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

Recognizing cited facts and principles in legal judgements

In common law jurisdictions, legal professionals cite facts and legal principles from precedent cases to support their arguments before the court for their intended outcome in a current case. This practice stems from the doctrine of stare decisis, where cases that have similar facts should receive similar decisions with respect to the principles. It is essential for legal professionals to identify such facts and principles in precedent cases, though this is a highly time intensive task. In this paper, we present studies that demonstrate that human annotators can achieve reasonable agreement on which sentences in legal judgements contain cited facts and principles (respectively, κ=0.65 and κ=0.95 for inter- and intra-annotator agreement). We further demonstrate that it is feasible to automatically annotate sentences containing such legal facts and principles in a supervised machine learning framework based on linguistic features, reporting per category precision and recall figures of between 0.79 and 0.89 for classifying sentences in legal judgements as cited facts, principles or neither using a Bayesian classifier, with an overall κ of 0.72 with the human-annotated gold standard

A Labelling Framework for Probabilistic Argumentation

The combination of argumentation and probability paves the way to new accounts of qualitative and quantitative uncertainty, thereby offering new theoretical and applicative opportunities. Due to a variety of interests, probabilistic argumentation is approached in the literature with different frameworks, pertaining to structured and abstract argumentation, and with respect to diverse types of uncertainty, in particular the uncertainty on the credibility of the premises, the uncertainty about which arguments to consider, and the uncertainty on the acceptance status of arguments or statements. Towards a general framework for probabilistic argumentation, we investigate a labelling-oriented framework encompassing a basic setting for rule-based argumentation and its (semi-) abstract account, along with diverse types of uncertainty. Our framework provides a systematic treatment of various kinds of uncertainty and of their relationships and allows us to back or question assertions from the literature