Novel developments in SBGN-ED and applications

Systems Biology Graphical Notation (SBGN, http://sbgn.org) [1] is an emerging standard for graphical representations of biochemical and cellular processes studied in systems biology. Three different views (Process Description, Entity Relationship, and Activity Flow) cover several aspects of the represented processes in different levels of detail. SBGN helps to communicate biological knowledge more efficient and accurate between different research communities in the life sciences. However, to support SBGN, methods and tools for editing, validating, and translating of SBGN maps are necessary.
We present methods for these tasks and novel developments in SBGN-ED (www.sbgn-ed.org) [2], a tool which allows to create all three types of SBGN maps from scratch, to validate these maps for syntactical and semantical correctness, to translate maps from the KEGG database into SBGN, and to export SBGN maps into several file and image formats. SBGN-ED is based on VANTED (Visualization and Analysis of NeTworks containing Experimental Data, http://www.vanted.org) [3].
As applications of SBGN and SBGN-ED we present furthermore MetaCrop (http://metacrop.ipk-gatersleben.de) [4], a database that summarizes diverse information about metabolic pathways in crop plants, and RIMAS (Regulatory Interaction Maps of Arabidopsis Seed Development, http://rimas.ipk-gatersleben.de) [5], an information portal that provides a comprehensive overview of regulatory pathways and genetic interactions during Arabidopsis embryo and seed development. 

[1] Le Novère, N. et al. (2009) The Systems Biology Graphical Notation. Nature Biotechnology, 27, 735-741.
[2] Czauderna, T., Klukas, C., Schreiber, F. (2010) Editing, validating, and translating of SBGN maps. Bioinformatics, 26 (18), 2340-2341.
[3] Junker, B.H., Klukas, C., Schreiber, F. (2006) VANTED: A system for advanced data analysis and visualization in the context of biological networks. BMC Bioinformatics, 7, 109+.
[4] Grafahrend-Belau, E., Weise, S., Koschützki, D., Scholz, U., Junker, B.H., Schreiber, F. (2008) MetaCrop - A detailed database of crop plant metabolism. Nucleic Acids Research, 36, D954-D958.
[5] Junker, A., Hartmann, A., Schreiber, F., Bäumlein, H. (2010) An engineer's view on regulation of seed development. Trends in Plant Science, 15(6), 303-307.
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HTPheno: An image analysis pipeline for high-throughput plant phenotyping

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p

OntoPlot: A Novel Visualisation for Non-hierarchical Associations in Large Ontologies

Ontologies are formal representations of concepts and complex relationships among them. They have been widely used to capture comprehensive domain knowledge in areas such as biology and medicine, where large and complex ontologies can contain hundreds of thousands of concepts. Especially due to the large size of ontologies, visualisation is useful for authoring, exploring and understanding their underlying data. Existing ontology visualisation tools generally focus on the hierarchical structure, giving much less emphasis to non-hierarchical associations. In this paper we present OntoPlot, a novel visualisation specifically designed to facilitate the exploration of all concept associations whilst still showing an ontology's large hierarchical structure. This hybrid visualisation combines icicle plots, visual compression techniques and interactivity, improving space-efficiency and reducing visual structural complexity. We conducted a user study with domain experts to evaluate the usability of OntoPlot, comparing it with the de facto ontology editor Prot{\'e}g{\'e}. The results confirm that OntoPlot attains our design goals for association-related tasks and is strongly favoured by domain experts.Comment: Accepted at IEEE InfoVis 201

Human-Centred Feasibility Restoration

Decision systems for solving real-world combinatorial problems must be able to report infeasibility in such a way that users can understand the reasons behind it, and understand how to modify the problem to restore feasibility. Current methods mainly focus on reporting one or more subsets of the problem constraints that cause infeasibility. Methods that also show users how to restore feasibility tend to be less flexible and/or problem-dependent. We describe a problem-independent approach to feasibility restoration that combines existing techniques from the literature in novel ways to yield meaningful, useful, practical and flexible user support. We evaluate the resulting framework on two real-world applications

Stereoscopic space map – semi-immersive configuration of 3Dstereoscopic tours in multi-display environments

Although large-scale stereoscopic 3D environments like CAVEs are a favorable location for group presentations, the perspective projection and stereoscopic optimization usually follows a navigator-centric approach. Therefore, these presentations are usually accompanied by strong side-effects, such as motion sickness which is often caused by a disturbed stereoscopic vision. The reason is that the stereoscopic visualization is usually optimized for the only head-tracked person in the CAVE – the navigator – ignoring the needs of the real target group – the audience. To overcome this misconception, this work proposes an alternative to the head tracking-based stereoscopic effect optimization. By using an interactive virtual overview map in 3D, the pre-tour and on-tour configuration of the stereoscopic effect is provided, partly utilizing our previously published interactive projection plane approach. This Stereoscopic Space Map is visualized by the zSpace 200®, whereas the virtual world is shown on a panoramic 330° CAVE2TM. A pilot expert study with eight participants was conducted using pre-configured tours through 3D models. The comparison of the manual and automatic stereoscopic adjustment showed that the proposed approach is an appropriate alternative to the nowadays commonly used head tracking-based stereoscopic adjustment

Specifications of standards in systems and synthetic biology: Status and developments in 2020

This special issue of the Journal of Integrative Bioinformatics presents papers related to the 10th COMBINE meeting together with the annual update of COMBINE standards in systems and synthetic biology

3D-Stereoscopic Immersive Analytics Projects at Monash University and University of Konstanz

Immersive Analytics investigates how novel interaction and display technologies may support analytical reasoning and decision making. The Immersive Analytics initiative of Monash University started early 2014. Over the last few years, a number of projects have been developed or extended in this context to meet the requirements of semi- or full-immersive stereoscopic environments. Different technologies are used for this purpose: CAVE2™ (a 330 degree large-scale visualization environment which can be used for educative and scientific group presentations, analyses and discussions), stereoscopic Powerwalls (miniCAVEs, representing a segment of the CAVE2 and used for development and communication), Fishtanks, and/or HMDs (such as Oculus, VIVE, and mobile HMD approaches). Apart from CAVE2™ all systems are or will be employed on both the Monash University and the University of Konstanz side, especially to investigate collaborative Immersive Analytics. In addition, sensiLab extends most of the previous approaches by involving all senses, 3D visualization is combined with multi-sensory feedback, 3D printing, robotics in a scientific-artistic-creative environment

Distinct Genetic Risk Profile of the Rapidly Progressing Diffuse-Trickling Subtype of Geographic Atrophy in Age-Related Macular Degeneration (AMD)

PURPOSE. To genetically characterize a subphenotype of geographic atrophy (GA) in AMD associated with rapid progression and a diffuse-trickling appearance on fundus autofluorescence imaging. METHODS. Patients from the Fundus Autofluorescence in Age-Related Macular Degeneration Study were phenotyped for diffuse-trickling GA (dt-GA; n = 44). DNA was analyzed for 10 known AMD-associated genetic variants. A genetic risk score (GRS) was calculated and compared with patients with nondiffuse-trickling GA (ndt-GA; n = 311) and individuals from the 1000 genomes project (1000G; n = 267). Given the phenotypic overlap between diffuse trickling and late-onset retinal degeneration (LORD), all C1QTNF5 exons and their exon/ intron boundaries were sequenced. RESULTS. A statistically significant difference in allele frequencies between dt-GA and ndt-GA were found for CFH: rs1061170 and CFH: rs800292 (P-corrected = 0.03). The ARMS2 variant rs10490924 was significantly more frequent in dt-GA than in 1000G individuals (P-corrected < 0.01). The GRS of dt-GA patients was in-between the score of the 1000G individuals and that of patients with ndt-GA, significantly differing from both (P-corrected < 0.01). Sequencing of C1QTNF5 revealed 28 unique variants although none showed a statistically significant association with dt-GA when compared with 1000G individuals. CONCLUSIONS. The dt-GA phenotype shows a remarkably different genetic risk profile from other GA phenotypes secondary to AMD. Disease-associated C1QTNF5 mutations were not identified. Together, these results suggest that the dt-GA phenotype is associated with a genetic background substantially different from other GA phenotypes and underlines the necessity to refine the clinical phenotyping, specifically when aiming for individualized therapies in AMD

Cabozantinib in Advanced Hepatocellular Carcinoma: Efficacy and Safety Data from an International Multicenter Real-Life Cohort

Background and Aims: The multikinase inhibitor cabozantinib has been approved for hepatocellular carcinoma (HCC) previously treated with sorafenib. We report safety and efficacy data of an international, multicenter, real-life cohort of patients with advanced HCC treated with cabozantinib. Methods: Patients with HCC who were treated with cabozantinib were retrospectively identified across 11 centers in Austria, Switzerland, and Germany. Patients’ characteristics, adverse events, duration of treatment and overall survival (OS) data were analyzed until April 1, 2020. Results: Eighty-eight patients from 11 centers were included. The predominant underlying liver diseases were NAFLD/NASH in 26 (30%) and hepatitis C infection in 21 (24%) patients. Seventy-eight patients (89%) were classified as Barcelona clinic liver cancer (BCLC) stage C. Sixty patients (68%) were Child-Pugh A, whereas 22 (25%) were Child-Pugh B, respectively. Cabozantinib was used as systemic second- and third-line or later treatment in 41 (47%) and 46 (52%) patients, respectively. The following best responses under cabozantinib were documented: partial response in 6 (7%), stable disease in 28 (32%), and progressive disease in 28 (32%) patients, respectively. Fifty-two patients (59%) died during follow-up. The median OS from start of cabozantinib treatment was 7.0 months in the entire cohort and 9.7 months in Child-Pugh A patients, while Child-Pugh B patients had a median OS of 3.4 months, respectively. Thirty-seven (42%) patients fulfilled the CELESTIAL inclusion and exclusion criteria, showing a median OS of 11.1 months. Most common adverse events were fatigue (15.6%) and diarrhea (15.6%). Conclusion: Cabozantinib treatment was effective, safe, and feasible in patients with advanced HCC in patients with compensated cirrhosis. Patients in the real-life setting had more advanced liver disease – in which 25% of patients were Child-Pugh B. However, OS in patients with Child-Pugh A cirrhosis was similar to that reported in the phase 3 trial (CELESTIAL)

Toward community standards and software for whole-cell modeling

Whole-cell (WC) modeling is a promising tool for biological research, bioengineering, and medicine. However, substantial work remains to create accurate, comprehensive models of complex cells. Methods: We organized the 2015 Whole-Cell Modeling Summer School to teach WC modeling and evaluate the need for new WC modeling standards and software by recoding a recently published WC model in SBML. Results: Our analysis revealed several challenges to representing WC models using the current standards. Conclusion: We, therefore, propose several new WC modeling standards, software, and databases. Significance:We anticipate that these new standards and software will enable more comprehensive models