Interactive Browsing Research Articles

Neuronal wiring diagram of an adult brain

Connections between neurons can be mapped by acquiring and analysing electron microscopic brain images. In recent years, this approach has been applied to chunks of brains to reconstruct local connectivity maps that are highly informative1–6, but nevertheless inadequate for understanding brain function more globally. Here we present a neuronal wiring diagram of a whole brain containing 5 × 107 chemical synapses7 between 139,255 neurons reconstructed from an adult female Drosophila melanogaster8,9. The resource also incorporates annotations of cell classes and types, nerves, hemilineages and predictions of neurotransmitter identities10–12. Data products are available for download, programmatic access and interactive browsing and have been made interoperable with other fly data resources. We derive a projectome—a map of projections between regions—from the connectome and report on tracing of synaptic pathways and the analysis of information flow from inputs (sensory and ascending neurons) to outputs (motor, endocrine and descending neurons) across both hemispheres and between the central brain and the optic lobes. Tracing from a subset of photoreceptors to descending motor pathways illustrates how structure can uncover putative circuit mechanisms underlying sensorimotor behaviours. The technologies and open ecosystem reported here set the stage for future large-scale connectome projects in other species.

PerturbAtlas: a comprehensive atlas of public genetic perturbation bulk RNA-seq datasets.

Manipulating gene expression is crucial for understanding gene function, with high-throughput sequencing techniques such as RNA-seq elucidating the downstream mechanisms involved. However, the lack of a standardized metadata format for small-scale perturbation expression datasets in public repositories hinders their reuse. To address this issue, we developed PerturbAtlas, an add-value resource that re-analyzes publicly archived RNA-seq libraries to provide quantitative data on gene expression, transcript profiles, and alternative splicing events following genetic perturbation. PerturbAtlas assists users in identifying trends at the gene and isoform levels in perturbation assays by re-analyzing a curated set of 122801 RNA-seq libraries across 13 species. This resource is freely available at https://perturbatlas.kratoss.site as both raw data tables and an interactive browser, allowing searches by species, tissueor genomic features. The results provide detailed information on alterations following perturbations, accessible through both forward and reverse approaches, thereby enabling the exploration of perturbation consequences and the identification of potential causal perturbations.

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance. Genes encoding ion channels show strong association with multiple epilepsy subtypes, including epileptic encephalopathies, generalized and focal epilepsies, while most other gene discoveries are subtype-specific, highlighting distinct genetic contributions to different epilepsies. Combining results from rare single nucleotide/short indel-, copy number-, and common variants, we offer an expanded view of the genetic architecture of epilepsy, with growing evidence of convergence among different genetic risk loci on the same genes. Top candidate genes are enriched for roles in synaptic transmission and neuronal excitability, particularly postnatally and in the neocortex. We also identify shared rare variant risk between epilepsy and other neurodevelopmental disorders. Our data can be accessed via an interactive browser, hopefully facilitating diagnostic efforts and accelerating the development of follow-up studies.

NeoTCR: an immunoinformatic database of experimentally-supported functional neoantigen-specific TCR sequences.

Neoantigen-based immunotherapy has demonstrated long-lasting antitumor activity. The recognition of neoantigens by T cell receptors (TCRs) is considered a trigger for antitumor responses. Due to the overwhelming number of TCR repertoires in the human genome, pinpointing neoantigen-specific TCRs is a formidable challenge. Recent studies have identified a number of functional neoantigen-specific TCRs, but the corresponding information is scattered across published literature and is difficult to retrieve. To improve access to these data, we developed an immunoinformatic database (NeoTCR) containing a unified description of publicly available neoantigen-specific TCR sequences, as well as relevant information on targeted neoantigens, from experimentally supported studies across 18 cancer subtypes. A user-friendly web interface allows interactive browsing and running of complex database queries. To facilitate rapid identification of neoantigen-specific TCRs from raw sequencing data, NeoTCR offers a one-stop analysis for annotation and visualization of TCR clonotypes, discovery of existing neoantigen-specific TCRs, and exclusion of bystander viral-associated TCRs. NeoTCR represents a unique tool to expedite future studies of neoantigen-specific TCRs and the development of neoantigen-based immunotherapy. NeoTCR is available at http://neotcrdb.bioaimed.com/ and https://github.com/lyotvincent/NeoTCR.

HiBrowser: an interactive and dynamic browser for synchronous Hi-C data visualization.

With the development of chromosome conformation capture technology, the genome-wide investigation of higher-order chromatin structure by using high-throughput chromatin conformation capture (Hi-C) technology is emerging as an important component for understanding the mechanism of gene regulation. Considering genetic and epigenetic differences are typically used to explore the pathological reasons on the chromosome and gene level, visualizing multi-omics data and performing an intuitive analysis by using an interactive browser become a powerful and welcomed way. In this paper, we develop an effective sequence and chromatin interaction data display browser called HiBrowser for visualizing and analyzing Hi-C data and their associated genetic and epigenetic annotations. The advantages of HiBrowser are flexible multi-omics navigation, novel multidimensional synchronization comparisons and dynamic interaction system. In particular, HiBrowser first provides an out of the box web service and allows flexible and dynamic reconstruction of custom annotation tracks on demand during running. In order to conveniently and intuitively analyze the similarities and differences among multiple samples, such as visual comparisons of normal and tumor tissue samples, and pan genomes of multiple (consanguineous) species, HiBrowser develops a clone mode to synchronously display the genome coordinate positions or the same regions of multiple samples on the same page of visualization. HiBrowser also supports a pluralistic and precise search on correlation data of distal cis-regulatory elements and navigation to any region on Hi-C heatmap of interest according to the searching results. HiBrowser is a no-build tool, and could be easily deployed in local server. The source code is available at https://github.com/lyotvincent/HiBrowser.

The landscape of health disparities in the UK Biobank.

The UK Biobank (UKB), a large-scale biomedical database that includes demographic and electronic health record data for more than half a million ethnically diverse participants, is a potentially valuable resource for the study of health disparities. However, publicly accessible databases that catalog health disparities in the UKB do not exist. We developed the UKB Health Disparities Browser with the aims of (i) facilitating the exploration of the landscape of health disparities in the UK and (ii) directing the attention to areas of disparities research that might have the greatest public health impact. Health disparities were characterized for UKB participant groups defined by age, country of residence, ethnic group, sex and socioeconomic deprivation. We defined disease cohorts for UKB participants by mapping participant International Classification of Diseases, Tenth Revision (ICD-10) diagnosis codes to phenotype codes (phecodes). For each of the population attributes used to define population groups, disease percent prevalence values were computed for all groups from phecode case-control cohorts, and the magnitude of the disparities was calculated by both the difference and ratio of the range of disease prevalence values among groups to identify high- and low-prevalence disparities. We identified numerous diseases and health conditions with disparate prevalence values across population attributes, and we deployed an interactive web browser to visualize the results of our analysis: https://ukbatlas.health-disparities.org. The interactive browser includes overall and group-specific prevalence data for 1513 diseases based on a cohort of >500 000 participants from the UKB. Researchers can browse and sort by disease prevalence and prevalence differences to visualize health disparities for each of the five population attributes, and users can search for diseases of interest by disease names or codes. Database URL https://ukbatlas.health-disparities.org/.

A Survey on ML4VIS: Applying Machine Learning Advances to Data Visualization.

Inspired by the great success of machine learning (ML), researchers have applied ML techniques to visualizations to achieve a better design, development, and evaluation of visualizations. This branch of studies, known as ML4VIS, is gaining increasing research attention in recent years. To successfully adapt ML techniques for visualizations, a structured understanding of the integration of ML4VIS is needed. In this article, we systematically survey 88 ML4VIS studies, aiming to answer two motivating questions: "what visualization processes can be assisted by ML?" and "how ML techniques can be used to solve visualization problems? "This survey reveals seven main processes where the employment of ML techniques can benefit visualizations: Data Processing4VIS, Data-VIS Mapping, Insight Communication, Style Imitation, VIS Interaction, VIS Reading, and User Profiling. The seven processes are related to existing visualization theoretical models in an ML4VIS pipeline, aiming to illuminate the role of ML-assisted visualization in general visualizations. Meanwhile, the seven processes are mapped into main learning tasks in ML to align the capabilities of ML with the needs in visualization. Current practices and future opportunities of ML4VIS are discussed in the context of the ML4VIS pipeline and the ML-VIS mapping. While more studies are still needed in the area of ML4VIS, we hope this article can provide a stepping-stone for future exploration. A web-based interactive browser of this survey is available at https://ml4vis.github.io.

AIRRscape: An interactive tool for exploring B-cell receptor repertoires and antibody responses.

The sequencing of antibody repertoires of B-cells at increasing coverage and depth has led to the identification of vast numbers of immunoglobulin heavy and light chains. However, the size and complexity of these Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) datasets makes it difficult to perform exploratory analyses. To aid in data exploration, we have developed AIRRscape, an R Shiny-based interactive web browser application that enables B-cell receptor (BCR) and antibody feature discovery through comparisons among multiple repertoires. Using AIRR-seq data as input, AIRRscape starts by aggregating and sorting repertoires into interactive and explorable bins of germline V-gene, germline J-gene, and CDR3 length, providing a high-level view of the entire repertoire. Interesting subsets of repertoires can be quickly identified and selected, and then network topologies of CDR3 motifs can be generated for further exploration. Here we demonstrate AIRRscape using patient BCR repertoires and sequences of published monoclonal antibodies to investigate patterns of humoral immunity to three viral pathogens: SARS-CoV-2, HIV-1, and DENV (dengue virus). AIRRscape reveals convergent antibody sequences among datasets for all three pathogens, although HIV-1 antibody datasets display limited convergence and idiosyncratic responses. We have made AIRRscape available as a web-based Shiny application, along with code on GitHub to encourage its open development and use by immuno-informaticians, virologists, immunologists, vaccine developers, and other scientists that are interested in exploring and comparing multiple immune receptor repertoires.

Unified many-worlds browsing of arbitrary physics-based animations

Manually tuning physics-based animation parameters to explore a simulation outcome space or achieve desired motion outcomes can be notoriously tedious. This problem has motivated many sophisticated and specialized optimization-based methods for fine-grained (keyframe) control, each of which are typically limited to specific animation phenomena, usually complicated, and, unfortunately, not widely used. In this paper, we propose Unified Many-Worlds Browsing (UMWB), a practical method for sample-level control and exploration of physics-based animations. Our approach supports browsing of large simulation ensembles of arbitrary animation phenomena by using a unified volumetric WORLDPACK representation based on spatiotemporally compressed voxel data associated with geometric occupancy and other low-fidelity animation state. Beyond memory reduction, the WORLDPACK representation also enables unified query support for interactive browsing: it provides fast evaluation of approximate spatiotemporal queries, such as occupancy tests that find ensemble samples ("worlds") where material is either IN or NOT IN a user-specified spacetime region. WORLDPACKS also support real-time hardware-accelerated voxel rendering by exploiting the spatially hierarchical and temporal RLE raster data structure. Our UMWB implementation supports interactive browsing (and offline refinement) of ensembles containing thousands of simulation samples, and fast spatiotemporal queries and ranking. We show UMWB results using a wide variety of physics-based animation phenomena---not just JELL-O ® .

Shared Nearest Neighbors Approach and Interactive Browser for Network Analysis of a Comprehensive Non-Small-Cell Lung Cancer Data Set.

Advances in biological measurement technologies are enabling large-scale studies of patient cohorts across multiple omics platforms. Holistic analysis of these data can generate actionable insights for translational research and necessitate new approaches for data integration and mining. We present a novel approach for integrating data across platforms on the basis of the shared nearest neighbors algorithm and use it to create a network of multiplatform data from the immunogenomic profiling of non-small-cell lung cancer project. Benchmarking demonstrates that the shared nearest neighbors-based network approach outperforms a traditional gene-gene network in capturing established interactions while providing new ones on the basis of the interplay between measurements from different platforms. When used to examine patient characteristics of interest, our approach provided signatures associated with and new leads related to recurrence and TP53 oncogenotype. The network developed offers an unprecedented, holistic view into immunogenomic profiling of non-small-cell lung cancer, which can be explored through the accompanying interactive browser that we built.

Bronchial epithelium epithelial-mesenchymal plasticity forms aberrant basaloid-like cells in vitro.

Although epithelial-mesenchymal transition (EMT) is a common feature of fibrotic lung disease, its role in fibrogenesis is controversial. Recently, aberrant basaloid cells were identified in fibrotic lung tissue as a novel epithelial cell type displaying a partial EMT phenotype. The developmental origin of these cells remains unknown. To elucidate the role of EMT in the development of aberrant basaloid cells from the bronchial epithelium, we mapped EMT-induced transcriptional changes at the population and single-cell levels. Human bronchial epithelial cells grown as submerged or air-liquid interface (ALI) cultures with or without EMT induction were analyzed by bulk and single-cell RNA-Sequencing. Comparison of submerged and ALI cultures revealed differential expression of 8,247 protein coding (PC) and 1,621 long noncoding RNA (lncRNA) genes and revealed epithelial cell-type-specific lncRNAs. Similarly, EMT induction in ALI cultures resulted in robust transcriptional reprogramming of 6,020 PC and 907 lncRNA genes. Although there was no evidence for fibroblast/myofibroblast conversion following EMT induction, cells displayed a partial EMT gene signature and an aberrant basaloid-like cell phenotype. The substantial transcriptional differences between submerged and ALI cultures highlight that care must be taken when interpreting data from submerged cultures. This work supports that lung epithelial EMT does not generate fibroblasts/myofibroblasts and confirms ALI cultures provide a physiologically relevant system to study aberrant basaloid-like cells and mechanisms of EMT. We provide a catalog of PC and lncRNA genes and an interactive browser (https://bronc-epi-in-vitro.cells.ucsc.edu/) of single-cell RNA-Seq data for further exploration of potential roles in the lung epithelium in health and lung disease.

Robust and annotation-free analysis of alternative splicing across diverse cell types in mice

Although alternative splicing is a fundamental and pervasive aspect of gene expression in higher eukaryotes, it is often omitted from single-cell studies due to quantification challenges inherent to commonly used short-read sequencing technologies. Here, we undertake the analysis of alternative splicing across numerous diverse murine cell types from two large-scale single-cell datasets-the Tabula Muris and BRAIN Initiative Cell Census Network-while accounting for understudied technical artifacts and unannotated events. We find strong and general cell-type-specific alternative splicing, complementary to total gene expression but of similar discriminatory value, and identify a large volume of novel splicing events. We specifically highlight splicing variation across different cell types in primary motor cortex neurons, bone marrow B cells, and various epithelial cells, and we show that the implicated transcripts include many genes which do not display total expression differences. To elucidate the regulation of alternative splicing, we build a custom predictive model based on splicing factor activity, recovering several known interactions while generating new hypotheses, including potential regulatory roles for novel alternative splicing events in critical genes like Khdrbs3 and Rbfox1. We make our results available using public interactive browsers to spur further exploration by the community.

The Sustainability Data Science Life Cycle for automating multi-purpose LCA workflows for the analysis of large product portfolios

Life Cycle Assessment (LCA) is a powerful and sophisticated tool to gain deep understanding of the environmental hotspots and optimization potentials of products. Yet, its cost-intensive manual data engineering and analysis workflows restrain its wider application in eco-design, green procurement, supply chain management, sustainable investment or other relevant business processes. Especially for large product portfolios and increasing reporting requirements, traditional LCA workflows and tools often fail to provide the necessary scalability. The Sustainability Data Science Life Cycle (S-DSLC) is a concept for workflow automation for multi-purpose LCA of large product portfolios. The concept integrates the frameworks of LCA, the cross-industry standard process for data mining (CRISP-DM), and the Data Science Life Cycle (DSLC). Key aspects of the concept are deep business-, stakeholder and user-understanding, deployment of LCA results in interactive browser tools (i.e. LCA-dashboards and Guided Analytics) tailored to the needs of individual roles and business processes, as well as the automation of data preparation, model generation and Life Cycle Impact Assessment based on modern data analytic tools. The demonstration of the concept shows substantial scalability improvements for dealing with large product portfolios and broad application of LCA results in various business processes.

Virtual Reality Design and Realization of Interactive Garden Landscape

It is very important to study and explore the application of virtual reality technology in landscape garden design, especially in the current environment of triple network integration and Internet of Things construction, to promote and facilitate the rapid development of digital landscape garden design in China. In this paper, we study the implementation method of virtual landscape gardening system and establish a virtual environment based on the ancient city of Yangcheng. On the computer platform, we study and realize a virtual roaming system of medium complexity with more complete roaming functions. Using the Quest3D software platform, a desktop-type virtual garden simulation system was developed, focusing on the virtual reality modeling technology method and virtual system implementation. The experimental results show that the GPU-accelerated drawing method based on GLSL can significantly improve the drawing frame rate of 3D garden landscape vegetation scenes with a small amount of scene data and has a certain feasibility. Based on the OpenSceneGraph (OSG) graphics rendering engine, the visualization of various types of 3D landscape models is realized, and the spatial layout of various types of landscape with parametric control is realized through digital vector layers, which flexibly manage and organize various garden elements and reasonably organize the spatial topological relationship between various types of landscape in 3D space. By integrating cross-platform ArcGISEngine components, the basic data of garden scenes including terrain data and vector data are managed. Through scene view cropping and hierarchical detail modeling technologies, the drawing efficiency and rendering real time of the garden landscape are improved. It realizes interactive 3D scene browsing and provides a six-degree-of-freedom all-round display of the overall landscape.

Long-read-tools.org: an interactive catalogue of analysis methods for long-read sequencing data.

BackgroundThe data produced by long-read third-generation sequencers have unique characteristics compared to short-read sequencing data, often requiring tailored analysis tools for tasks ranging from quality control to downstream processing. The rapid growth in software that addresses these challenges for different genomics applications is difficult to keep track of, which makes it hard for users to choose the most appropriate tool for their analysis goal and for developers to identify areas of need and existing solutions to benchmark against.FindingsWe describe the implementation of long-read-tools.org, an open-source database that organizes the rapidly expanding collection of long-read data analysis tools and allows its exploration through interactive browsing and filtering. The current database release contains 478 tools across 32 categories. Most tools are developed in Python, and the most frequent analysis tasks include base calling, de novo assembly, error correction, quality checking/filtering, and isoform detection, while long-read single-cell data analysis and transcriptomics are areas with the fewest tools available.ConclusionContinued growth in the application of long-read sequencing in genomics research positions the long-read-tools.org database as an essential resource that allows researchers to keep abreast of both established and emerging software to help guide the selection of the most relevant tool for their analysis needs.

Kyrix-S: Authoring Scalable Scatterplot Visualizations of Big Data.

Static scatterplots often suffer from the overdraw problem on big datasets where object overlap causes undesirable visual clutter. The use of zooming in scatterplots can help alleviate this problem. With multiple zoom levels, more screen real estate is available, allowing objects to be placed in a less crowded way. We call this type of visualization scalable scatterplot visualizations, or SSV for short. Despite the potential of SSVs, existing systems and toolkits fall short in supporting the authoring of SSVs due to three limitations. First, many systems have limited scalability, assuming that data fits in the memory of one computer. Second, too much developer work, e.g., using custom code to generate mark layouts or render objects, is required. Third, many systems focus on only a small subset of the SSV design space (e.g. supporting a specific type of visual marks). To address these limitations, we have developed Kyrix-S, a system for easy authoring of SSVs at scale. Kyrix-S derives a declarative grammar that enables specification of a variety of SSVs in a few tens of lines of code, based on an existing survey of scatterplot tasks and designs. The declarative grammar is supported by a distributed layout algorithm which automatically places visual marks onto zoom levels. We store data in a multi-node database and use multi-node spatial indexes to achieve interactive browsing of large SSVs. Extensive experiments show that 1) Kyrix-S enables interactive browsing of SSVs of billions of objects, with response times under 500ms and 2) Kyrix-S achieves 4X-9X reduction in specification compared to a state-of-the-art authoring system.

MeDAS: a Metazoan Developmental Alternative Splicing database.

Alternative splicing is widespread throughout eukaryotic genomes and greatly increases transcriptomic diversity. Many alternative isoforms have functional roles in developmental processes and are precisely temporally regulated. To facilitate the study of alternative splicing in a developmental context, we created MeDAS, a Metazoan Developmental Alternative Splicing database. MeDAS is an added-value resource that re-analyses publicly archived RNA-seq libraries to provide quantitative data on alternative splicing events as they vary across the time course of development. It has broad temporal and taxonomic scope and is intended to assist the user in identifying trends in alternative splicing throughout development. To create MeDAS, we re-analysed a curated set of 2232 Illumina polyA+ RNA-seq libraries that chart detailed time courses of embryonic and post-natal development across 18 species with a taxonomic range spanning the major metazoan lineages from Caenorhabditis elegans to human. MeDAS is freely available at https://das.chenlulab.com both as raw data tables and as an interactive browser allowing searches by species, tissue, or genomic feature (gene, transcript or exon ID and sequence). Results will provide details on alternative splicing events identified for the queried feature and can be visualised at the gene-, transcript- and exon-level as time courses of expression and inclusion levels, respectively.

OposSOM-Browser: an interactive tool to explore omics data landscapes in health science

BackgroundoposSOM is a comprehensive, machine learning based open-source data analysis software combining functionalities such as diversity analyses, biomarker selection, function mining, and visualization.ResultsThese functionalities are now available as interactive web-browser application for a broader user audience interested in extracting detailed information from high-throughput omics data sets pre-processed by oposSOM. It enables interactive browsing of single-gene and gene set profiles, of molecular ‘portrait landscapes’, of associated phenotype diversity, and signalling pathway activation patterns.ConclusionThe oposSOM-Browser makes available interactive data browsing for five transcriptome data sets of cancer (melanomas, B-cell lymphomas, gliomas) and of peripheral blood (sepsis and healthy individuals) at www.izbi.uni-leipzig.de/opossom-browser.

Making health economic models Shiny: A tutorial.

Health economic evaluation models have traditionally been built in Microsoft Excel, but more sophisticated tools are increasingly being used as model complexity and computational requirements increase. Of all the programming languages, R is most popular amongst health economists because it has a plethora of user created packages and is highly flexible. However, even with an integrated development environment such as R Studio, R lacks a simple point and click user interface and therefore requires some programming ability. This might make the switch from Microsoft Excel to R seem daunting, and it might make it difficult to directly communicate results with decisions makers and other stakeholders. The R package Shiny has the potential to resolve this limitation. It allows programmers to embed health economic models developed in R into interactive web browser based user interfaces. Users can specify their own assumptions about model parameters and run different scenario analyses, which, in the case of regular a Markov model, can be computed within seconds. This paper provides a tutorial on how to wrap a health economic model built in R into a Shiny application. We use a four-state Markov model developed by the Decision Analysis in R for Technologies in Health (DARTH) group as a case-study to demonstrate main principles and basic functionality. A more extensive tutorial, all code, and data are provided in a GitHub repository.

The TTC Data Mart: An interactive browser for threshold of toxicological concern calculations

Computational technologies hold promise for informing decisions on the use of thousands of chemicals in commerce that have little or no toxicological data. Threshold of Toxicological Concern (TTC) groups compounds based on the outcome of an established analysis the chemical structure. Characterizations of hazard for representative compounds within these groups can be used in various decision contexts to evaluate risk of compounds present in trace amounts in food, drugs, and consumer products. Here, we introduce TTC calculations for a 45,000-compound chemical universe described previously in the Collaborative Estrogen Receptor Activity Prediction Project. We present these calculations in the TTC Data Mart: a web-based interface for searching and sorting compounds by TTC. The TTC Data Mart will aid in exploiting existing computational methods at the pre-assessment phase of a tiered risk-based approach to quickly, and conservatively, prioritize thousands of untested chemicals for further study.