Changing the view:towards the theory of visualisation comprehension

The core problem of the evaluation of information visualisation is that the end product of visualisation - the comprehension of the information from the data - is difficult to measure objectively. This paper outlines a description of visualisation comprehension based on two existing theories of perception: principles of perceptual organisation and the reverse hierarchy theory. The resulting account of the processes involved in visualisation comprehension enables evaluation that is not only objective, but also non-comparative, providing an absolute efficiency classification. Finally, as a sample application of this approach, an experiment studying the benefits of interactivity in 3D scatterplots is presented

A signaling visualization toolkit to support rational design of combination therapies and biomarker discovery: SiViT

Targeted cancer therapy aims to disrupt aberrant cellular signalling pathways. Biomarkers are surrogates of pathway state, but there is limited success in translating candidate biomarkers to clinical practice due to the intrinsic complexity of pathway networks. Systems biology approaches afford better understanding of complex, dynamical interactions in signalling pathways targeted by anticancer drugs. However, adoption of dynamical modelling by clinicians and biologists is impeded by model inaccessibility. Drawing on computer games technology, we present a novel visualisation toolkit, SiViT, that converts systems biology models of cancer cell signalling into interactive simulations that can be used without specialist computational expertise. SiViT allows clinicians and biologists to directly introduce for example loss of function mutations and specific inhibitors. SiViT animates the effects of these introductions on pathway dynamics, suggesting further experiments and assessing candidate biomarker effectiveness. In a systems biology model of Her2 signalling we experimentally validated predictions using SiViT, revealing the dynamics of biomarkers of drug resistance and highlighting the role of pathway crosstalk. No model is ever complete: the iteration of real data and simulation facilitates continued evolution of more accurate, useful models. SiViT will make accessible libraries of models to support preclinical research, combinatorial strategy design and biomarker discovery

SiViT

The Signalling Visualisation Toolkit (SiViT), is a cancer cell signalling network visualisation tool that provides an intuitive games-based real-time interactive interface to models of cancer cell dynamics. SiViT provides a games-technology approach to unlocking the complexities of cancer cells to anti-cancer drugs. SiViT can load a wide range of biological models in the form of SBML, but the work focuses on the Abertay Cancer cell model. SiViT allows clinicians and biologists to directly interact with the cancer cell model, introducing drugs or mutations. SiViT animates the effects of these introductions on the internal elements of the cell pathways and nodes. Showing how the cell network responds to these introductions such as increased or decreased activity, or re-rerouting to bypass the effected region of the network. Indicating the effectiveness of drugs, drug resistance and suggesting area for further experimentation.Offering bi-directional interaction and explorations. With drug inserts updating the model in real-time. Timings of drug introduction or mutations is crucial and SiViT allows for changes to occur at specific timings and model the result. This is critical in the exploration of combination therapees. SiViT follows the visual guidelines from existing literature on cell networking and dynamics, with ongoing HCI work being conducted to ensure information is visualised accessibly. SiViT was part of the UKRI Main Exhibition Stand at the American Association for the Advancement of Science 2019 conference. SiViT was the catalyst for a new 4-year project led by Macmillan Cancer Support on optimising health and social care service provision through interactive network visualisation.<br/

Engineering simulations for cancer systems biology

Computer simulation can be used to inform in vivo and in vitro experimentation, enabling rapid, low-cost hypothesis generation and directing experimental design in order to test those hypotheses. In this way, in silico models become a scientific instrument for investigation, and so should be developed to high standards, be carefully calibrated and their findings presented in such that they may be reproduced. Here, we outline a framework that supports developing simulations as scientific instruments, and we select cancer systems biology as an exemplar domain, with a particular focus on cellular signalling models. We consider the challenges of lack of data, incomplete knowledge and modelling in the context of a rapidly changing knowledge base. Our framework comprises a process to clearly separate scientific and engineering concerns in model and simulation development, and an argumentation approach to documenting models for rigorous way of recording assumptions and knowledge gaps. We propose interactive, dynamic visualisation tools to enable the biological community to interact with cellular signalling models directly for experimental design. There is a mismatch in scale between these cellular models and tissue structures that are affected by tumours, and bridging this gap requires substantial computational resource. We present concurrent programming as a technology to link scales without losing important details through model simplification. We discuss the value of combining this technology, interactive visualisation, argumentation and model separation to support development of multi-scale models that represent biologically plausible cells arranged in biologically plausible structures that model cell behaviour, interactions and response to therapeutic interventions

The Homogeneous Multiplexed System-a New Method for Autoantibody Profile in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a multi-systemic autoimmune disease leading to immunological aberrations and excessive multiple autoantibody production. The aim of this study was to investigate the prevalence of multiple autoantibodies in SLE patients utilizing the multiplex system method

The pathogenic role of circulating Hashimoto's Thyroiditis-derived TPO-positive IgG on fetal loss in naïve mice

Problem: Antibody-mediated autoimmune diseases, such as autoimmune thyroid diseases (ATD), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS), often are associated with recurrent fetal loss. One of the ATD is Hashimoto's thyroiditis which recently showed association with complications of pregnancy with increased levels of circulating autoantibodies reactive with epitopes on thyroid tissue such as thyroid peroxidase (anti-TPO). In retrospective study of sera analyses in patients with Hashimoto's thyroiditis, all patients had mainly elevated circulating anti-TPO autoantibodies. Aim: We assessed the potential of human anti-TPO highly positive IgG, derived from patients with Hashimoto's thyroiditis sera associated with complications of pregnancy, to cause directly complications of pregnancy in murine model. Method of study: Naïve ICR female mice, infused intravenously with 100&nbsp;μg of anti-TPO-positive IgG, showed increased fetal loss and embryo small for date (P&nbsp;&lt;.001) in comparison with mice passively transferred with commercial IgG or PBS. Moreover, we observed embryos small for date in the mice passively transferred with anti-TPO-positive IgG, exemplified by reduced weight of embryos and placentae (P&nbsp;=.001). Histopathological examination revealed delay in fetal development in 50% cases of anti-TPO-positive IgG-treated mice. Importantly, pathological changes in the transition zone, state of glycogen cells, and significant structural changes in the labyrinth part of placenta were observed in all anti-TPO-positive IgG samples. Conclusion: The current study shows in the first time, a direct proof of concept, on the association of human TPO-positive IgG from Hashimoto's thyroiditis patients on fetal loss induction in murine model

The Diagnostic Utility of Anti-cyclic Citrullinated Peptide Antibodies, Matrix Metalloproteinase-3, Rheumatoid Factor, Erythrocyte Sedimentation Rate, and C-reactive Protein in Patients with Erosive and Non-erosive Rheumatoid Arthritis

Objective: To compare the diagnostic utility of laboratory variables, including matrix metalloproteinase-3 (MMP-3), anti-cyclic citrullinated peptide (CCP) antibodies, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) in patients with erosive and non-erosive rheumatoid arthritis (RA)