Insights into the behaviour of systems biology models from dynamic sensitivity and identifiability analysis: a case study of an NF-kB signaling pathway

Mathematical modelling offers a variety of useful techniques to help in understanding the intrinsic behaviour of complex signal transduction networks. From the system engineering point of view, the dynamics of metabolic and signal transduction models can always be described by nonlinear ordinary differential equations (ODEs) following mass balance principles. Based on the state-space formulation, many methods from the area of automatic control can conveniently be applied to the modelling, analysis and design of cell networks. In the present study, dynamic sensitivity analysis is performed on a model of the IB-NF-B signal pathway system. Univariate analysis of the Euclidean-form overall sensitivities shows that only 8 out of the 64 parameters in the model have major influence on the nuclear NF-B oscillations. The sensitivity matrix is then used to address correlation analysis, identifiability assessment and measurement set selection within the framework of least squares estimation and multivariate analysis. It is shown that certain pairs of parameters are exactly or highly correlated to each other in terms of their effects on the measured variables. The experimental design strategy provides guidance on which proteins should best be considered for measurement such that the unknown parameters can be estimated with the best statistical precision. The whole analysis scheme we describe provides efficient parameter estimation techniques for complex cell networks

Input variable selection in time-critical knowledge integration applications: A review, analysis, and recommendation paper

This is the post-print version of the final paper published in Advanced Engineering Informatics. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2013 Elsevier B.V.The purpose of this research is twofold: first, to undertake a thorough appraisal of existing Input Variable Selection (IVS) methods within the context of time-critical and computation resource-limited dimensionality reduction problems; second, to demonstrate improvements to, and the application of, a recently proposed time-critical sensitivity analysis method called EventTracker to an environment science industrial use-case, i.e., sub-surface drilling. Producing time-critical accurate knowledge about the state of a system (effect) under computational and data acquisition (cause) constraints is a major challenge, especially if the knowledge required is critical to the system operation where the safety of operators or integrity of costly equipment is at stake. Understanding and interpreting, a chain of interrelated events, predicted or unpredicted, that may or may not result in a specific state of the system, is the core challenge of this research. The main objective is then to identify which set of input data signals has a significant impact on the set of system state information (i.e. output). Through a cause-effect analysis technique, the proposed technique supports the filtering of unsolicited data that can otherwise clog up the communication and computational capabilities of a standard supervisory control and data acquisition system. The paper analyzes the performance of input variable selection techniques from a series of perspectives. It then expands the categorization and assessment of sensitivity analysis methods in a structured framework that takes into account the relationship between inputs and outputs, the nature of their time series, and the computational effort required. The outcome of this analysis is that established methods have a limited suitability for use by time-critical variable selection applications. By way of a geological drilling monitoring scenario, the suitability of the proposed EventTracker Sensitivity Analysis method for use in high volume and time critical input variable selection problems is demonstrated.E

A decision support system based on Electre III for safety analysis in a suburban road network

The aim of this paper is to develop a method for supporting decision makers in transport planning. When funds are insufficient to cover the interventions required to ensure safe driving conditions, it is necessary to optimize resources for the most critical sections. In this analysis, the multicriteria ranking method based on the ELECTRE III algorithms is applied to a real case, involving different sections of a motorway. This analysis is based on a comparison of different road sections in regard to safety conditions. The rank of more critical sections identifies intervention priorities

Higher Education Outcomes, Graduate Employment and University Performance Indicators

Official employment-related Performance Indicators in UK Higher Education are based on the population of students responding to the First Destination Supplement (FDS). This generates potentially biased performance indicators as this population of students is not necessarily representative of the full population of leavers from each institution. University leavers not obtaining qualifications and those not responding to the FDS are not included within the official analysis. We compare an employment-related performance indicator based on those students responding to the FDS with alternative approaches which address the potential non-random nature of this sub-group of university leavers.Employment ; higher education ; performance indicators ; nonrandom response

Multicriteria rankings of open-end investment funds and their stability

For research purposes, three multicriteria outranking methods (PROMETHEE, WSA and TOPSIS) were used to construct rankings of investment funds to assess their performance in the time period from January to July 2008. Nine indicators related to the distributions of return rates, purchase and management costs and to customers’ convenience were included in the set of criteria. The weight of each criterion was calculated on the basis of the relative volatility rate of the given criterion. In order to assess the stability of the rankings, the weight of a single criterion was changed (using each criterion in turn) and new rankings were constructed using the modified weights. The similarity of rankings built before and after these changes was assessed on the basis of the maximum difference between ranks and the Spearman correlation coefficient. The results obtained enable assessment not only of the stability of each outranking method, but the similarity of results obtained by different methods as well. All calculations were done using the SANNA software.investment funds, outranking methods, PROMETHEE method, WSA method, TOPSIS method, stability of rankings