VIAMD: a Software for Visual Interactive Analysis of Molecular Dynamics.

The typical workflow in molecular dynamics (MD) analysis requires several separate tools, often resulting in a lack of synergy and interaction between the individual analysis steps. This article presents VIAMD, an application designed to address this issue by integrating a 3D visualization of molecular trajectories with flexible analysis components. VIAMD uses an interactive scripting interface, allowing for property definition and evaluation. The application provides context-aware suggestions and expression feedback through information and visualizations. The user-defined properties can be explored and analyzed through the various components. This enables correlation with spatial conformations, statistical analysis of distributions, and powerful aggregation of multidimensional properties such as spatial distribution functions. VIAMD has the potential to advance research in many scientific disciplines and is a promising solution for improving the workflow of MD visualization and analysis.

Visualization for Diagnostic Review of Copy Number Variants in Complex DNA Sequencing Data.

Genomics is at the core of precision medicine, and there are high expectations on genomics-enabled improvement of patient outcomes in the years to come. Around the world, initiatives to increase the use of DNA sequencing in clinical routine are being deployed, such as the use of broad panels in the standard care for oncology patients. Such a development comes at the cost of increased demands on throughput in genomic data analysis. In this paper, we use the task of copy number variant (CNV) analysis as a context for exploring visualization concepts for clinical genomics. CNV calls are generated algorithmically, but time-consuming manual intervention is needed to separate relevant findings from irrelevant ones in the resulting large call candidate lists. We present a visualization environment, named Copycat, to support this review task in a clinical scenario. Key components are a scatter-glyph plot replacing the traditional list visualization, and a glyph representation designed for at-a-glance relevance assessments. Moreover, we present results from a formative evaluation of the prototype by domain specialists, from which we elicit insights to guide both prototype improvements and visualization for clinical genomics in general.

A Computational Design Pipeline to Fabricate Sensing Network Physicalizations.

Interaction is critical for data analysis and sensemaking. However, designing interactive physicalizations is challenging as it requires cross-disciplinary knowledge in visualization, fabrication, and electronics. Interactive physicalizations are typically produced in an unstructured manner, resulting in unique solutions for a specific dataset, problem, or interaction that cannot be easily extended or adapted to new scenarios or future physicalizations. To mitigate these challenges, we introduce a computational design pipeline to 3D print network physicalizations with integrated sensing capabilities. Networks are ubiquitous, yet their complex geometry also requires significant engineering considerations to provide intuitive, effective interactions for exploration. Using our pipeline, designers can readily produce network physicalizations supporting selection-the most critical atomic operation for interaction-by touch through capacitive sensing and computational inference. Our computational design pipeline introduces a new design paradigm by concurrently considering the form and interactivity of a physicalization into one cohesive fabrication workflow. We evaluate our approach using (i) computational evaluations, (ii) three usage scenarios focusing on general visualization tasks, and (iii) expert interviews. The design paradigm introduced by our pipeline can lower barriers to physicalization research, creation, and adoption.

Visual Analytics of Multivariate Networks with Representation Learning and Composite Variable Construction.

Multivariate networks are commonly found in realworld data-driven applications. Uncovering and understanding the relations of interest in multivariate networks is not a trivial task. This paper presents a visual analytics workflow for studying multivariate networks to extract associations between different structural and semantic characteristics of the networks (e.g., what are the combinations of attributes largely relating to the density of a social network?). The workflow consists of a neuralnetwork- based learning phase to classify the data based on the chosen input and output attributes, a dimensionality reduction and optimization phase to produce a simplified set of results for examination, and finally an interpreting phase conducted by the user through an interactive visualization interface. A key part of our design is a composite variable construction step that remodels nonlinear features obtained by neural networks into linear features that are intuitive to interpret. We demonstrate the capabilities of this workflow with multiple case studies on networks derived from social media usage and also evaluate the workflow with qualitative feedback from experts.

The thorny complexities of visualization research for clinical settings: A case study from genomics.

In this perspective article we discuss a certain type of research on visualization for bioinformatics data, namely, methods targeting clinical use. We argue that in this subarea additional complex challenges come into play, particularly so in genomics. We here describe four such challenge areas, elicited from a domain characterization effort in clinical genomics. We also list opportunities for visualization research to address clinical challenges in genomics that were uncovered in the case study. The findings are shown to have parallels with experiences from the diagnostic imaging domain.

A Visual Environment for Data Driven Protein Modeling and Validation.

In structural biology, validation and verification of new atomic models are crucial and necessary steps which limit the production of reliable molecular models for publications and databases. An atomic model is the result of meticulous modeling and matching and is evaluated using a variety of metrics that provide clues to improve and refine the model so it fits our understanding of molecules and physical constraints. In cryo electron microscopy (cryo-EM) the validation is also part of an iterative modeling process in which there is a need to judge the quality of the model during the creation phase. A shortcoming is that the process and results of the validation are rarely communicated using visual metaphors. This work presents a visual framework for molecular validation. The framework was developed in close collaboration with domain experts in a participatory design process. Its core is a novel visual representation based on 2D heatmaps that shows all available validation metrics in a linear fashion, presenting a global overview of the atomic model and provide domain experts with interactive analysis tools. Additional information stemming from the underlying data, such as a variety of local quality measures, is used to guide the user's attention toward regions of higher relevance. Linked with the heatmap is a three-dimensional molecular visualization providing the spatial context of the structures and chosen metrics. Additional views of statistical properties of the structure are included in the visual framework. We demonstrate the utility of the framework and its visual guidance with examples from cryo-EM.

Tracking Internal Frames of Reference for Consistent Molecular Distribution Functions.

In molecular analysis, spatial distribution functions (SDF) are fundamental instruments in answering questions related to spatial occurrences and relations of atomic structures over time. Given a molecular trajectory, SDFs can, for example, reveal the occurrence of water in relation to particular structures and hence provide clues of hydrophobic and hydrophilic regions. For the computation of meaningful distribution functions, the definition of molecular reference structures is essential. Therefore we introduce the concept of an internal frame of reference (IFR) for labeled point sets that represent selected molecular structures, and we propose an algorithm for tracking the IFR over time and space using a variant of Kabsch's algorithm. This approach lets us generate a consistent space for the aggregation of the SDF for molecular trajectories and molecular ensembles. We demonstrate the usefulness of the technique by applying it to temporal molecular trajectories as well as ensemble datasets. The examples include different docking scenarios with DNA, insulin, and aspirin.

Can Visualization Alleviate Dichotomous Thinking? Effects of Visual Representations on the Cliff Effect.

Common reporting styles for statistical results in scientific articles, such as p-values and confidence intervals (CI), have been reported to be prone to dichotomous interpretations, especially with respect to the null hypothesis significance testing framework. For example when the p-value is small enough or the CIs of the mean effects of a studied drug and a placebo are not overlapping, scientists tend to claim significant differences while often disregarding the magnitudes and absolute differences in the effect sizes. This type of reasoning has been shown to be potentially harmful to science. Techniques relying on the visual estimation of the strength of evidence have been recommended to reduce such dichotomous interpretations but their effectiveness has also been challenged. We ran two experiments on researchers with expertise in statistical analysis to compare several alternative representations of confidence intervals and used Bayesian multilevel models to estimate the effects of the representation styles on differences in researchers' subjective confidence in the results. We also asked the respondents' opinions and preferences in representation styles. Our results suggest that adding visual information to classic CI representation can decrease the tendency towards dichotomous interpretations - measured as the 'cliff effect': the sudden drop in confidence around p-value 0.05 - compared with classic CI visualization and textual representation of the CI with p-values. All data and analyses are publicly available at https://github.com/helske/statvis.

Interactive Visualization of Atmospheric Effects for Celestial Bodies.

We present an atmospheric model tailored for the interactive visualization of planetary surfaces. As the exploration of the solar system is progressing with increasingly accurate missions and instruments, the faithful visualization of planetary environments is gaining increasing interest in space research, mission planning, and science communication and education. Atmospheric effects are crucial in data analysis and to provide contextual information for planetary data. Our model correctly accounts for the non-linear path of the light inside the atmosphere (in Earth's case), the light absorption effects by molecules and dust particles, such as the ozone layer and the Martian dust, and a wavelength-dependent phase function for Mie scattering. The mode focuses on interactivity, versatility, and customization, and a comprehensive set of interactive controls make it possible to adapt its appearance dynamically. We demonstrate our results using Earth and Mars as examples. However, it can be readily adapted for the exploration of other atmospheres found on, for example, of exoplanets. For Earth's atmosphere, we visually compare our results with pictures taken from the International Space Station and against the CIE clear sky model. The Martian atmosphere is reproduced based on available scientific data, feedback from domain experts, and is compared to images taken by the Curiosity rover. The work presented here has been implemented in the OpenSpace system, which enables interactive parameter setting and real-time feedback visualization targeting presentations in a wide range of environments, from immersive dome theaters to virtual reality headsets.

[Clinical translation of genomic medicine]. / Stor potential när genomikdata kan implementeras i klinisk rutin.

Recent technical developments and early clinical examples support that precision medicine has potential to provide novel diagnostic and therapeutic solutions for patients with complex diseases, who are not responding to existing therapies. Those solutions will require integration of genomic data with routine clinical, imaging, sensor, biobank and registry data. Moreover, user-friendly tools for informed decision support for both patients and clinicians will be needed. While this will entail huge technical, ethical, societal and regulatory challenges, it may contribute to transforming and improving health care towards becoming predictive, preventive, personalised and participatory (4P-medicine).

Local ambient occlusion in direct volume rendering.

This paper presents a novel technique to efficiently compute illumination for Direct Volume Rendering using a local approximation of ambient occlusion to integrate the intensity of incident light for each voxel. An advantage with this local approach is that fully shadowed regions are avoided, a desirable feature in many applications of volume rendering such as medical visualization. Additional transfer function interactions are also presented, for instance, to highlight specific structures with luminous tissue effects and create an improved context for semitransparent tissues with a separate absorption control for the illumination settings. Multiresolution volume management and GPU-based computation are used to accelerate the calculations and support large data sets. The scheme yields interactive frame rates with an adaptive sampling approach for incrementally refined illumination under arbitrary transfer function changes. The illumination effects can give a better understanding of the shape and density of tissues and so has the potential to increase the diagnostic value of medical volume rendering. Since the proposed method is gradient-free, it is especially beneficial at the borders of clip planes, where gradients are undefined, and for noisy data sets.

Spatial conditioning of transfer functions using local material distributions.

In many applications of Direct Volume Rendering (DVR) the importance of a certain material or feature is highly dependent on its relative spatial location. For instance, in the medical diagnostic procedure, the patient's symptoms often lead to specification of features, tissues and organs of particular interest. One such example is pockets of gas which, if found inside the body at abnormal locations, are a crucial part of a diagnostic visualization. This paper presents an approach that enhances DVR transfer function design with spatial localization based on user specified material dependencies. Semantic expressions are used to define conditions based on relations between different materials, such as only render iodine uptake when close to liver. The underlying methods rely on estimations of material distributions which are acquired by weighing local neighborhoods of the data against approximations of material likelihood functions. This information is encoded and used to influence rendering according to the user's specifications. The result is improved focus on important features by allowing the user to suppress spatially less-important data. In line with requirements from actual clinical DVR practice, the methods do not require explicit material segmentation that would be impossible or prohibitively time-consuming to achieve in most real cases. The scheme scales well to higher dimensions which accounts for multi-dimensional transfer functions and multivariate data. Dual-Energy Computed Tomography, an important new modality in radiology, is used to demonstrate this scalability. In several examples we show significantly improved focus on clinically important aspects in the rendered images.

Advancing the state-of-the-art for Virtual Autopsies--initial forensic workflow study.

There are numerous advantages described of how imaging technology can support forensic examinations. However, postmortem examinations of bodies are mainly performed to address demands which differ from those of traditional clinical image processing. This needs to be kept in mind when gathering information from image data sets for forensic purposes. To support radiologists and forensic clinicians using Virtual Autopsy technologies, an initial workflow study regarding post-mortem imaging has been performed, aiming to receive an improved understanding of how Virtual Autopsy workstations, image data sets and processes can be adjusted to support and improve conventional autopsies. This paper presents potential impacts and a current forensic Virtual Autopsy workflow aiming to form a foundation for collaborative procedures that increase the value of Virtual Autopsy. The workflow study will provide an increased and mutual understanding of involved professionals. In addition, insight into future forensic workflows based on demands from both forensic and radiologist perspectives bring visualization and medical informatics researchers together to develop and improve the technology and software needed.

Inviwo - A Visualization System with Usage Abstraction Levels.

The complexity of today's visualization applications demands specific visualization systems tailored for the development of these applications. Frequently, such systems utilize levels of abstraction to improve the application development process, for instance by providing a data flow network editor. Unfortunately, these abstractions result in several issues, which need to be circumvented through an abstraction-centered system design. Often, a high level of abstraction hides low level details, which makes it difficult to directly access the underlying computing platform, which would be important to achieve an optimal performance. Therefore, we propose a layer structure developed for modern and sustainable visualization systems allowing developers to interact with all contained abstraction levels. We refer to this interaction capabilities as usage abstraction levels, since we target application developers with various levels of experience. We formulate the requirements for such a system, derive the desired architecture, and present how the concepts have been exemplary realized within the Inviwo visualization system. Furthermore, we address several specific challenges that arise during the realization of such a layered architecture, such as communication between different computing platforms, performance centered encapsulation, as well as layer-independent development by supporting cross layer documentation and debugging capabilities.

OpenSpace: A System for Astrographics.

Human knowledge about the cosmos is rapidly increasing as instruments and simulations are generating new data supporting the formation of theory and understanding of the vastness and complexity of the universe. OpenSpace is a software system that takes on the mission of providing an integrated view of all these sources of data and supports interactive exploration of the known universe from the millimeter scale showing instruments on spacecrafts to billions of light years when visualizing the early universe. The ambition is to support research in astronomy and space exploration, science communication at museums and in planetariums as well as bringing exploratory astrographics to the class room. There is a multitude of challenges that need to be met in reaching this goal such as the data variety, multiple spatio-temporal scales, collaboration capabilities, etc. Furthermore, the system has to be flexible and modular to enable rapid prototyping and inclusion of new research results or space mission data and thereby shorten the time from discovery to dissemination. To support the different use cases the system has to be hardware agnostic and support a range of platforms and interaction paradigms. In this paper we describe how OpenSpace meets these challenges in an open source effort that is paving the path for the next generation of interactive astrographics.

Haptic rendering of dynamic volumetric data.

With current methods for volume haptics in scientific visualization, features in time-varying data can freely move straight through the haptic probe without generating any haptic feedback the algorithms are simply not designed to handle variation with time but consider only the instantaneous configuration when the haptic feedback is calculated. This article introduces haptic rendering of dynamic volumetric data to provide a means for haptic exploration of dynamic behaviour in volumetric data. We show how haptic feedback can be produced that is consistent with volumetric data moving within the virtual environment and with data that, in itself, evolves over time. Haptic interaction with time-varying data is demonstrated by allowing palpation of a CT sequence of a beating human heart.

OpenSpace: Bringing NASA Missions to the Public.

This viewpoint presents OpenSpace, an open-source astrovisualization software project designed to bridge the gap between scientific discoveries and their public dissemination. A wealth of data exists for space missions from NASA and other sources. OpenSpace brings together this data and combines it in a range of immersive settings. Through non-linear storytelling and guided exploration, interactive immersive experiences help the public to engage with advanced space mission data and models, and thus be better informed and educated about NASA missions, the solar system and outer space. We demonstrate this capability by exploring the OSIRIS-Rex mission.

Exploranation: A New Science Communication Paradigm.

Science communication is facing a paradigm shift, based on the convergence of exploratory and explanatory visualization. In this article, we coin the term exploranation to denote the way in which visualization methods from scientific exploration can be used to communicate results and how methods in explanatory visualization can enrich exploration.

Interactive Visualization of 3D Histopathology in Native Resolution.

We present a visualization application that enables effective interactive visual analysis of large-scale 3D histopathology, that is, high-resolution 3D microscopy data of human tissue. Clinical work flows and research based on pathology have, until now, largely been dominated by 2D imaging. As we will show in the paper, studying volumetric histology data will open up novel and useful opportunities for both research and clinical practice. Our starting point is the current lack of appropriate visualization tools in histopathology, which has been a limiting factor in the uptake of digital pathology. Visualization of 3D histology data does pose difficult challenges in several aspects. The full-color datasets are dense and large in scale, on the order of 100,000 × 100,000× 100 voxels. This entails serious demands on both rendering performance and user experience design. Despite this, our developed application supports interactive study of 3D histology datasets at native resolution. Our application is based on tailoring and tuning of existing methods, system integration work, as well as a careful study of domain specific demands emanating from a close participatory design process with domain experts as team members. Results from a user evaluation employing the tool demonstrate a strong agreement among the 14 participating pathologists that 3D histopathology will be a valuable and enabling tool for their work.

Binding sites for luminescent amyloid biomarkers from non-biased molecular dynamics simulations.

A very stable binding site for the interaction between a pentameric oligothiophene and an amyloid-ß(1-42) fibril has been identified by means of non-biased molecular dynamics simulations. In this site, the probe is locked in an all-trans conformation with a Coulombic binding energy of 1200 kJ mol-1 due to the interactions between the anionic carboxyl groups of the probe and the cationic ε-amino groups in the lysine side chain. Upon binding, the conformationally restricted probes show a pronounced increase in molecular planarity. This is in line with the observed changes in luminescence properties that serve as the foundation for their use as biomarkers.