Human perception of graph drawings is influenced by a variety of impact factors for which quality measures are used as a proxy indicator. The investigation of these impact factors and their effects is important for evaluating and improving quality measures and drawing algorithms, as well as improving our understanding of human graph reading. The number of edge crossings in a 2D graph drawing has long been a main quality measure for drawing evaluation. The use of stereoscopic 3D graph visualisations has gained traction over the last years, and results from several studies indicate that they can improve analysis efficiency for a range of analysis scenarios. While edge crossings can also occur in 3D, there are additional edge configurations in space that are not crossings but might be perceived as such from a specific viewpoint. Such configurations create crossings when projected on the corresponding 2D image plane and could impact readability similar to 2D crossings. In 3D drawings, the additional depth aspect and the subsequent impact factors of edge distance and relative edge direction in space might further influence the importance of those configurations for readability. As a main contribution, we for the first time discuss potential impact factors. We discuss hypotheses on their impact, and as an initial investigation explore the impact of three selected factors in an empirical study.

SUMMARY: Identifying meaningful associations between microbial communities and measured physiological or environmental variables becomes increasingly complex and computationally demanding given the continuous growth of microbiome datasets. The Coracle machine learning (ML) framework was recently developed to address this issue by integrating multiple data transformations, feature selection techniques, and ML models to yield condensed lists of features that align to target variables of interest. Further, we recently developed the UniCorP feature aggregation algorithm to identify uniquely correlated features (UNICORNs) based on the UniCor metric that iteratively enrich each taxonomic level in an automated bottom-up approach. Here we present UniCoracle, a fully automated analytical framework that integrates UniCorP's bottom-up propagation approach with a subsequent and newly developed top-down skimming (TDS) strategy, implemented with the Coracle ML framework. This combined approach leverages the inherent taxonomic structure of microbiome community data (e.g., ASVs derived from 16S rRNA gene amplicon sequencing data) to maintain predictive stability, reduce computational runtime, and identify biologically meaningful taxonomic associations. We compare the original, non-hierarchical Coracle with the TDS Coracle method and the UniCoracle approach. Evaluations across the tested datasets show that UniCoracle achieves competitive or improved predictive performance relative to both Coracle's multi-step and the TDS-based Coracle implementations and demonstrate UniCoracle's improvements in predictive accuracy over both methods. UniCoracle provides full control over feature set size and runtime, offering a streamlined and user-friendly framework for biological hypothesis generation. It identifies features (e.g., bacterial taxa) at the lowest (most specific) hierarchical level (e.g., ASV or species within a taxonomic hierarchy) that are associated with continuous target variables. AVAILABILITY: UniCoracle is freely accessible via a dedicated web server at micportal.org. The source code is open source and available on GitHub at github.com/SebastianStaab/UniCoracle.git and Zenodo at https://doi.org/10.5281/zenodo.19050205.

Problem solving is a composite cognitive process, invoking a number of cognitive mechanisms, such as perception and memory. Individuals may form collectives to solve a given problem together in collaboration, especially when complexity is perceived to be high. To determine if and when collaborative problem solving is desired in the context of visual graph analysis, we compare ad hoc pairs to individuals and nominal pairs, when solving different tasks in mixed reality. We discuss the results of an experiment with 72 participants performed in two countries and three languages. We apply the concept of task instance complexity to quantify the visual demand of tasks used in the experiment. Our results show the importance of using nominal groups as a benchmark for evaluating collaborative virtual environments. We conclude that 3D graph representation is not sufficient to induce better collaborative results compared to the benchmark.

As Immersive Analytics (IA) increasingly uses Virtual Reality (VR) for stereoscopic 3D (S3D) graph visualisation, it is crucial to understand how users perceive network structures in these immersive environments. However, little is known about how humans read S3D graphs during task solving, and how gaze behaviour indicates task performance. To address this gap, we report a user study with 18 participants asked to perform three analytical tasks on S3D graph visualisations in a VR environment. Our findings reveal systematic relationships between network structural properties and gaze behaviour. Based on these insights, we contribute a comprehensive eye tracking methodology for analysing human perception in immersive environments and establish eye tracking as a valuable tool for objectively evaluating cognitive load in S3D graph visualisation.

Edge bundling is a technique commonly used to reduce visual clutter and improve the comprehension of the drawings of large graphs. Here, we model edge bundling as a multi-objective optimization problem and employ clustering strategies, metaheuristic and Pareto analysis to identify non-dominated solutions for some classical graphs from the literature.

Human perception and understanding of graph drawings is influenced by a variety of impact factors for which quality measures such as the number of crossings are used as a proxy indicator. For the more and more common stereoscopic 3D (S3D) graph visualisations, evidence is required to better understand graph perception and its relation to quality measures. We investigate the perception of crossing configurations in S3D graph visualisations and present the results of a study.

Analysts often have to work with and make sense of large complex networks. One possible solution is to make visualisations interactive, providing users with a way to control visual clutter. Although several interactive methods have been proposed, there may be situations where some of them are too specific to be directly applicable. We have therefore identified several underlying low-level visual transformations, steered by group structures in the networks, and investigated their individual effects on user performance. This may both facilitate the development of further methods and support the generation of new hypotheses. We conducted an exploratory online experiment with 300 participants, involving five tasks, one control condition, and five group-based visual transformations: de-emphasising groups by opacity, position or size, aggregating groups, and hiding groups. The results for the three tasks that were specifically referring to groups show a high usage of the visual transformations by participants and several positive effects of the latter on accuracy, completion time, and mental effort spent. On the other hand, the two tasks that were not directly referring to groups show a lower usage of the visual transformations and the results regarding effects are rather mixed.

Graph and network visualization supports exploration, analysis and communication of relational data arising in many domains: from biological and social networks, to transportation and powergrid systems. With the arrival of AI-based question-answering tools, issues of trustworthiness and explainability of generated answers motivate a significant new role for visualization. In the context of graphs, we see the need for visualizations that can convince a critical audience that an assertion (e. g., from an AI) about the graph under analysis is valid. The requirements for such representations that convey precisely one specific graph property are quite different from standard network visualization criteria which optimize general aesthetics and readability. In this paper, we aim to provide a comprehensive introduction to visual proofs of graph properties and a foundation for further research in the area. We present a framework that defines what it means to visually prove a graph property. In the process, we introduce the notion of a visual certificate, that is, a specialized faithful graph visualization that leverages the viewer's perception, in particular, pre-attentive processing (e. g., via pop-out effects), to verify a given assertion about the represented graph. We also discuss the relationships between visual complexity, cognitive load and complexity theory, and propose a classification based on visual proof complexity. Then, we provide further examples of visual certificates for problems in different visual proof complexity classes. Finally, we conclude the paper with a discussion of the limitations of our model and some open problems.

Celtic knots, an ancient art form often linked to Celtic heritage, have been used historically in the decoration of monuments and manuscripts, often symbolizing the notions of eternity and interconnectedness. This paper introduces the framework CelticGraph designed for illustrating graphs in the style of Celtic knots and links. The process of creating these drawings raises interesting combinatorial concepts in the theory of circuits in planar graphs. Further, CelticGraph uses a novel algorithm to represent edges as Bézier curves, aiming to show each link as a smooth curve with limited curvature. We also show that with our production mechanisms we can compute any 4-regular plane graph and thereby any celtic knot or link. The CelticGraph framework for drawing graphs as celtic knots and links is implemented as an add-on of Vanted, a network visualization and analysis tool.

Graph and network visualization supports exploration, analysis and communication of relational data arising in many domains: from biological and social networks, to transportation and powergrid systems. With the arrival of AI-based question-answering tools, issues of trustworthiness and explainability of generated answers motivate a greater role for visualization. In the context of graphs, we see the need for visualizations that can convince a critical audience that an assertion about the graph under analysis is valid. The requirements for such representations that convey precisely one specific graph property are quite different from standard network visualization criteria which optimize general aesthetics and readability. In this paper, we aim to provide a comprehensive introduction to visual proofs of graph properties and a foundation for further research in the area. We present a framework that defines what it means to visually prove a graph property. In the process, we introduce the notion of a visual certificate, that is, a specialized faithful graph visualization that leverages the viewer's perception, in particular, pre-attentive processing (e. g. via pop-out effects), to verify a given assertion about the represented graph. We also discuss the relationships between visual complexity, cognitive load and complexity theory, and propose a classification based on visual proof complexity. Finally, we provide examples of visual certificates for problems in different visual proof complexity classes.

MOTIVATION: High-throughput omics methods increasingly result in large datasets including metabolomics data, which are often difficult to analyse. RESULTS: To help researchers to handle and analyse those datasets by mapping and investigating metabolomics data of multiple sampling conditions (e.g. different time points or treatments) in the context of pathways, PathwayNexus has been developed, which presents the mapping results in a matrix format, allowing users to easily observe the relations between the compounds and the pathways. It also offers functionalities like ranking, sorting, clustering, pathway views, and further analytical tools. Its primary objective is to condense large sets of pathways into smaller, more relevant subsets that align with the specific interests of the user. AVAILABILITY AND IMPLEMENTATION: The methodology presented here is implemented in PathwayNexus, an open-source add-on for Vanted available at www.cls.uni-konstanz.de/software/pathway-nexus. CONTACT: [email protected]. SUPPLEMENTARY INFORMATION: Website: www.cls.uni-konstanz.de/software/pathway-nexus.

SUMMARY: We present Coracle, an artificial intelligence (AI) framework that can identify associations between bacterial communities and continuous variables. Coracle uses an ensemble approach of prominent feature selection methods and machine learning (ML) models to identify features, i.e. bacteria, associated with a continuous variable, e.g. host thermal tolerance. The results are aggregated into a score that incorporates the performances of the different ML models and the respective feature importance, while also considering the robustness of feature selection. Additionally, regression coefficients provide first insights into the direction of the association. We show the utility of Coracle by analyzing associations between bacterial composition data (i.e. 16S rRNA Amplicon Sequence Variants, ASVs) and coral thermal tolerance (i.e. standardized short-term heat stress-derived diagnostics). This analysis identified high-scoring bacterial taxa that were previously found associated with coral thermal tolerance. Coracle scales with feature number and performs well with hundreds to thousands of features, corresponding to the typical size of current datasets. Coracle performs best if run at a higher taxonomic level first (e.g. order or family) to identify groups of interest that can subsequently be run at the ASV level. AVAILABILITY AND IMPLEMENTATION: Coracle can be accessed via a dedicated web server that allows free and simple access: http://www.micportal.org/coracle/index. The underlying code is open-source and available via GitHub https://github.com/SebastianStaab/coracle.git.

Data in behavioral research is often quantified with event-logging software, generating large data sets containing detailed information about subjects, recipients, and the duration of behaviors. Exploring and analyzing such large data sets can be challenging without tools to visualize behavioral interactions between individuals or transitions between behavioral states, yet software that can adequately visualize complex behavioral data sets is rare. TIBA (The Interactive Behavior Analyzer) is a web application for behavioral data visualization, which provides a series of interactive visualizations, including the temporal occurrences of behavioral events, the number and direction of interactions between individuals, the behavioral transitions and their respective transitional frequencies, as well as the visual and algorithmic comparison of the latter across data sets. It can therefore be applied to visualize behavior across individuals, species, or contexts. Several filtering options (selection of behaviors and individuals) together with options to set node and edge properties (in the network drawings) allow for interactive customization of the output drawings, which can also be downloaded afterwards. TIBA accepts data outputs from popular logging software and is implemented in Python and JavaScript, with all current browsers supported. The web application and usage instructions are available at tiba.inf.uni-konstanz.de. The source code is publicly available on GitHub: github.com/LSI-UniKonstanz/tiba.

Relational information between different types of entities is often modelled by a multilayer network (MLN) - a network with subnetworks represented by layers. The layers of an MLN can be arranged in different ways in a visual representation, however, the impact of the arrangement on the readability of the network is an open question. Therefore, we studied this impact for several commonly occurring tasks related to MLN analysis. Additionally, layer arrangements with a dimensionality beyond 2D, which are common in this scenario, motivate the use of stereoscopic displays. We ran a human subject study utilising a Virtual Reality headset to evaluate 2D, 2.5D, and 3D layer arrangements. The study employs six analysis tasks that cover the spectrum of an MLN task taxonomy, from path finding and pattern identification to comparisons between and across layers. We found no clear overall winner. However, we explore the task-to-arrangement space and derive empirical-based recommendations on the effective use of 2D, 2.5D, and 3D layer arrangements for MLNs.

SUMMARY: Molecular dynamics (MD) simulations of cell membranes allow for a better understanding of complex processes such as changing membrane dynamics, lipid rafts and the incorporation/passing of macromolecules into/through membranes. To explore and understand cell membrane compositions, dynamics and processes, visual analytics can help to interpret MD simulation data. APL@Voro is a software for the interactive visualization and analysis of cell membrane simulations. Here, we present the new APL@Voro, which has been continuously developed since its initial release in 2013. We discuss newly implemented algorithms, methodologies and features, such as the interactive comparison of related simulations and methods to assign lipids to either the upper or lower leaflet. AVAILABILITY AND IMPLEMENTATION: The current open-source version of APL@Voro can be downloaded from http://aplvoro.com.

Computational models are often employed in systems biology to study the dynamic behaviours of complex systems. With the rise in the number of computational models, finding ways to improve the reusability of these models and their ability to reproduce virtual experiments becomes critical. Correct and effective model annotation in community-supported and standardised formats is necessary for this improvement. Here, we present recent efforts toward a common framework for annotated, accessible, reproducible and interoperable computational models in biology, and discuss key challenges of the field.

Abstract After a long period of scepticism, more and more publications describe basic research but also practical approaches to how abstract data can be presented in immersive environments for effective and efficient data understanding. Central aspects of this important research question in immersive analytics research are concerned with the use of 3D for visualization, the embedding in the immersive space, the combination with spatial data, suitable interaction paradigms and the evaluation of use cases. We provide a characterization that facilitates the comparison and categorization of published works and present a survey of publications that gives an overview of the state of the art, current trends, and gaps and challenges in current research.

Networks are an important means for the representation and analysis of data in a variety of research and application areas. While there are many efficient methods to create layouts for networks to support their visual analysis, approaches for the comparison of networks are still underexplored. Especially when it comes to the comparison of weighted networks, which is an important task in several areas, such as biology and biomedicine, there is a lack of efficient visualization approaches. With the availability of affordable high-quality virtual reality (VR) devices, such as head-mounted displays (HMDs), the research field of immersive analytics emerged and showed great potential for using the new technology for visual data exploration. However, the use of immersive technology for the comparison of networks is still underexplored. With this work, we explore how weighted networks can be visually compared in an immersive VR environment and investigate how visual representations can benefit from the extended 3D design space. For this purpose, we develop different encodings for 3D node-link diagrams supporting the visualization of two networks within a single representation and evaluate them in a pilot user study. We incorporate the results into a more extensive user study comparing node-link representations with matrix representations encoding two networks simultaneously. The data and tasks designed for our experiments are similar to those occurring in real-world scenarios. Our evaluation shows significantly better results for the node-link representations, which is contrary to comparable 2D experiments and indicates a high potential for using VR for the visual comparison of networks.

MOTIVATION: Large metabolic models, including genome-scale metabolic models, are nowadays common in systems biology, biotechnology and pharmacology. They typically contain thousands of metabolites and reactions and therefore methods for their automatic visualization and interactive exploration can facilitate a better understanding of these models. RESULTS: We developed a novel method for the visual exploration of large metabolic models and implemented it in LMME (Large Metabolic Model Explorer), an add-on for the biological network analysis tool VANTED. The underlying idea of our method is to analyze a large model as follows. Starting from a decomposition into several subsystems, relationships between these subsystems are identified and an overview is computed and visualized. From this overview, detailed subviews may be constructed and visualized in order to explore subsystems and relationships in greater detail. Decompositions may either be predefined or computed, using built-in or self-implemented methods. Realized as add-on for VANTED, LMME is embedded in a domain-specific environment, allowing for further related analysis at any stage during the exploration. We describe the method, provide a use case and discuss the strengths and weaknesses of different decomposition methods. AVAILABILITY AND IMPLEMENTATION: The methods and algorithms presented here are implemented in LMME, an open-source add-on for VANTED. LMME can be downloaded from www.cls.uni-konstanz.de/software/lmme and VANTED can be downloaded from www.vanted.org. The source code of LMME is available from GitHub, at https://github.com/LSI-UniKonstanz/lmme.

The visualization of a network influences the quality of the mental map that the viewer develops to understand the network. In this study, we investigate the effects of a 3D immersive visualization environment compared to a traditional 2D desktop environment on the comprehension of a network’s structure. We compare the two visualization environments using three tasks—interpreting network structure, memorizing a set of nodes, and identifying the structural changes—commonly used for evaluating the quality of a mental map in network visualization. The results show that participants were able to interpret network structure more accurately when viewing the network in an immersive environment, particularly for larger networks. However, we found that 2D visualizations performed better than immersive visualization for tasks that required spatial memory.

Analysing and understanding brain function and disorder is the main focus of neuroscience. Due to the high complexity of the brain, directionality of the signal and changing activity over time, visual exploration and data analysis are difficult. For this reason, a vast amount of research challenges are still unsolved. We explored different challenges of the visual analysis of brain data and the design of corresponding immersive environments in collaboration with experts from the biomedical domain. We built a prototype of an immersive virtual reality environment to explore the design space and to investigate how brain data analysis can be supported by a variety of design choices. Our environment can be used to study the effect of different visualisations and combinations of brain data representation, as for example network layouts, anatomical mapping or time series. As a long-term goal, we aim to aid neuro-scientists in a better understanding of brain function and disorder.

The recent availability of affordable and lightweight tracking sensors allows researchers to collect large and complex movement datasets. These datasets require applications that are capable of handling them whilst providing an environment that enables the analyst(s) to focus on the task of analysing the movement in the context of the geographic environment it occurred in. We present a framework for collaborative analysis of geospatial-temporal movement data with a use-case in collective behavior analysis. It supports the concurrent usage of several program instances, allowing to have different perspectives on the same data in collocated or remote setups. The implementation can be deployed in a variety of immersive environments, e.g. on a tiled display wall or mobile VR devices.

Recent advances in tracking technology allow biologists to collect large amounts of movement data for a variety of species. Analysis of the collected data supports research on animal behaviour, influence of impact factors such as climate change and human intervention, as well as conservation programs. Analysis of the movement data is difficult, due to the nature of the research questions and the complexity of the data sets. It requires both automated analysis, e.g. for the detection of behavioural patterns, and human inspection, e.g. for interpretation, inclusion of previous knowledge, and for conclusions on future actions and decision making. We present a concept and implementation for the visual analysis of cheetah movement data in a web-based fashion that allows usage both in the field and in office environments.

Chlamydomonas reinhardtii cells have been in the focus of research for more than a decade, in particular due to its use as alternative source for energy production. However, the molecular processes in these cells are still not completely known, and 3D visualisations may help to understand these complex interactions and processes. In previous work, we presented the stereoscopic 3D (S3D) visualisation of a complete Chlamydomonas reinhardtii cell created with the 3D modelling framework Blender. This animation contained already a scene showing an illustrative membrane model of the thylakoid membrane. During discussion with domain experts, shortcomings of the visualisation for several detailed analysis questions have been identified and it was decided to redefine it.

BACKGROUND: Utilizing kinetic models of biological systems commonly require computational approaches to estimate parameters, posing a variety of challenges due to their highly non-linear and dynamic nature, which is further complicated by the issue of non-identifiability. We propose a novel parameter estimation framework by combining approaches for solving identifiability with a recently introduced filtering technique that can uniquely estimate parameters where conventional methods fail. This framework first conducts a thorough analysis to identify and classify the non-identifiable parameters and provides a guideline for solving them. If no feasible solution can be found, the framework instead initializes the filtering technique with informed prior to yield a unique solution. RESULTS: This framework has been applied to uniquely estimate parameter values for the sucrose accumulation model in sugarcane culm tissue and a gene regulatory network. In the first experiment the results show the progression of improvement in reliable and unique parameter estimation through the use of each tool to reduce and remove non-identifiability. The latter experiment illustrates the common situation where no further measurement data is available to solve the non-identifiability. These results show the successful application of the informed prior as well as the ease with which parallel data sources may be utilized without increasing the model complexity. CONCLUSION: The proposed unified framework is distinct from other approaches by providing a robust and complete solution which yields reliable and unique parameter estimation even in the face of non-identifiability.

MOTIVATION: In systems biology, kinetic models represent the biological system using a set of ordinary differential equations (ODEs). The correct values of the parameters within these ODEs are critical for a reliable study of the dynamic behaviour of such systems. Typically, it is only possible to experimentally measure a fraction of these parameter values. The rest must be indirectly determined from measurements of other quantities. In this article, we propose a novel statistical inference technique to computationally estimate these unknown parameter values. By characterizing the ODEs with non-linear state-space equations, this inference technique models the unknown parameters as hidden states, which can then be estimated from noisy measurement data. RESULTS: Here we extended the square-root unscented Kalman filter SR-UKF proposed by Merwe and Wan to include constraints with the state estimation process. We developed the constrained square-root unscented Kalman filter (CSUKF) to estimate parameters of non-linear state-space models. This probabilistic inference technique was successfully used to estimate parameters of a glycolysis model in yeast and a gene regulatory network. We showed that our method is numerically stable and can reliably estimate parameters within a biologically meaningful parameter space from noisy observations. When compared with the two common non-linear extensions of Kalman filter in addition to four widely used global optimization algorithms, CSUKF is shown to be both accurate and computationally efficient. With CSUKF, statistical analysis is straightforward, as it directly provides the uncertainty on the estimation result. AVAILABILITY AND IMPLEMENTATION: Matlab code available upon request from the author. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BACKGROUND: Biologists make frequent use of databases containing large and complex biological networks. One popular database is the Kyoto Encyclopedia of Genes and Genomes (KEGG) which uses its own graphical representation and manual layout for pathways. While some general drawing conventions exist for biological networks, arbitrary graphical representations are very common. Recently, a new standard has been established for displaying biological processes, the Systems Biology Graphical Notation (SBGN), which aims to unify the look of such maps. Ideally, online repositories such as KEGG would automatically provide networks in a variety of notations including SBGN. Unfortunately, this is non-trivial, since converting between notations may add, remove or otherwise alter map elements so that the existing layout cannot be simply reused. RESULTS: Here we describe a methodology for automatic translation of KEGG metabolic pathways into the SBGN format. We infer important properties of the KEGG layout and treat these as layout constraints that are maintained during the conversion to SBGN maps. CONCLUSIONS: This allows for the drawing and layout conventions of SBGN to be followed while creating maps that are still recognizably the original KEGG pathways. This article details the steps in this process and provides examples of the final result.

UNLABELLED: CentiLib is a library and plug-in for the comprehensive analysis and exploration of network centralities. It provides 17 different node centrality and four graph centrality measures in a user-friendly interface and supports the exploration of analysis results within the networks. Its architecture allows for easy adaption to Java-based network analysis, simulation and visualization tools, which is demonstrated by providing the plug-in for two popular network analysis tools-Cytoscape and Vanted. With the ability to quantitatively analyze biological networks in an interactive and visual manner, CentiLib supports a better understanding of complex biological networks and processes. AVAILABILITY AND IMPLEMENTATION: Software with manual and tutorials is freely available at http://centilib.ipk-gatersleben.de/.

MOTIVATION: LibSBGN is a software library for reading, writing and manipulating Systems Biology Graphical Notation (SBGN) maps stored using the recently developed SBGN-ML file format. The library (available in C++ and Java) makes it easy for developers to add SBGN support to their tools, whereas the file format facilitates the exchange of maps between compatible software applications. The library also supports validation of maps, which simplifies the task of ensuring compliance with the detailed SBGN specifications. With this effort we hope to increase the adoption of SBGN in bioinformatics tools, ultimately enabling more researchers to visualize biological knowledge in a precise and unambiguous manner. AVAILABILITY AND IMPLEMENTATION: Milestone 2 was released in December 2011. Source code, example files and binaries are freely available under the terms of either the LGPL v2.1+ or Apache v2.0 open source licenses from http://libsbgn.sourceforge.net. CONTACT: [email protected].

MOTIVATION: Modern data acquisition methods in biology allow the procurement of different types of data in increasing quantity, facilitating a comprehensive view of biological systems. As data are usually gathered and interpreted by separate domain scientists, it is hard to grasp multidomain properties and structures. Consequently, there is a need for the integration of biological data from different sources and of different types in one application, providing various visualization approaches. RESULTS: In this article, methods for the integration and visualization of multimodal biological data are presented. This is achieved based on two graphs representing the meta-relations between biological data and the measurement combinations, respectively. Both graphs are linked and serve as different views of the integrated data with navigation and exploration possibilities. Data can be combined and visualized multifariously, resulting in views of the integrated biological data. AVAILABILITY: http://vanted.ipk-gatersleben.de/hive/. CONTACT: [email protected].

BACKGROUND: In the last few years high-throughput analysis methods have become state-of-the-art in the life sciences. One of the latest developments is automated greenhouse systems for high-throughput plant phenotyping. Such systems allow the non-destructive screening of plants over a period of time by means of image acquisition techniques. During such screening different images of each plant are recorded and must be analysed by applying sophisticated image analysis algorithms. RESULTS: This paper presents an image analysis pipeline (HTPheno) for high-throughput plant phenotyping. HTPheno is implemented as a plugin for ImageJ, an open source image processing software. It provides the possibility to analyse colour images of plants which are taken in two different views (top view and side view) during a screening. Within the analysis different phenotypical parameters for each plant such as height, width and projected shoot area of the plants are calculated for the duration of the screening. HTPheno is applied to analyse two barley cultivars. CONCLUSIONS: HTPheno, an open source image analysis pipeline, supplies a flexible and adaptable ImageJ plugin which can be used for automated image analysis in high-throughput plant phenotyping and therefore to derive new biological insights, such as determination of fitness.

MOTIVATION: The recently proposed Systems Biology Graphical Notation (SBGN) provides a standard for the visual representation of biochemical and cellular processes. It aims to support more efficient and accurate communication of biological knowledge between different research communities in the life sciences. However, to increase the use of SBGN, tools for editing, validating and translating SBGN maps are desirable. RESULTS: We present SBGN-ED, a tool which allows the creation of all three types of SBGN maps from scratch or the editing of existing maps, the validation of these maps for syntactical and semantical correctness, the translation of networks from the KEGG and MetaCrop databases into SBGN and the export of SBGN maps into several file and image formats. AVAILABILITY: SBGN-ED is freely available from http://vanted.ipk-gatersleben.de/addons/sbgn-ed. The web site contains also tutorials and example files.

BACKGROUND: Solving bioinformatics tasks often requires extensive computational power. Recent trends in processor architecture combine multiple cores into a single chip to improve overall performance. The Cell Broadband Engine (CBE), a heterogeneous multi-core processor, provides power-efficient and cost-effective high-performance computing. One application area is image analysis and visualisation, in particular registration of 2D cross-sections into 3D image datasets. Such techniques can be used to put different image modalities into spatial correspondence, for example, 2D images of histological cuts into morphological 3D frameworks. RESULTS: We evaluate the CBE-driven PlayStation 3 as a high performance, cost-effective computing platform by adapting a multimodal alignment procedure to several characteristic hardware properties. The optimisations are based on partitioning, vectorisation, branch reducing and loop unrolling techniques with special attention to 32-bit multiplies and limited local storage on the computing units. We show how a typical image analysis and visualisation problem, the multimodal registration of 2D cross-sections and 3D datasets, benefits from the multi-core based implementation of the alignment algorithm. We discuss several CBE-based optimisation methods and compare our results to standard solutions. More information and the source code are available from http://cbe.ipk-gatersleben.de. CONCLUSIONS: The results demonstrate that the CBE processor in a PlayStation 3 accelerates computational intensive multimodal registration, which is of great importance in biological/medical image processing. The PlayStation 3 as a low cost CBE-based platform offers an efficient option to conventional hardware to solve computational problems in image processing and bioinformatics.

This paper investigates a new problem of visualizing a set of overlapping networks. We present two methods for constructing visualization of two and three overlapping networks in three dimensions. Our methods aim to achieve both drawing aesthetics (or conventions) for each individual network and exposing the common nodes between the overlapping networks. We evaluated our approaches using biological networks including protein interaction network, metabolic network, and gene regulatory network, from the bacterium Escherichia coli and crop plants to demonstrate their usefulness to support biological analysis.

Abstract Summary: FBA-SimVis is a VANTED plug-in for the constraint-based analysis of metabolic models with special focus on the visual exploration of metabolic flux data resulting from model analysis. The program provides a user-friendly environment for model reconstruction, constraint-based model analysis, and interactive visualization of the simulation results. With the ability to quantitatively analyse metabolic fluxes in an interactive and visual manner, FBA-SimVis supports a comprehensive understanding of constraint-based metabolic flux models in both overview and detail. Availability: Software with manual and tutorials are freely available at http://fbasimvis.ipk-gatersleben.de/ Contact: [email protected] Supplementary information: Examples and supplementary data are available at http://fbasimvis.ipk-gatersleben.de/

BACKGROUND: Complex networks are studied across many fields of science and are particularly important to understand biological processes. Motifs in networks are small connected sub-graphs that occur significantly in higher frequencies than in random networks. They have recently gathered much attention as a useful concept to uncover structural design principles of complex networks. Existing algorithms for finding network motifs are extremely costly in CPU time and memory consumption and have practically restrictions on the size of motifs. RESULTS: We present a new algorithm (Kavosh), for finding k-size network motifs with less memory and CPU time in comparison to other existing algorithms. Our algorithm is based on counting all k-size sub-graphs of a given graph (directed or undirected). We evaluated our algorithm on biological networks of E. coli and S. cereviciae, and also on non-biological networks: a social and an electronic network. CONCLUSION: The efficiency of our algorithm is demonstrated by comparing the obtained results with three well-known motif finding tools. For comparison, the CPU time, memory usage and the similarities of obtained motifs are considered. Besides, Kavosh can be employed for finding motifs of size greater than eight, while most of the other algorithms have restriction on motifs with size greater than eight. The Kavosh source code and help files are freely available at: http://Lbb.ut.ac.ir/Download/LBBsoft/Kavosh/.

BACKGROUND: Biological networks are widely used to represent processes in biological systems and to capture interactions and dependencies between biological entities. Their size and complexity is steadily increasing due to the ongoing growth of knowledge in the life sciences. To aid understanding of biological networks several algorithms for laying out and graphically representing networks and network analysis results have been developed. However, current algorithms are specialized to particular layout styles and therefore different algorithms are required for each kind of network and/or style of layout. This increases implementation effort and means that new algorithms must be developed for new layout styles. Furthermore, additional effort is necessary to compose different layout conventions in the same diagram. Also the user cannot usually customize the placement of nodes to tailor the layout to their particular need or task and there is little support for interactive network exploration. RESULTS: We present a novel algorithm to visualize different biological networks and network analysis results in meaningful ways depending on network types and analysis outcome. Our method is based on constrained graph layout and we demonstrate how it can handle the drawing conventions used in biological networks. CONCLUSION: The presented algorithm offers the ability to produce many of the fundamental popular drawing styles while allowing the exibility of constraints to further tailor these layouts.

BACKGROUND: Structural analysis of biochemical networks is a growing field in bioinformatics and systems biology. The availability of an increasing amount of biological data from molecular biological networks promises a deeper understanding but confronts researchers with the problem of combinatorial explosion. The amount of qualitative network data is growing much faster than the amount of quantitative data, such as enzyme kinetics. In many cases it is even impossible to measure quantitative data because of limitations of experimental methods, or for ethical reasons. Thus, a huge amount of qualitative data, such as interaction data, is available, but it was not sufficiently used for modeling purposes, until now. New approaches have been developed, but the complexity of data often limits the application of many of the methods. Biochemical Petri nets make it possible to explore static and dynamic qualitative system properties. One Petri net approach is model validation based on the computation of the system's invariant properties, focusing on t-invariants. T-invariants correspond to subnetworks, which describe the basic system behavior.With increasing system complexity, the basic behavior can only be expressed by a huge number of t-invariants. According to our validation criteria for biochemical Petri nets, the necessary verification of the biological meaning, by interpreting each subnetwork (t-invariant) manually, is not possible anymore. Thus, an automated, biologically meaningful classification would be helpful in analyzing t-invariants, and supporting the understanding of the basic behavior of the considered biological system. METHODS: Here, we introduce a new approach to automatically classify t-invariants to cope with network complexity. We apply clustering techniques such as UPGMA, Complete Linkage, Single Linkage, and Neighbor Joining in combination with different distance measures to get biologically meaningful clusters (t-clusters), which can be interpreted as modules. To find the optimal number of t-clusters to consider for interpretation, the cluster validity measure, Silhouette Width, is applied. RESULTS: We considered two different case studies as examples: a small signal transduction pathway (pheromone response pathway in Saccharomyces cerevisiae) and a medium-sized gene regulatory network (gene regulation of Duchenne muscular dystrophy). We automatically classified the t-invariants into functionally distinct t-clusters, which could be interpreted biologically as functional modules in the network. We found differences in the suitability of the various distance measures as well as the clustering methods. In terms of a biologically meaningful classification of t-invariants, the best results are obtained using the Tanimoto distance measure. Considering clustering methods, the obtained results suggest that UPGMA and Complete Linkage are suitable for clustering t-invariants with respect to the biological interpretability. CONCLUSION: We propose a new approach for the biological classification of Petri net t-invariants based on cluster analysis. Due to the biologically meaningful data reduction and structuring of network processes, large sets of t-invariants can be evaluated, allowing for model validation of qualitative biochemical Petri nets. This approach can also be applied to elementary mode analysis.

A standard approach to large network visualization is to provide an overview of the network and a detailed view of a small component of the graph centred around a focal node. The user explores the network by changing the focal node in the detailed view or by changing the level of detail of a node or cluster. For scalability, fast force-based layout algorithms are used for the overview and the detailed view. However, using the same layout algorithm in both views is problematic since layout for the detailed view has different requirements to that in the overview. Here we present a model in which constrained graph layout algorithms are used for layout in the detailed view. This means the detailed view has high-quality layout including sophisticated edge routing and is customisable by the user who can add placement constraints on the layout. Scalability is still ensured since the slower layout techniques are only applied to the small subgraph shown in the detailed view. The main technical innovations are techniques to ensure that the overview and detailed view remain synchronized, and modifying constrained graph layout algorithms to support smooth, stable layout. The key innovation supporting stability are new dynamic graph layout algorithms that preserve the topology or structure of the network when the user changes the focus node or the level of detail by in situ semantic zooming. We have built a prototype tool and demonstrate its use in two application domains, UML class diagrams and biological networks.

MOTIVATION: The Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway database is a very valuable information resource for researchers in the fields of life sciences. It contains metabolic and regulatory processes in the form of wiring diagrams, which can be used for browsing and information retrieval as well as a base for modeling and simulation. Thus it helps in understanding biological processes and higher-order functions of biological systems. Currently the KEGG website uses semi-static visualizations for the presentation and navigation of its pathway information. While this visualization style offers a good pathway presentation and navigation, it does not provide some of the possibilities related to dynamic visualizations, most importantly, the creation and visualization of user-specific pathways. RESULTS: This paper presents methods for the dynamic visualization, interactive navigation and editing of KEGG pathway diagrams. These diagrams, given as KEGG Markup Language (KGML) files, can be visually explored using novel approaches combining semi-static and dynamic visualization, but also edited or even newly created and then exported into KGML files. AVAILABILITY: KGML-ED, a program implementing the presented methods, is available free of charge to the scientific community at http://kgml-ed.ipk-gatersleben.de.

BACKGROUND: Recent advances with high-throughput methods in life-science research have increased the need for automatized data analysis and visual exploration techniques. Sophisticated bioinformatics tools are essential to deduct biologically meaningful interpretations from the large amount of experimental data, and help to understand biological processes. RESULTS: We present VANTED, a tool for the visualization and analysis of networks with related experimental data. Data from large-scale biochemical experiments is uploaded into the software via a Microsoft Excel-based form. Then it can be mapped on a network that is either drawn with the tool itself, downloaded from the KEGG Pathway database, or imported using standard network exchange formats. Transcript, enzyme, and metabolite data can be presented in the context of their underlying networks, e. g. metabolic pathways or classification hierarchies. Visualization and navigation methods support the visual exploration of the data-enriched networks. Statistical methods allow analysis and comparison of multiple data sets such as different developmental stages or genetically different lines. Correlation networks can be automatically generated from the data and substances can be clustered according to similar behavior over time. As examples, metabolite profiling and enzyme activity data sets have been visualized in different metabolic maps, correlation networks have been generated and similar time patterns detected. Some relationships between different metabolites were discovered which are in close accordance with the literature. CONCLUSION: VANTED greatly helps researchers in the analysis and interpretation of biochemical data, and thus is a useful tool for modern biological research. VANTED as a Java Web Start Application including a user guide and example data sets is available free of charge at http://vanted.ipk-gatersleben.de.

BACKGROUND: The elucidation of whole-cell regulatory, metabolic, interaction and other biological networks generates the need for a meaningful ranking of network elements. Centrality analysis ranks network elements according to their importance within the network structure and different centrality measures focus on different importance concepts. Central elements of biological networks have been found to be, for example, essential for viability. RESULTS: CentiBiN (Centralities in Biological Networks) is a tool for the computation and exploration of centralities in biological networks such as protein-protein interaction networks. It computes 17 different centralities for directed or undirected networks, ranging from local measures, that is, measures that only consider the direct neighbourhood of a network element, to global measures. CentiBiN supports the exploration of the centrality distribution by visualising central elements within the network and provides several layout mechanisms for the automatic generation of graphical representations of a network. It supports different input formats, especially for biological networks, and the export of the computed centralities to other tools. CONCLUSION: CentiBiN helps systems biology researchers to identify crucial elements of biological networks. CentiBiN including a user guide and example data sets is available free of charge at http://centibin.ipk-gatersleben.de/. CentiBiN is available in two different versions: a Java Web Start application and an installable Windows application.

BACKGROUND: Many attempts are being made to understand biological subjects at a systems level. A major resource for these approaches are biological databases, storing manifold information about DNA, RNA and protein sequences including their functional and structural motifs, molecular markers, mRNA expression levels, metabolite concentrations, protein-protein interactions, phenotypic traits or taxonomic relationships. The use of these databases is often hampered by the fact that they are designed for special application areas and thus lack universality. Databases on metabolic pathways, which provide an increasingly important foundation for many analyses of biochemical processes at a systems level, are no exception from the rule. Data stored in central databases such as KEGG, BRENDA or SABIO-RK is often limited to read-only access. If experimentalists want to store their own data, possibly still under investigation, there are two possibilities. They can either develop their own information system for managing that own data, which is very time-consuming and costly, or they can try to store their data in existing systems, which is often restricted. Hence, an out-of-the-box information system for managing metabolic pathway data is needed. RESULTS: We have designed META-ALL, an information system that allows the management of metabolic pathways, including reaction kinetics, detailed locations, environmental factors and taxonomic information. Data can be stored together with quality tags and in different parallel versions. META-ALL uses Oracle DBMS and Oracle Application Express. We provide the META-ALL information system for download and use. In this paper, we describe the database structure and give information about the tools for submitting and accessing the data. As a first application of META-ALL, we show how the information contained in a detailed kinetic model can be stored and accessed. CONCLUSION: META-ALL is a system for managing information about metabolic pathways. It facilitates the handling of pathway-related data and is designed to help biochemists and molecular biologists in their daily research. It is available on the Web at http://bic-gh.de/meta-all and can be downloaded free of charge and installed locally.

UNLABELLED: MAVisto is a tool for the exploration of motifs in biological networks. It provides a flexible motif search algorithm and different views for the analysis and visualization of network motifs. These views help to explore interesting motifs: the frequency of motif occurrences can be compared with randomized networks, a list of motifs along with information about structure and number of occurrences depending on the reuse of network elements shows potentially interesting motifs, a motif fingerprint reveals the overall distribution of motifs of a given size and the distribution of a particular motif in the network can be visualized using an advanced layout algorithm. AVAILABILITY: MAVisto is platform independent and available free of charge as a Java webstart application at http://mavisto.ipk-gatersleben.de/ CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Can be found at http://mavisto.ipk-gatersleben.de/