Visualization for epidemiological modelling: challenges, solutions, reflections and recommendations.

We report on an ongoing collaboration between epidemiological modellers and visualization researchers by documenting and reflecting upon knowledge constructs-a series of ideas, approaches and methods taken from existing visualization research and practice-deployed and developed to support modelling of the COVID-19 pandemic. Structured independent commentary on these efforts is synthesized through iterative reflection to develop: evidence of the effectiveness and value of visualization in this context; open problems upon which the research communities may focus; guidance for future activity of this type and recommendations to safeguard the achievements and promote, advance, secure and prepare for future collaborations of this kind. In describing and comparing a series of related projects that were undertaken in unprecedented conditions, our hope is that this unique report, and its rich interactive supplementary materials, will guide the scientific community in embracing visualization in its observation, analysis and modelling of data as well as in disseminating findings. Equally we hope to encourage the visualization community to engage with impactful science in addressing its emerging data challenges. If we are successful, this showcase of activity may stimulate mutually beneficial engagement between communities with complementary expertise to address problems of significance in epidemiology and beyond. See https://ramp-vis.github.io/RAMPVIS-PhilTransA-Supplement/. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.

Heterogeneous fractionation profiles of meta-analytic coactivation networks.

Computational cognitive neuroimaging approaches can be leveraged to characterize the hierarchical organization of distributed, functionally specialized networks in the human brain. To this end, we performed large-scale mining across the BrainMap database of coordinate-based activation locations from over 10,000 task-based experiments. Meta-analytic coactivation networks were identified by jointly applying independent component analysis (ICA) and meta-analytic connectivity modeling (MACM) across a wide range of model orders (i.e., d=20-300). We then iteratively computed pairwise correlation coefficients for consecutive model orders to compare spatial network topologies, ultimately yielding fractionation profiles delineating how "parent" functional brain systems decompose into constituent "child" sub-networks. Fractionation profiles differed dramatically across canonical networks: some exhibited complex and extensive fractionation into a large number of sub-networks across the full range of model orders, whereas others exhibited little to no decomposition as model order increased. Hierarchical clustering was applied to evaluate this heterogeneity, yielding three distinct groups of network fractionation profiles: high, moderate, and low fractionation. BrainMap-based functional decoding of resultant coactivation networks revealed a multi-domain association regardless of fractionation complexity. Rather than emphasize a cognitive-motor-perceptual gradient, these outcomes suggest the importance of inter-lobar connectivity in functional brain organization. We conclude that high fractionation networks are complex and comprised of many constituent sub-networks reflecting long-range, inter-lobar connectivity, particularly in fronto-parietal regions. In contrast, low fractionation networks may reflect persistent and stable networks that are more internally coherent and exhibit reduced inter-lobar communication.

A new approach for quantitative phosphoproteomic dissection of signaling pathways applied to T cell receptor activation.

Reversible protein phosphorylation plays a pivotal role in the regulation of cellular signaling pathways. Current approaches in phosphoproteomics focus on analysis of the global phosphoproteome in a single cellular state or of receptor stimulation time course experiments, often with a restricted number of time points. Although these studies have provided some insights into newly discovered phosphorylation sites that may be involved in pathways, they alone do not provide enough information to make precise predictions of the placement of individual phosphorylation events within a signaling pathway. Protein disruption and site-directed mutagenesis are essential to clearly define the precise biological roles of the hundreds of newly discovered phosphorylation sites uncovered in modern proteomics experiments. We have combined genetic analysis with quantitative proteomic methods and recently developed visual analysis tools to dissect the tyrosine phosphoproteome of isogenic Zap-70 tyrosine kinase null and reconstituted Jurkat T cells. In our approach, label-free quantitation using normalization to copurified phosphopeptide standards is applied to assemble high density temporal data within a single cell type, either Zap-70 null or reconstituted cells, providing a list of candidate phosphorylation sites that change in abundance after T cell stimulation. Stable isotopic labeling of amino acids in cell culture (SILAC) ratios are then used to compare Zap-70 null and reconstituted cells across a time course of receptor stimulation, providing direct information about the placement of newly observed phosphorylation sites relative to Zap-70. These methods are adaptable to any cell culture signaling system in which isogenic wild type and mutant cells have been or can be derived using any available phosphopeptide enrichment strategy.

Visual integration of quantitative proteomic data, pathways, and protein interactions.

We introduce several novel visualization and interaction paradigms for visual analysis of published protein-protein interaction networks, canonical signaling pathway models, and quantitative proteomic data. We evaluate them anecdotally with domain scientists to demonstrate their ability to accelerate the proteomic analysis process. Our results suggest that structuring protein interaction networks around canonical signaling pathway models, exploring pathways globally and locally at the same time, and driving the analysis primarily by the experimental data, all accelerate the understanding of protein pathways. Concrete proteomic discoveries within T-cells, mast cells, and the insulin signaling pathway validate the findings. The aim of the paper is to introduce novel protein network visualization paradigms and anecdotally assess the opportunity of incorporating them into established proteomic applications. We also make available a prototype implementation of our methods, to be used and evaluated by the proteomic community.

Exploring 3D DTI fiber tracts with linked 2D representations.

We present a visual exploration paradigm that facilitates navigation through complex fiber tracts by combining traditional 3D model viewing with lower dimensional representations. To this end, we create standard streamtube models along with two two-dimensional representations, an embedding in the plane and a hierarchical clustering tree, for a given set of fiber tracts. We then link these three representations using both interaction and color obtained by embedding fiber tracts into a perceptually uniform color space. We describe an anecdotal evaluation with neuroscientists to assess the usefulness of our method in exploring anatomical and functional structures in the brain. Expert feedback indicates that, while a standalone clinical use of the proposed method would require anatomical landmarks in the lower dimensional representations, the approach would be particularly useful in accelerating tract bundle selection. Results also suggest that combining traditional 3D model viewing with lower dimensional representations can ease navigation through the complex fiber tract models, improving exploration of the connectivity in the brain.

Node-Link or Adjacency Matrices: Old Question, New Insights.

Visualizing network data is applicable in domains such as biology, engineering, and social sciences. We report the results of a study comparing the effectiveness of the two primary techniques for showing network data: node-link diagrams and adjacency matrices. Specifically, an evaluation with a large number of online participants revealed statistically significant differences between the two visualizations. Our work adds to existing research in several ways. First, we explore a broad spectrum of network tasks, many of which had not been previously evaluated. Second, our study uses two large datasets, typical of many real-life networks not explored by previous studies. Third, we leverage crowdsourcing to evaluate many tasks with many participants. This paper is an expanded journal version of a Graph Drawing (GD'17) conference paper. We evaluated a second dataset, added a qualitative feedback section, and expanded the procedure, results, discussion, and limitations sections.

A Data Model and Task Space for Data of Interest (DOI) Eye-Tracking Analyses.

Eye-tracking data is traditionally analyzed by looking at where on a visual stimulus subjects fixate, or, to facilitate more advanced analyses, by using area-of-interests (AOI) defined onto visual stimuli. Recently, there is increasing interest in methods that capture what users are looking at rather than where they are looking. By instrumenting visualization code that transforms a data model into visual content, gaze coordinates reported by an eye-tracker can be mapped directly to granular data shown on the screen, producing temporal sequences of data objects that subjects viewed in an experiment. Such data collection, which is called gaze to object mapping (GTOM) or data-of-interest analysis (DOI), can be done reliably with limited overhead and can facilitate research workflows not previously possible. Our paper contributes to establishing a foundation of DOI analyses by defining a DOI data model and highlighting its differences to AOI data in structure and scale; by defining and exemplifying a space of DOI enabled tasks; by describing three concrete examples of DOI experimentation in three different domains; and by discussing immediate research challenges in creating a framework of visual support for DOI experimentation and analysis.

Analyzing Eye-Tracking Information in Visualization and Data Space: From Where on the Screen to What on the Screen.

Eye-tracking data is currently analyzed in the image space that gaze-coordinates were recorded in, generally with the help of overlays such as heatmaps or scanpaths, or with the help of manually defined areas of interest (AOI). Such analyses, which focus predominantly on where on the screen users are looking, require significant manual input and are not feasible for studies involving many subjects, long sessions, and heavily interactive visual stimuli. Alternatively, we show that it is feasible to collect and analyze eye-tracking information in data space. Specifically, the visual layout of visualizations with open source code that can be instrumented is known at rendering time, and thus can be used to relate gaze-coordinates to visualization and data objects that users view, in real time. We demonstrate the effectiveness of this approach by showing that data collected using this methodology from nine users working with an interactive visualization, was well aligned with the tasks that those users were asked to solve, and similar to annotation data produced by five human coders. Moreover, we introduce an algorithm that, given our instrumented visualization, could translate gaze-coordinates into viewed objects with greater accuracy than simply binning gazes into dynamically defined AOIs. Finally, we discuss the challenges, opportunities, and benefits of analyzing eye-tracking in visualization and data space.

Fauxvea: Crowdsourcing Gaze Location Estimates for Visualization Analysis Tasks.

We present the design and evaluation of a method for estimating gaze locations during the analysis of static visualizations using crowdsourcing. Understanding gaze patterns is helpful for evaluating visualizations and user behaviors, but traditional eye-tracking studies require specialized hardware and local users. To avoid these constraints, we developed a method called Fauxvea, which crowdsources visualization tasks on the Web and estimates gaze fixations through cursor interactions without eye-tracking hardware. We ran experiments to evaluate how gaze estimates from our method compare with eye-tracking data. First, we evaluated crowdsourced estimates for three common types of information visualizations and basic visualization tasks using Amazon Mechanical Turk (MTurk). In another, we reproduced findings from a previous eye-tracking study on tree layouts using our method on MTurk. Results from these experiments show that fixation estimates using Fauxvea are qualitatively and quantitatively similar to eye tracking on the same stimulus-task pairs. These findings suggest that crowdsourcing visual analysis tasks with static information visualizations could be a viable alternative to traditional eye-tracking studies for visualization research and design.

How to Display Group Information on Node-Link Diagrams: An Evaluation.

We present the results of evaluating four techniques for displaying group or cluster information overlaid on node-link diagrams: node coloring, GMap, BubbleSets, and LineSets. The contributions of the paper are three fold. First, we present quantitative results and statistical analyses of data from an online study in which approximately 800 subjects performed 10 types of group and network tasks in the four evaluated visualizations. Specifically, we show that BubbleSets is the best alternative for tasks involving group membership assessment; that visually encoding group information over basic node-link diagrams incurs an accuracy penalty of about 25 percent in solving network tasks; and that GMap's use of prominent group labels improves memorability. We also show that GMap's visual metaphor can be slightly altered to outperform BubbleSets in group membership assessment. Second, we discuss visual characteristics that can explain the observed quantitative differences in the four visualizations and suggest design recommendations. This discussion is supported by a small scale eye-tracking study and previous results from the visualization literature. Third, we present an easily extensible user study methodology.

What Google Maps can do for biomedical data dissemination: examples and a design study.

BACKGROUND: Biologists often need to assess whether unfamiliar datasets warrant the time investment required for more detailed exploration. Basing such assessments on brief descriptions provided by data publishers is unwieldy for large datasets that contain insights dependent on specific scientific questions. Alternatively, using complex software systems for a preliminary analysis may be deemed as too time consuming in itself, especially for unfamiliar data types and formats. This may lead to wasted analysis time and discarding of potentially useful data. RESULTS: We present an exploration of design opportunities that the Google Maps interface offers to biomedical data visualization. In particular, we focus on synergies between visualization techniques and Google Maps that facilitate the development of biological visualizations which have both low-overhead and sufficient expressivity to support the exploration of data at multiple scales. The methods we explore rely on displaying pre-rendered visualizations of biological data in browsers, with sparse yet powerful interactions, by using the Google Maps API. We structure our discussion around five visualizations: a gene co-regulation visualization, a heatmap viewer, a genome browser, a protein interaction network, and a planar visualization of white matter in the brain. Feedback from collaborative work with domain experts suggests that our Google Maps visualizations offer multiple, scale-dependent perspectives and can be particularly helpful for unfamiliar datasets due to their accessibility. We also find that users, particularly those less experienced with computer use, are attracted by the familiarity of the Google Maps API. Our five implementations introduce design elements that can benefit visualization developers. CONCLUSIONS: We describe a low-overhead approach that lets biologists access readily analyzed views of unfamiliar scientific datasets. We rely on pre-computed visualizations prepared by data experts, accompanied by sparse and intuitive interactions, and distributed via the familiar Google Maps framework. Our contributions are an evaluation demonstrating the validity and opportunities of this approach, a set of design guidelines benefiting those wanting to create such visualizations, and five concrete example visualizations.

Exploring brain connectivity with two-dimensional neural maps.

We introduce two-dimensional neural maps for exploring connectivity in the brain. For this, we create standard streamtube models from diffusion-weighted brain imaging data sets along with neural paths hierarchically projected into the plane. These planar neural maps combine desirable properties of low-dimensional representations, such as visual clarity and ease of tract-of-interest selection, with the anatomical familiarity of 3D brain models and planar sectional views. We distribute this type of visualization both in a traditional stand-alone interactive application and as a novel, lightweight web-accessible system. The web interface integrates precomputed neural-path representations into a geographical digital-maps framework with associated labels, metrics, statistics, and linkouts. Anecdotal and quantitative comparisons of the present method with a recently proposed 2D point representation suggest that our representation is more intuitive and easier to use and learn. Similarly, users are faster and more accurate in selecting bundles using the 2D path representation than the 2D point representation. Finally, expert feedback on the web interface suggests that it can be useful for collaboration as well as quick exploration of data.