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.

Adaptive cultural transmission biases in children and nonhuman primates

Comparative and evolutionary developmental analyses seek to discover the similarities and differences between humans and non-human species that illuminate both the evolutionary foundations of our nature that we share with other animals, and the distinctive characteristics that make human development unique. As our closest animal relatives, with whom we last shared common ancestry, non-human primates have beenparticularly important in this endeavour. Such studies that have focused on social learning, traditions, and culture have discovered much about the ‘how’ of social learning, concerned with key underlying processes such as imitation and emulation. One of the core discoveries is that the adaptive adjustment of social learning options to different contexts is not unique to human infants, therefore multiple new strands of research have begun to focus on more subtle questions about when, from whom, and why such learning occurs. Here we review illustrative studies on both human infants and young children and on non-human primates to identify the similarities shared more broadly across the primate order, and the apparent specialisms that distinguish human development. Adaptive biases in social learning discussed include those modulated by task comprehension, experience, conformity to majorities, and the age, skill, proficiency and familiarity of potential alternative cultural models.