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.

Big data: appearance and disappearance

The mainstay of Big Data is prediction in that it allows practitioners, researchers, and policy analysts to predict trends based upon the analysis of large and varied sources of data. These can range from changing social and political opinions, patterns in crimes, and consumer behaviour. Big Data has therefore shifted the criterion of success in science from causal explanations to predictive modelling and simulation. The 19th-century science sought to capture phenomena and seek to show the appearance of it through causal mechanisms while 20th-century science attempted to save the appearance and relinquish causal explanations. Now 21st-century science in the form of Big Data is concerned with the prediction of appearances and nothing more. However, this pulls social science back in the direction of a more rule- or law-governed reality model of science and away from a consideration of the internal nature of rules in relation to various practices. In effect Big Data offers us no more than a world of surface appearance and in doing so it makes disappear any context-specific conceptual sensitivity.