Eye tracking: empirical foundations for a minimal reporting guideline.

In this paper, we present a review of how the various aspects of any study using an eye tracker (such as the instrument, methodology, environment, participant, etc.) affect the quality of the recorded eye-tracking data and the obtained eye-movement and gaze measures. We take this review to represent the empirical foundation for reporting guidelines of any study involving an eye tracker. We compare this empirical foundation to five existing reporting guidelines and to a database of 207 published eye-tracking studies. We find that reporting guidelines vary substantially and do not match with actual reporting practices. We end by deriving a minimal, flexible reporting guideline based on empirical research (Section "An empirically based minimal reporting guideline").

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 visualization 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.

Isolating the impact of visual perception on dyslexics' reading ability.

A large body of data suggests that phonological deficits play an important causal role in dyslexics' reading difficulties. The functional role of visual impairments is still highly debated. Many recent studies have shown clear visual deficits in large subgroups of dyslexics. However, the relationship between these deficits and visual routines required for reading is not clear. To assess the direct contribution of visual factors to dyslexics' slower and less accurate reading, we composed a task that was similar to single word reading in its basic visual characteristics, but had none of the other (phonological, morphological, semantic, etc.) aspects of reading. Young adult dyslexics, with average or above general cognitive abilities, and controls matched for age and cognitive skills participated in the study. We measured both SOA and contrast thresholds for identifying unfamiliar letters. Letters were chosen from an alphabet graphically similar to Hebrew and English (a subset of Georgian letters), but unfamiliar to the subjects. Effects of decreasing letter size, increasing letter crowding (by adding a flanker letter on each side) and adding white noise, were measured. Dyslexics performed as well as controls under all test conditions, and had similar effect sizes. We thus conclude that, despite the data showing that dyslexics have marked difficulties with single word reading, the cause of these difficulties is not a visual processing deficit.

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.