Mathematical and Statistical Techniques for Systems Medicine: The Wnt Signaling Pathway as a Case Study

The last decade has seen an explosion in models that describe phenomena in systems medicine. Such models are especially useful for studying signaling pathways, such as the Wnt pathway. In this chapter we use the Wnt pathway to showcase current mathematical and statistical techniques that enable modelers to gain insight into (models of) gene regulation, and generate testable predictions. We introduce a range of modeling frameworks, but focus on ordinary differential equation (ODE) models since they remain the most widely used approach in systems biology and medicine and continue to offer great potential. We present methods for the analysis of a single model, comprising applications of standard dynamical systems approaches such as nondimensionalization, steady state, asymptotic and sensitivity analysis, and more recent statistical and algebraic approaches to compare models with data. We present parameter estimation and model comparison techniques, focusing on Bayesian analysis and coplanarity via algebraic geometry. Our intention is that this (non exhaustive) review may serve as a useful starting point for the analysis of models in systems medicine.Comment: Submitted to 'Systems Medicine' as a book chapte

Multinational perspectives on information technology from academia and industry

As the term \u27information technology\u27 has many meanings for various stakeholders and continues to evolve, this work presents a comprehensive approach for developing curriculum guidelines for rigorous, high quality, bachelor\u27s degree programs in information technology (IT) to prepare successful graduates for a future global technological society. The aim is to address three research questions in the context of IT concerning (1) the educational frameworks relevant for academics and students of IT, (2) the pathways into IT programs, and (3) graduates\u27 preparation for meeting future technologies. The analysis of current trends comes from survey data of IT faculty members and professional IT industry leaders. With these analyses, the IT Model Curricula of CC2005, IT2008, IT2017, extensive literature review, and the multinational insights of the authors into the status of IT, this paper presents a comprehensive overview and discussion of future directions of global IT education toward 2025

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

Sparse visual models for biologically inspired sensorimotor control

Given the importance of using resources efficiently in the competition for survival, it is reasonable to think that natural evolution has discovered efficient cortical coding strategies for representing natural visual information. Sparse representations have intrinsic advantages in terms of fault-tolerance and low-power consumption potential, and can therefore be attractive for robot sensorimotor control with powerful dispositions for decision-making. Inspired by the mammalian brain and its visual ventral pathway, we present in this paper a hierarchical sparse coding network architecture that extracts visual features for use in sensorimotor control. Testing with natural images demonstrates that this sparse coding facilitates processing and learning in subsequent layers. Previous studies have shown how the responses of complex cells could be sparsely represented by a higher-order neural layer. Here we extend sparse coding in each network layer, showing that detailed modeling of earlier stages in the visual pathway enhances the characteristics of the receptive fields developed in subsequent stages. The yield network is more dynamic with richer and more biologically plausible input and output representation

A pathway to independence : wayfinding systems which adapt to a visually impaired person's context

Despite an increased amount of technologies and systems designed to address the navigational requirements of the visually impaired community of approximately 7.4 million in Europe, current research has failed to sufficiently address the human issues associated to their design and use. As more types of sensing technologies are developed to facilitate visually impaired travellers for different navigational purposes (local vs. distant and indoor vs. outdoor), an effective process of synchronisation is required. This synchronisation is represented through context-aware computing, which allows contextual information to not just be sensed (like most current wayfinding systems), but also adapted, discovered and augmented. In this paper, three user studies concerning the suitability of different types of navigational information for visually impaired and sighted people are described. For such systems to be effective, human cognitive maps, models and intentions need to be the focus of further research, in order to provide information that is tailored to a user's task, situation or environment. Methodologies aimed at establishing these issues need to be demonstrated through a multidisciplinary framework

An introduction to Biomodel engineering, illustrated for signal transduction pathways

BioModel Engineering is the science of designing, constructing and analyzing computational models of biological systems. It is inspired by concepts from software engineering and computing science. This paper illustrates a major theme in BioModel Engineering, namely that identifying a quantitative model of a dynamic system means building the structure, finding an initial state, and parameter fitting. In our approach, the structure is obtained by piecewise construction of models from modular parts, the initial state is obtained by analysis of the structure and parameter fitting comprises determining the rate parameters of the kinetic equations. We illustrate this with an example in the area of intracellular signalling pathways

EVALUATION OF PLC PROGRAMME PROVISION. ESRI RESEARCH SERIES NUMBER 61 JANUARY 2018

Post-Leaving Certificate (PLC) courses represent the largest component of full-time further education and training (FET) provision in Ireland, with over 32,000 learners enrolled in such courses in 2015–2016. Recent research on the FET sector as a whole highlighted concerns around its structures and responsiveness to labour market conditions, among other issues (McGuinness et al., 2014). The SOLAS FET Strategy (2014) subsequently pointed to the need for a stronger evidence base in order to inform future policy development in the sector. This study, commissioned by SOLAS, provides a more detailed evaluation of PLC provision. In order to undertake a comprehensive evaluation, our approach has been to combine a variety of research modes in order to examine the underlying processes, experiences and outcomes of PLC provision. This involved three complementary research strands. Firstly, a desk-based analysis of administrative data was used to document the type of provision in terms of field of study and the distribution of PLC places across the country. Secondly, a survey of PLC principals was carried out in order to explore their perceptions of goals, adequacy of existing facilities and the benefits and challenges of PLC provision. Thirdly, a survey of PLC and Leaving Certificate leavers was conducted to assess their labour market outcomes as well as their experiences while taking PLC and higher education courses. Together, these strands provide comprehensive evidence to inform the future development of the sector