while the virtual origin increases with increasing Mach number. A possible mechanism responsible for these effects appears to be the inherently low growth rate of compressible shear layers emanating from the cylindrical rods of the grid. Measurements of the time-dependent, three dimensional vorticity vectors were attempted for the first time with a 12-wire miniature probe. This also allowed estimates of dilatation, compressible dissipation and dilatational stretching to be obtained. It was found that the fluctuations of these quantities increase with increasing mean Mach number of the flow. The time-dependent signals of enstrophy, vortex stretching/tilting vector and dilatational stretching vector were found to exhibit a rather strong intermittent behaviour which is characterized by high-amplitude bursts with values up to 8 times their r.m.s. within periods of less violent and longer lived events. Several of these bursts are evident in all the signals, suggesting the existence of a dynamical flow phenomenon as a common cause.

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Rapid 3D geological modeling to assess and visualize uncertainties in a web application

10.5194/egusphere-egu21-13187 ◽

2021 ◽

Author(s):

Daniel Pflieger ◽

Miguel de la Varga Hormazabal ◽

Simon Virgo ◽

Jan von Harten ◽

Florian Wellmann

Keyword(s):

Web Application ◽

High Performance ◽

Three Dimensional ◽

Cloud Services ◽

Management Approach ◽

Geological Modeling ◽

Web Browser ◽

3D Geological Modeling ◽

State Management ◽

Wide Range

Three dimensional modeling is a rapidly developing field in geological scientific and commercial applications. The combination of modeling and uncertainty analysis aides in understanding and quantitatively assessing complex subsurface structures. In recent years, many methods have been developed to facilitate this combined analysis, usually either through an extension of existing desktop applications or by making use of Jupyter notebooks as frontends. We evaluate here if modern web browser technology, linked to high-performance cloud services, can also be used for these types of analyses.For this purpose, we developed a web application as proof-of-concept with the aim to visualize three dimensional geological models provided by a server. The implementation enables the modification of input parameters with assigned probability distributions. This step enables the generation of randomized realizations of models and the quantification and visualization of propagated uncertainties. The software is implemented using HTML Web Components on the client side and a Python server, providing a RESTful API to the open source geological modeling tool &#8220;GemPy&#8221;. Encapsulating the main components in custom elements, in combination with a minimalistic state management approach and a template parser, allows for high modularity. This enables rapid extendibility of the functionality of the components depending on the user&#8217;s needs and an easy integration into existing web platforms.Our implementation shows that it is possible to extend and simplify modeling processes by creating an expandable web-based platform for probabilistic modeling, with the aim to increase the usability and to facilitate access to this functionality for a wide range of scientific analyses. The ability to compute models rapidly and with any given device in a web browser makes it flexible to use, and more accessible to a broader range of users.

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Electrooxidation enables highly regioselective dearomative annulation of indole and benzofuran derivatives

Nature Communications ◽

10.1038/s41467-019-13829-4 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 11

Author(s):

Kun Liu ◽

Wenxu Song ◽

Yuqi Deng ◽

Huiyue Yang ◽

Chunlan Song ◽

...

Keyword(s):

Large Scale ◽

Three Dimensional ◽

Thermal Conditions ◽

Kinetic Studies ◽

Added Value ◽

High Yield ◽

Paramagnetic Resonance ◽

Good Efficiency ◽

Rate Determining Step ◽

Wide Range

AbstractThe dearomatization of arenes represents a powerful synthetic methodology to provide three-dimensional chemicals of high added value. Here we report a general and practical protocol for regioselective dearomative annulation of indole and benzofuran derivatives in an electrochemical way. Under undivided electrolytic conditions, a series of highly functionalized five to eight-membered heterocycle-2,3-fused indolines and dihydrobenzofurans, which are typically unattainable under thermal conditions, can be successfully accessed in high yield with excellent regio- and stereo-selectivity. This transformation can also tolerate a wide range of functional groups and achieve good efficiency in large-scale synthesis under oxidant-free conditions. In addition, cyclic voltammetry, electron paramagnetic resonance (EPR) and kinetic studies indicate that the dehydrogenative dearomatization annulations arise from the anodic oxidation of indole into indole radical cation, and this process is the rate-determining step.

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A curated transcriptome dataset collection to investigate inborn errors of immunity

10.1101/526004 ◽

2019 ◽

Author(s):

Salim Bougarn ◽

Sabri Boughorbel ◽

Damien Chaussabel ◽

Nico Marr

Keyword(s):

Web Application ◽

Large Scale ◽

Mononuclear Cells ◽

Ex Vivo ◽

Clinical Manifestations ◽

Inherited Disorders ◽

Transcriptional Responses ◽

Control Subjects ◽

A Genome ◽

Wide Range

ABSTRACTPrimary immunodeficiencies (PIDs) are a heterogeneous group of inherited disorders, frequently caused by loss-of-function and less commonly by gain-of-function mutations, which can result in susceptibility to a broad or a very narrow range of infections but also in inflammatory, allergic or malignant diseases. Owing to the wide range in clinical manifestations and variability in penetrance and expressivity, there is an urgent need to better understand the underlying molecular, cellular and immunological phenotypes in PID patients in order to improve clinical diagnosis and management. Here we have compiled a manually curated collection of public transcriptome datasets mainly obtained from human whole blood, peripheral blood mononuclear cells (PBMCs) or fibroblasts of patients with PIDs and of control subjects for subsequent meta-analysis, query and interpretation. A total of nineteen (19) datasets derived from studies of PID patients were identified and retrieved from the NCBI Gene Expression Omnibus (GEO) database and loaded in GXB, a custom web application designed for interactive query and visualization of integrated large-scale data. The dataset collection includes samples from well characterized PID patients that were stimulated ex vivo under a variety of conditions to assess the molecular consequences of the underlying, naturally occurring gene defects on a genome-wide scale. Multiple sample groupings and rank lists were generated to facilitate comparisons of the transcriptional responses between different PID patients and control subjects. The GXB tool enables browsing of a single transcript across studies, thereby providing new perspectives on the role of a given molecule across biological systems and PID patients. This dataset collection is available at: http://pid.gxbsidra.org/dm3/geneBrowser/list.

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PinAPL-Py: A comprehensive web-application for the analysis of CRISPR/Cas9 screens

10.1101/147462 ◽

2017 ◽

Author(s):

Philipp N. Spahn ◽

Tyler Bath ◽

Ryan J. Weiss ◽

Jihoon Kim ◽

Jeffrey D. Esko ◽

...

Keyword(s):

Web Application ◽

Large Scale ◽

Sequencing Data ◽

Bioinformatic Tools ◽

Link Type ◽

Screening Experiments ◽

Independent Analysis ◽

Wide Range ◽

Set Up ◽

Sequence Quality

AbstractBackgroundLarge-scale genetic screens using CRISPR/Cas9 technology have emerged as a major tool for functional genomics. With its increased popularity, experimental biologists frequently acquire large sequencing datasets for which they often do not have an easy analysis option. While a few bioinformatic tools have been developed for this purpose, their utility is still hindered either due to limited functionality or the requirement of bioinformatic expertise.ResultsTo make sequencing data analysis of CRISPR/Cas9 screens more accessible to a wide range of scientists, we developed a Platform-independent Analysis of Pooled Screens using Python (PinAPL-Py), which is operated as an intuitive web-service. PinAPL-Py implements state-of-the-art tools and statistical models, assembled in a comprehensive workflow covering sequence quality control, automated sgRNA sequence extraction, alignment, sgRNA enrichment/depletion analysis and gene ranking. The workflow is set up to use a variety of popular sgRNA libraries as well as custom libraries that can be easily uploaded. Various analysis options are offered, suitable to analyze a large variety of CRISPR/Cas9 screening experiments. Analysis output includes ranked lists of sgRNAs and genes, and publication-ready plots.ConclusionsPinAPL-Py helps to advance genome-wide screening efforts by combining comprehensive functionality with user-friendly implementation. PinAPL-Py is freely accessible at http://pinapl-py.ucsd.edu with instructions, documentation and test datasets. The source code is available at https://github.com/LewisLabUCSD/PinAPL-Py

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Validation of a Finite Element Toolbox for Studying Flaw Interaction

Volume 6: Materials and Fabrication ◽

10.1115/pvp2020-21274 ◽

2020 ◽

Author(s):

Harry E. Coules

Keyword(s):

Finite Element ◽

Fracture Mechanics ◽

Large Scale ◽

Structural Integrity ◽

Three Dimensional ◽

Integrity Assessment ◽

Linear Elastic ◽

Wide Range ◽

Parametric Studies ◽

Elastic Crack

Abstract Structural integrity assessment often requires the interaction of multiple closely-spaced cracks or flaws in a structure to be considered. Although many procedures for structural integrity assessment include rules for determining the significance of flaw interaction, and for re-characterising interacting flaws, these rules can be difficult to validate in a fracture mechanics framework. int_defects is an open-source MATLAB toolbox which uses the Abaqus finite element suite to perform large-scale parametric studies in cracked-body analysis. It is designed to allow developers of assessment codes to check the accuracy of simplified interaction criteria under a wide range of conditions, e.g. for different interacting flaw geometries, material models and loading cases. int_defects can help analysts perform parametric studies to determine linear elastic crack tip stress field parameters, elastic-plastic parameters and plastic limit loads for simple three-dimensional cracked bodies relevant to assessment codes. This article focusses on the validation of int_defects using existing fracture mechanics results. Through a set of validation examples, int_defects is shown to produce accurate results for a very wide range of cases in both linear and non-linear cracked-body analysis. Nevertheless, it is emphasised that users of this software should be conscious of the inherent limitations of LEFM and EPFM theory when applied to real fracture processes, and effects such as constraint loss should be considered when formulating interaction criteria.

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Tourism demonstration system for large-scale museums based on 3D virtual simulation technology

The Electronic Library ◽

10.1108/el-08-2019-0185 ◽

2020 ◽

Vol 38 (2) ◽

pp. 367-381

Author(s):

Yongcai Hu ◽

Wei Sun ◽

Xigang Liu ◽

Quan Gan ◽

Jie Shi

Keyword(s):

Large Scale ◽

Three Dimensional ◽

Virtual Simulation ◽

Simulation Technology ◽

Large Space ◽

Content Type ◽

3D Network ◽

Wide Range ◽

3D Scene

Purpose The purpose of this study is to enhance audience experience in museum by using three-dimensional (3D) virtual simulation technology. Design/methodology/approach In this study, a large space museum building tourism demonstration system based on 3D virtual simulation technology was proposed. Starting from the concept of virtual reality (VR), the characteristics of VR and the classification of VR systems were introduced, and the research status of VR technology at home and abroad and the application of 3D virtual simulation were discussed. Then the key technologies of 3D modeling, 3D scene optimization and 3D simulation driving of 3D virtual simulation were expounded, and the characteristics and application scope of different technical methods were analyzed. Finally, an example of the Hongzhou Kiln 3D network museum was listed. Findings The research results showed that 3D virtual simulation has a wide range of applications in the field of VR. Different elements need to be considered for different types of applications, and different contents need to be integrated to achieve the corresponding interaction modes. Originality/value Virtual image; multimedia; large space museum; tourism demonstration system; 3D virtual simulation technology.

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Turbulent 2.5-dimensional dynamos

Journal of Fluid Mechanics ◽

10.1017/jfm.2016.366 ◽

2016 ◽

Vol 799 ◽

pp. 246-264 ◽

Cited By ~ 4

Author(s):

K. Seshasayanan ◽

A. Alexakis

Keyword(s):

Turbulent Flows ◽

Large Scale ◽

Stokes Equations ◽

Three Dimensional ◽

Reynolds Numbers ◽

Navier Stokes ◽

Two Dimensional ◽

Navier Stokes Equations ◽

Wide Range ◽

Two Dimensional Flow

We study the linear stage of the dynamo instability of a turbulent two-dimensional flow with three components $(u(x,y,t),v(x,y,t),w(x,y,t))$ that is sometimes referred to as a 2.5-dimensional (2.5-D) flow. The flow evolves based on the two-dimensional Navier–Stokes equations in the presence of a large-scale drag force that leads to the steady state of a turbulent inverse cascade. These flows provide an approximation to very fast rotating flows often observed in nature. The low dimensionality of the system allows for the realization of a large number of numerical simulations and thus the investigation of a wide range of fluid Reynolds numbers $Re$, magnetic Reynolds numbers $Rm$ and forcing length scales. This allows for the examination of dynamo properties at different limits that cannot be achieved with three-dimensional simulations. We examine dynamos for both large and small magnetic Prandtl-number turbulent flows $Pm=Rm/Re$, close to and away from the dynamo onset, as well as dynamos in the presence of scale separation. In particular, we determine the properties of the dynamo onset as a function of $Re$ and the asymptotic behaviour in the large $Rm$ limit. We are thus able to give a complete description of the dynamo properties of these turbulent 2.5-D flows.

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Large-scale dynamics in turbulent mixing and the three-dimensional space–time behaviour of outer fluid interfaces

Journal of Fluid Mechanics ◽

10.1017/s0022112002002240 ◽

2002 ◽

Vol 471 ◽

pp. 381-408 ◽

Cited By ~ 19

Author(s):

HARIS J. CATRAKIS ◽

ROBERTO C. AGUIRRE ◽

JESUS RUIZ-PLANCARTE ◽

ROBERT D. THAYNE ◽

BRENDA A. McDONALD ◽

...

Keyword(s):

Large Scale ◽

Dimensional Space ◽

Three Dimensional ◽

Space Time ◽

Mixing Efficiency ◽

Fluid Interfaces ◽

Ambient Fluid ◽

Wide Range ◽

Dimensional Space Time ◽

Three Dimensional Space

Experiments have been conducted to investigate turbulent mixing and the dynamics of outer fluid interfaces, i.e. the interfaces between mixed fluid and pure ambient fluid. A novel six-foot-diameter octagonal-tank flow facility was developed to enable the optical imaging of fluid interfaces above the mixing transition, corresponding to fully developed turbulence. Approximately 10003 whole-field three-dimensional space– time measurements of the concentration field were recorded using laser-induced- fluorescence digital-imaging techniques in turbulent jets at a Reynolds number of Re ∼ 20 000, Schmidt number of Sc ∼ 2000, and downstream distance of ∼ 500 nozzle diameters. Multiple large-scale regions of spatially nearly uniform-concentration fluid are evident in instantaneous visualizations, in agreement with previous findings above the mixing transition. The ensemble-averaged probability density function of concentration is found to exhibit linear dependence over a wide range of concentration thresholds. This can be accounted for in terms of the dynamics of large-scale well- mixed regions. Visualization of the three-dimensional space–time concentration field indicates that molecular mixing of entrained pure ambient fluid is dynamically initiated and accomplished in the vicinity of the unsteady large scales. Examination of the outer interfaces shows that they are dynamically confined primarily near the instantaneous large-scale boundaries of the flow. This behaviour is quantified in terms of the probability density of the location of the outer interfaces relative to the flow centreline and the probability of pure ambient fluid as a function of distance from the centreline. The current measurements show that the dynamics of outer interfaces above the mixing transition is significantly different from the behaviour below the transition, where previous studies have shown that unmixed ambient fluid can extend across a wide range of transverse locations in the flow interior. The present observations of dynamical confinement of the outer interfaces to the unsteady large scales, and considerations of entrainment, suggest that the mechanism responsible for this behaviour must be the coupling of large-scale flow dynamics with the presence of small-scale structures internal to the large-scale structures, above the mixing transition. The dynamics and structure of the outer interfaces across the entire range of space–time scales are quantified in terms of a distribution of generalized level-crossing scales. The outer-interface behaviour determines the mixing efficiency of the flow, i.e. fraction of mixed fluid. The present findings indicate that the large-scale dynamics of the outer interfaces above the mixing transition provides the dominant contribution to the mixing efficiency. This suggests a new way to quantify the mixing efficiency of turbulent flows at high Reynolds numbers.

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FMM/GPU Accelerated BEM Simulations of Emulsion Flow in Microchannels

Volume 7B: Fluids Engineering Systems and Technologies ◽

10.1115/imece2013-63193 ◽

2013 ◽

Cited By ~ 2

Author(s):

Olga A. Abramova ◽

Yulia A. Itkulova ◽

Nail A. Gumerov

Keyword(s):

Oil Recovery ◽

Large Scale ◽

Heterogeneous Computing ◽

Three Dimensional ◽

Industrial Applications ◽

Computational Techniques ◽

Graphics Processors ◽

Two Phase ◽

Scalable Algorithm ◽

Wide Range

Modeling of motion of two-phase liquids in microchannels of different shape is needed for a variety of industrial applications, such as enhanced oil recovery, advanced material processing, and biotechnology. Development of efficient computational techniques is required for understanding the mechanisms of many effects in “liquid-liquid” systems, such as the jamming of emulsion flows in microchannels and blood cell motion in capillaries. In the present study, a mathematical model of a three-dimensional flow of a mixture of two Newtonian liquids of a droplet structure in microchannels at low Reynold’s numbers is considered. The computational approach is based on the boundary element method accelerated both via an advanced scalable algorithm (FMM), and via utilization of a heterogeneous computing architecture (multicore CPUs and graphics processors). To solve large scale problems flexible GMRES solver is developed. Example computations are conducted for dynamics of many deformable drops of different sizes in microchannels. The results of simulations and accuracy/performance of the method are discussed. The developed approach can be used for solution of a wide range of problems related to emulsion flows in micro- and nanoscales.

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