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This article reports on an in-depth study that investigates barriers to network exploration with visualizations. Network visualization tools are becoming increasingly popular, but little is known about how analysts plan and engage in the visual exploration of network data-which exploration strategies they employ, and how they prepare their data, define questions, and decide on visual mappings. Our study involved a series of workshops, interaction logging, and observations from a 6-week network exploration course. Our findings shed light on the stages that define analysts' approaches to network visualization and barriers experienced by some analysts during their network visualization processes. These barriers mainly appear before using a specific tool and include defining exploration goals, identifying relevant network structures and abstractions, or creating appropriate visual mappings for their network data. Our findings inform future work in visualization education and analyst-centered network visualization tool design.
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Choosing optimal outcome measures maximizes statistical power, accelerates discovery and improves reliability in early-phase trials. We devised and evaluated a modification to a pragmatic measure of oxygenation function, the [Formula: see text] ratio. Because of the ceiling effect in oxyhaemoglobin saturation, [Formula: see text] ratio ceases to reflect pulmonary oxygenation function at high [Formula: see text] values. We found that the correlation of [Formula: see text] with the reference standard ([Formula: see text]/[Formula: see text] ratio) improves substantially when excluding [Formula: see text] and refer to this measure as [Formula: see text]. Using observational data from 39,765 hospitalised COVID-19 patients, we demonstrate that [Formula: see text] is predictive of mortality, and compare the sample sizes required for trials using four different outcome measures. We show that a significant difference in outcome could be detected with the smallest sample size using [Formula: see text]. We demonstrate that [Formula: see text] is an effective intermediate outcome measure in COVID-19. It is a non-invasive measurement, representative of disease severity and provides greater statistical power.
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COVID-19 , Humanos , Reprodutibilidade dos Testes , COVID-19/diagnóstico , Pulmão , Tamanho da AmostraRESUMO
Diagrams constructed from standardized glyphs are central to communicating complex design information in many engineering fields. For example, circuit diagrams are commonplace in electronics and allow for a suitable abstraction of the physical system that helps support the design process. With the development of the Synthetic Biology Open Language Visual (SBOLv), bioengineers are now positioned to better describe and share their biological designs visually. However, the development of computational tools to support the creation of these diagrams is currently hampered by an excessive burden in maintenance due to the large and expanding number of glyphs present in the standard. Here, we present a Python package called paraSBOLv that enables access to the full suite of SBOLv glyphs through the use of machine-readable parametric glyph definitions. These greatly simplify the rendering process while allowing extensive customization of the resulting diagrams. We demonstrate how the adoption of paraSBOLv can accelerate the development of highly specialized biodesign visualization tools or even form the basis for more complex software by removing the burden of maintaining glyph-specific rendering code. Looking forward, we suggest that incorporation of machine-readable parametric glyph definitions into the SBOLv standard could further simplify the development of tools to produce standard-compliant diagrams and the integration of visual standards across fields.
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VisBOL is a web-based visualization tool used to depict genetic circuit designs. This tool depicts simple DNA circuits adequately, but it has become increasingly outdated as new versions of SBOL Visual were released. This paper introduces VisBOL2, a heavily redesigned version of VisBOL that makes a number of improvements to the original VisBOL, including proper functional interaction rendering, dynamic viewing, a more maintainable code base, and modularity that facilitates compatibility with other software tools. This modularity is demonstrated by incorporating VisBOL2 into a sequence visualization plugin for SynBioHub.
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Redes Reguladoras de Genes , Modelos Genéticos , Software , Biologia SintéticaRESUMO
People who engineer biological organisms often find it useful to draw diagrams in order to communicate both the structure of the nucleic acid sequences that they are engineering and the functional relationships between sequence features and other molecular species. Some typical practices and conventions have begun to emerge for such diagrams. SBOL Visual aims to organize and systematize such conventions in order to produce a coherent language for expressing the structure and function of genetic designs. This document details version 3.0 of SBOL Visual, a new major revision of the standard. The major difference between SBOL Visual 3 and SBOL Visual 2 is that diagrams and glyphs are defined with respect to the SBOL 3 data model rather than the SBOL 2 data model. A byproduct of this change is that the use of dashed undirected lines for subsystem mappings has been removed, pending future determination on how to represent general SBOL 3 constraints; in the interim, this annotation can still be used as an annotation. Finally, deprecated material has been removed from collection of glyphs: the deprecated "insulator" glyph and "macromolecule" alternative glyphs have been removed, as have the deprecated BioPAX alternatives to SBO terms.
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Linguagens de Programação , Biologia Sintética , Humanos , IdiomaRESUMO
People who are engineering biological organisms often find it useful to communicate in diagrams, both about the structure of the nucleic acid sequences that they are engineering and about the functional relationships between sequence features and other molecular species. Some typical practices and conventions have begun to emerge for such diagrams. The Synthetic Biology Open Language Visual (SBOL Visual) has been developed as a standard for organizing and systematizing such conventions in order to produce a coherent language for expressing the structure and function of genetic designs. This document details version 2.3 of SBOL Visual, which builds on the prior SBOL Visual 2.2 in several ways. First, the specification now includes higher-level "interactions with interactions," such as an inducer molecule stimulating a repression interaction. Second, binding with a nucleic acid backbone can be shown by overlapping glyphs, as with other molecular complexes. Finally, a new "unspecified interaction" glyph is added for visualizing interactions whose nature is unknown, the "insulator" glyph is deprecated in favor of a new "inert DNA spacer" glyph, and the polypeptide region glyph is recommended for showing 2A sequences.
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Linguagens de Programação , Biologia Sintética , Humanos , IdiomaRESUMO
BACKGROUND: Prognostic models to predict the risk of clinical deterioration in acute COVID-19 cases are urgently required to inform clinical management decisions. METHODS: We developed and validated a multivariable logistic regression model for in-hospital clinical deterioration (defined as any requirement of ventilatory support or critical care, or death) among consecutively hospitalised adults with highly suspected or confirmed COVID-19 who were prospectively recruited to the International Severe Acute Respiratory and Emerging Infections Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) study across 260 hospitals in England, Scotland, and Wales. Candidate predictors that were specified a priori were considered for inclusion in the model on the basis of previous prognostic scores and emerging literature describing routinely measured biomarkers associated with COVID-19 prognosis. We used internal-external cross-validation to evaluate discrimination, calibration, and clinical utility across eight National Health Service (NHS) regions in the development cohort. We further validated the final model in held-out data from an additional NHS region (London). FINDINGS: 74â944 participants (recruited between Feb 6 and Aug 26, 2020) were included, of whom 31â924 (43·2%) of 73â948 with available outcomes met the composite clinical deterioration outcome. In internal-external cross-validation in the development cohort of 66â705 participants, the selected model (comprising 11 predictors routinely measured at the point of hospital admission) showed consistent discrimination, calibration, and clinical utility across all eight NHS regions. In held-out data from London (n=8239), the model showed a similarly consistent performance (C-statistic 0·77 [95% CI 0·76 to 0·78]; calibration-in-the-large 0·00 [-0·05 to 0·05]); calibration slope 0·96 [0·91 to 1·01]), and greater net benefit than any other reproducible prognostic model. INTERPRETATION: The 4C Deterioration model has strong potential for clinical utility and generalisability to predict clinical deterioration and inform decision making among adults hospitalised with COVID-19. FUNDING: National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, Department for International Development, Bill & Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, NIHR HPRU in Respiratory Infections at Imperial College London.
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COVID-19/diagnóstico , Regras de Decisão Clínica , Tomada de Decisão Clínica/métodos , Deterioração Clínica , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , COVID-19/terapia , Cuidados Críticos/estatística & dados numéricos , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente/estatística & dados numéricos , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Respiração Artificial/estatística & dados numéricos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Reino Unido/epidemiologiaRESUMO
The Synthetic Biology Open Language (SBOL) is a community-developed data standard that allows knowledge about biological designs to be captured using a machine-tractable, ontology-backed representation that is built using Semantic Web technologies. While early versions of SBOL focused only on the description of DNA-based components and their sub-components, SBOL can now be used to represent knowledge across multiple scales and throughout the entire synthetic biology workflow, from the specification of a single molecule or DNA fragment through to multicellular systems containing multiple interacting genetic circuits. The third major iteration of the SBOL standard, SBOL3, is an effort to streamline and simplify the underlying data model with a focus on real-world applications, based on experience from the deployment of SBOL in a variety of scientific and industrial settings. Here, we introduce the SBOL3 specification both in comparison to previous versions of SBOL and through practical examples of its use.
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Synthetic biology builds upon genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. When designing a synthetic system, synthetic biologists need to exchange information about multiple types of molecules, the intended behavior of the system, and actual experimental measurements. The Synthetic Biology Open Language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, following an open community process involving both wet bench scientists and dry scientific modelers and software developers, across academia, industry, and other institutions. This document describes SBOL 3.0.0, which condenses and simplifies previous versions of SBOL based on experiences in deployment across a variety of scientific and industrial settings. In particular, SBOL 3.0.0, (1) separates sequence features from part/sub-part relationships, (2) renames Component Definition/Component to Component/Sub-Component, (3) merges Component and Module classes, (4) ensures consistency between data model and ontology terms, (5) extends the means to define and reference Sub-Components, (6) refines requirements on object URIs, (7) enables graph-based serialization, (8) moves Systems Biology Ontology (SBO) for Component types, (9) makes all sequence associations explicit, (10) makes interfaces explicit, (11) generalizes Sequence Constraints into a general structural Constraint class, and (12) expands the set of allowed constraints.
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Linguagens de Programação , Biologia Sintética , Idioma , Modelos Biológicos , SoftwareRESUMO
People who are engineering biological organisms often find it useful to communicate in diagrams, both about the structure of the nucleic acid sequences that they are engineering and about the functional relationships between sequence features and other molecular species. Some typical practices and conventions have begun to emerge for such diagrams. The Synthetic Biology Open Language Visual (SBOL Visual) has been developed as a standard for organizing and systematizing such conventions in order to produce a coherent language for expressing the structure and function of genetic designs. This document details version 2.2 of SBOL Visual, which builds on the prior SBOL Visual 2.1 in several ways. First, the grounding of molecular species glyphs is changed from BioPAX to SBO, aligning with the use of SBO terms for interaction glyphs. Second, new glyphs are added for proteins, introns, and polypeptide regions (e. g., protein domains), the prior recommended macromolecule glyph is deprecated in favor of its alternative, and small polygons are introduced as alternative glyphs for simple chemicals.
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Linguagens de Programação , Biologia Sintética , Humanos , IdiomaRESUMO
Biological engineers often find it useful to communicate using diagrams. These diagrams can include information both about the structure of the nucleic acid sequences they are engineering and about the functional relationships between features of these sequences and/or other molecular species. A number of conventions and practices have begun to emerge within synthetic biology for creating such diagrams, and the Synthetic Biology Open Language Visual (SBOL Visual) has been developed as a standard to organize, systematize, and extend such conventions in order to produce a coherent visual language. Here, we describe SBOL Visual version 2, which expands previous diagram standards to include new functional interactions, categories of molecular species, support for families of glyph variants, and the ability to indicate modular structure and mappings between elements of a system. SBOL Visual 2 also clarifies a number of requirements and best practices, significantly expands the collection of glyphs available to describe genetic features, and can be readily applied using a wide variety of software tools, both general and bespoke.
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Linguagens de Programação , Biologia Sintética/métodos , Modelos Teóricos , SoftwareRESUMO
People who are engineering biological organisms often find it useful to communicate in diagrams, both about the structure of the nucleic acid sequences that they are engineering and about the functional relationships between sequence features and other molecular species . Some typical practices and conventions have begun to emerge for such diagrams. The Synthetic Biology Open Language Visual (SBOL Visual) has been developed as a standard for organizing and systematizing such conventions in order to produce a coherent language for expressing the structure and function of genetic designs. This document details version 2.1 of SBOL Visual, which builds on the prior SBOL Visual 2.0 standard by expanding diagram syntax to include methods for showing modular structure and mappings between elements of a system, interactions arrows that can split or join (with the glyph at the split or join indicating either superposition or a chemical process), and adding new glyphs for indicating genomic context (e.g., integration into a plasmid or genome) and for stop codons.
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Modelos Biológicos , Linguagens de Programação , Biologia SintéticaRESUMO
Synthetic biology builds upon the techniques and successes of genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. The field still faces substantial challenges, including long development times, high rates of failure, and poor reproducibility. One method to ameliorate these problems is to improve the exchange of information about designed systems between laboratories. The synthetic biology open language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, filling a need not satisfied by other pre-existing standards. This document details version 2.3.0 of SBOL, which builds upon version 2.2.0 published in last year's JIB Standards in Systems Biology special issue. In particular, SBOL 2.3.0 includes means of succinctly representing sequence modifications, such as insertion, deletion, and replacement, an extension to support organization and attachment of experimental data derived from designs, and an extension for describing numerical parameters of design elements. The new version also includes specifying types of synthetic biology activities, unambiguous locations for sequences with multiple encodings, refinement of a number of validation rules, improved figures and examples, and clarification on a number of issues related to the use of external ontology terms.
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Modelos Biológicos , Biologia Sintética , Biologia de Sistemas , Humanos , Linguagens de ProgramaçãoRESUMO
Visualizations of biomolecular structures empower us to gain insights into biological functions, generate testable hypotheses, and communicate biological concepts. Typical visualizations (such as ball and stick) primarily depict covalent bonds. In contrast, non-covalent contacts between atoms, which govern normal physiology, pathogenesis, and drug action, are seldom visualized. We present the Protein Contacts Atlas, an interactive resource of non-covalent contacts from over 100,000 PDB crystal structures. We developed multiple representations for visualization and analysis of non-covalent contacts at different scales of organization: atoms, residues, secondary structure, subunits, and entire complexes. The Protein Contacts Atlas enables researchers from different disciplines to investigate diverse questions in the framework of non-covalent contacts, including the interpretation of allostery, disease mutations and polymorphisms, by exploring individual subunits, interfaces, and protein-ligand contacts and by mapping external information. The Protein Contacts Atlas is available at http://www.mrc-lmb.cam.ac.uk/pca/ and also through PDBe.
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Biologia Computacional , Mapeamento de Interação de Proteínas , Proteínas/química , Sítio Alostérico , Biomarcadores/química , Cristalografia por Raios X , DNA/química , Bases de Dados de Proteínas , Humanos , Ligação de Hidrogênio , Ligantes , Modelos Moleculares , Mutação , Polimorfismo Genético , Ligação Proteica , Estrutura Secundária de Proteína , Rodopsina/químicaRESUMO
We present sbml-diff, a tool that is able to read a model of a biochemical reaction network in SBML format and produce a range of diagrams showing different levels of detail. Each diagram type can be used to visualize a single model or to visually compare two or more models. The default view depicts species as ellipses, reactions as rectangles, rules as parallelograms, and events as diamonds. A cartoon view replaces the symbols used for reactions on the basis of the associated Systems Biology Ontology terms. An abstract view represents species as ellipses and draws edges between them to indicate whether a species increases or decreases the production or degradation of another species. sbml-diff is freely licensed under the three-clause BSD license and can be downloaded from https://github.com/jamesscottbrown/sbml-diff and used as a python package called from other software, as a free-standing command-line application, or online using the form at http://sysos.eng.ox.ac.uk/tebio/upload.