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

Web Services: A Process Algebra Approach

It is now well-admitted that formal methods are helpful for many issues raised in the Web service area. In this paper we present a framework for the design and verification of WSs using process algebras and their tools. We define a two-way mapping between abstract specifications written using these calculi and executable Web services written in BPEL4WS. Several choices are available: design and correct errors in BPEL4WS, using process algebra verification tools, or design and correct in process algebra and automatically obtaining the corresponding BPEL4WS code. The approaches can be combined. Process algebra are not useful only for temporal logic verification: we remark the use of simulation/bisimulation both for verification and for the hierarchical refinement design method. It is worth noting that our approach allows the use of any process algebra depending on the needs of the user at different levels (expressiveness, existence of reasoning tools, user expertise)

Towards an ontology for process monitoring and mining

Business Process Analysis (BPA) aims at monitoring, diagnosing, simulating and mining enacted processes in order to support the analysis and enhancement of process models. An effective BPA solution must provide the means for analysing existing e-businesses at three levels of abstraction: the Business Level, the Process Level and the IT Level. BPA requires semantic information that spans these layers of abstraction and which should be easily retrieved from audit trails. To cater for this, we describe the Process Mining Ontology and the Events Ontology which aim to support the analysis of enacted processes at different levels of abstraction spanning from fine grain technical details to coarse grain aspects at the Business Level

Amorphous slicing of extended finite state machines

Slicing is useful for many Software Engineering applications and has been widely studied for three decades, but there has been comparatively little work on slicing Extended Finite State Machines (EFSMs). This paper introduces a set of dependency based EFSM slicing algorithms and an accompanying tool. We demonstrate that our algorithms are suitable for dependence based slicing. We use our tool to conduct experiments on ten EFSMs, including benchmarks and industrial EFSMs. Ours is the first empirical study of dependence based program slicing for EFSMs. Compared to the only previously published dependence based algorithm, our average slice is smaller 40% of the time and larger only 10% of the time, with an average slice size of 35% for termination insensitive slicing