Challenges in horizontal model integration

BACKGROUND: Systems Biology has motivated dynamic models of important intracellular processes at the pathway level, for example, in signal transduction and cell cycle control. To answer important biomedical questions, however, one has to go beyond the study of isolated pathways towards the joint study of interacting signaling pathways or the joint study of signal transduction and cell cycle control. Thereby the reuse of established models is preferable, as it will generally reduce the modeling effort and increase the acceptance of the combined model in the field. RESULTS: Obtaining a combined model can be challenging, especially if the submodels are large and/or come from different working groups (as is generally the case, when models stored in established repositories are used). To support this task, we describe a semi-automatic workflow based on established software tools. In particular, two frequent challenges are described: identification of the overlap and subsequent (re)parameterization of the integrated model. CONCLUSIONS: The reparameterization step is crucial, if the goal is to obtain a model that can reproduce the data explained by the individual models. For demonstration purposes we apply our workflow to integrate two signaling pathways (EGF and NGF) from the BioModels Database. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12918-016-0266-3) contains supplementary material, which is available to authorized users

Prognostic Methods for Integrating Data from Complex Diseases

Statistics in medical research gained a vast surge with the development of high-throughput biotechnologies that provide thousands of measurements for each patient. These multi-layered data has the clear potential to improve the disease prognosis. Data integration is increasingly becoming essential in this context, to address problems such as increasing the power, inconsistencies between studies, obtaining more reliable biomarkers and gaining a broader understanding of the disease. This thesis focuses on addressing the challenges in the development of statistical methods while contributing to the methodological advancements in this field. We propose a clinical data analysis framework to obtain a model with good prediction accuracy addressing missing data and model instability. A detailed pre-processing pipeline is proposed for miRNA data that removes unwanted noise and offers improved concordance with qRT-PCR data. Platform specific models are developed to uncover biomarkers using mRNA, protein and miRNA data, to identify the source with the most important prognostic information. This thesis explores two types of data integration: horizontal; the integration of same type of data, and vertical; the integration of data from different platforms for the same patient. We use multiple miRNA datasets to develop a meta-analysis framework addressing the challenges in horizontal data integration using a multi-step validation protocol. In the vertical data integration, we extend the pre-validation principle and derive platform dependent weights to utilise the weighted Lasso. Our study revealed that integration of multi-layered data is instrumental in improving the prediction accuracy and in obtaining more biologically relevant biomarkers. A novel visualisation technique to look at prediction accuracy at patient level revealed vital findings with translational impact in personalised medicine

A leadership model for e-government transformation

Since the late 1990’s governments have invested aggressively in Information and Communications Technology (ICT). This trend has paved the way for moving into the “Digital Age”. However, despite the wide use of ICT, research on e-government suggests that it has not yet reached its full potential of integration. In this paper the authors consider possible reasons for this potential shortfall, using models of adoption of innovations and relating them to egovernment. In doing so, a simple “Leadership Model” is proposed, that will lead to a profound understanding in transforming government and widen the agenda for further research. In particular, the aim of this paper is to highlight and explain of the gap that exist in the final stage of multi-stage-government maturity model by (Layne and Lee, 2001) and what is needed to overcome i

Transaction stage of e-Government systems: identification of its location & importance

All e-Government maturity models identify a Transaction stage along the pathway to full systems integration. The evidence suggests that a significant number of project failures occur at this stage and thus frustrate the endeavour to achieve a coherent uniform means of access to Government. Clearly, research to identify and overcome the challenges presented at this stage is critical. In this paper the Transaction stage is clearly delineated as the point at which online technology ceases to be peripheral to the agency’s activity. Hence, it presents the first real organisational challenge and an appropriate research strategy is defined to uncover the problems that arise at this point

Online service delivery models : an international comparison in the public sector

Governments around the world are facing the challenge of responding to increased expectations by their customers with regard to public service delivery. Citizens, for example, expect governments to provide better and more efficient electronic services on the Web in an integrated way. Online portals have become the approach of choice in online service delivery to meet these requirements and become more customer-focussed. This study describes and analyses existing variants of online service delivery models based upon an empirical study and provides valuable insights for researchers and practitioners in government. For this study, we have conducted interviews with senior management representatives from five international governments. Based on our findings, we distinguish three different classes of service delivery models. We describe and characterise each of these models in detail and provide an in-depth discussion of the strengths and weaknesses of these approaches

A survey of carbon nanotube interconnects for energy efficient integrated circuits

This article is a review of the state-of-art carbon nanotube interconnects for Silicon application with respect to the recent literature. Amongst all the research on carbon nanotube interconnects, those discussed here cover 1) challenges with current copper interconnects, 2) process & growth of carbon nanotube interconnects compatible with back-end-of-line integration, and 3) modeling and simulation for circuit-level benchmarking and performance prediction. The focus is on the evolution of carbon nanotube interconnects from the process, theoretical modeling, and experimental characterization to on-chip interconnect applications. We provide an overview of the current advancements on carbon nanotube interconnects and also regarding the prospects for designing energy efficient integrated circuits. Each selected category is presented in an accessible manner aiming to serve as a survey and informative cornerstone on carbon nanotube interconnects relevant to students and scientists belonging to a range of fields from physics, processing to circuit design

Integration of decision support systems to improve decision support performance

Decision support system (DSS) is a well-established research and development area. Traditional isolated, stand-alone DSS has been recently facing new challenges. In order to improve the performance of DSS to meet the challenges, research has been actively carried out to develop integrated decision support systems (IDSS). This paper reviews the current research efforts with regard to the development of IDSS. The focus of the paper is on the integration aspect for IDSS through multiple perspectives, and the technologies that support this integration. More than 100 papers and software systems are discussed. Current research efforts and the development status of IDSS are explained, compared and classified. In addition, future trends and challenges in integration are outlined. The paper concludes that by addressing integration, better support will be provided to decision makers, with the expectation of both better decisions and improved decision making processes