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

Don't Repeat Yourself: Seamless Execution and Analysis of Extensive Network Experiments

This paper presents MACI, the first bespoke framework for the management, the scalable execution, and the interactive analysis of a large number of network experiments. Driven by the desire to avoid repetitive implementation of just a few scripts for the execution and analysis of experiments, MACI emerged as a generic framework for network experiments that significantly increases efficiency and ensures reproducibility. To this end, MACI incorporates and integrates established simulators and analysis tools to foster rapid but systematic network experiments. We found MACI indispensable in all phases of the research and development process of various communication systems, such as i) an extensive DASH video streaming study, ii) the systematic development and improvement of Multipath TCP schedulers, and iii) research on a distributed topology graph pattern matching algorithm. With this work, we make MACI publicly available to the research community to advance efficient and reproducible network experiments

Holistic debugging - enabling instruction set simulation for software quality assurance

We present holistic debugging, a novel method for observing execution of complex and distributed software. It builds on an instruction set simulator, which provides reproducible experiments and non-intrusive probing of state in a distributed system. Instruction set simulators, however, only provide low-level information, so a holistic debugger contains a translation framework that maps this information to higher abstraction level observation tools, such as source code debuggers. We have created Nornir, a proof-of-concept holistic debugger, built on the simulator Simics. For each observed process in the simulated system, Nornir creates an abstraction translation stack, with virtual machine translators that map machine-level storage contents (e.g. physical memory, registers) provided by Simics, to application-level data (e.g. virtual memory contents) by parsing the data structures of operating systems and virtual machines. Nornir includes a modified version of the GNU debugger (GDB), which supports non-intrusive symbolic debugging of distributed applications. Nornir's main interface is a debugger shepherd, a programmable interface that controls multiple debuggers, and allows users to coherently inspect the entire state of heterogeneous, distributed applications. It provides a robust observation platform for construction of new observation tools

An Open-Source Microscopic Traffic Simulator

We present the interactive Java-based open-source traffic simulator available at www.traffic-simulation.de. In contrast to most closed-source commercial simulators, the focus is on investigating fundamental issues of traffic dynamics rather than simulating specific road networks. This includes testing theories for the spatiotemporal evolution of traffic jams, comparing and testing different microscopic traffic models, modeling the effects of driving styles and traffic rules on the efficiency and stability of traffic flow, and investigating novel ITS technologies such as adaptive cruise control, inter-vehicle and vehicle-infrastructure communication