Uncertainty quantification and global sensitivity analysis for economic models

Dimensionality reduction for surrogate model construction for global sensitivity analysis: Comparison between active subspace and local sensitivity analysis

The main focus of this thesis is the uncertainty propagation (UP) and global sensitivity analysis (GSA) in complex hydrogeological numerical models. Various methods are presented with applications on numerical models for the groundwater flow and mean lifetime expectancy (MLE) in the scope of Andra's (French National Radioactive Waste Management Agency) project for the geological disposal of high-level and intermediate-level long-lived radioactive wastes in a highly impermeable layer from Callovo-Oxfordian age (COX) in France. <br> A state of the art is provided for the theory of uncertainty propagation and for the methodologies of sensitivity analyses in a broad sense. Methods for UP are provided from 2-levels Factorial Designs to quasi-random samplings. GSA techniques encompass screening methods such as the Morris Measures and the Derivative-based Global Sensitivity Measures (DGSM), and also the so-called Sobol' indices based upon the variance decomposition of the response of interest. Meta-modelling techniques such as polynomial regression and Polynomial Chaos Expansions (PCE) meta-models are employed as surrogate models for UP and GSA purpose at negligible computational-costs. A comparison of GSA techniques upon various complex analytical test-functions was undertaken with the purpose of determining a relevant method to be employed in the context of “screening” out unimportant variables in computer-intensive, high-dimensional models. <br> A numerical model of groundwater flow and lifetime expectancy is employed for assessing the effect of uncertain advection-dispersion parameters and their spatial distributions upon the MLE from a target zone inside the domain. The model is a 2-dimensions synthetic cross-section of the eastern region of the Paris Basin (Meuse/Haute-Marne sector). This model was used as an exploratory tool for sensitivity analysis methods applied upon numerous sets of uncertain hydrodynamic and dispersion parameters in 15 layers. The uncertainty characterizing the permeability-porosity values in aquifer formations encompassing the COX have proved to add much of variability to the MLE calculated from the target zone. The model also served at exploring the effect of the spatial variability of permeability-porosity parameters in two main aquifer sequences on the groundwater flow rates and MLE in the model. The variabilities of the output responses are mainly due to the uncertainty upon the means and variances of the permeability-porosity distributions, as well as the longitudinal correlation lengths, in each sequence. <br> Then, a 3-dimensions high-definition hydrogeological model representing the Meuse/Haute-Marne sector in the eastern region of the Paris Basin is a more comprehensive numerical model incorporating realistic geometries, fractures, heterogeneities and discontinuities encountered on field. A sensitivity analysis of the MLE from a given zone located in the middle of the COX layer was performed by perturbing the hydraulic conductivities and porosities values in fourteen hydrogeological formations. The uncertain permeability-porosity parameters in the aquifer formations from Bathonian in the Dogger sequence, and Rauracian-Sequanian in the Oxfordian sequence, have strong and rather non-linear effects on the variability of the output response of interest. <br> The methodologies for UP and GSA employed in the present thesis have proved to be very efficient when applied to large hydrogeological models of groundwater flow and MLE. In particular, quasi-random sampling methods offer a flexible frame for providing the uncertainty distribution of the output response of interest at low computational costs. Screening techniques provide a fast estimation for the overall contribution of each input variable to the variability of the output. Meta-modelling techniques such as PCE proved highly accurate in individualising the low- and high-order effects of each input variable upon the output response of interest.

Global sensitivity analysis: A Bayesian learning based polynomial chaos approach

Performing uncertainty quantification (UQ) and sensitivity analysis (SA) is vital when developing a patient-specific physiological model because it can quantify model output uncertainty and estimate the effect of each of the model's input parameters on the mathematical model. By providing this information, UQ and SA act as diagnostic tools to evaluate model fidelity and compare model characteristics with expert knowledge and real world observation. Computational efficiency is an important part of UQ and SA methods and thus optimization is an active area of research. In this work, we investigate a new efficient sampling method for least-squares polynomial approximation, weighted approximate Fekete points (WAFP). We analyze the performance of this method by demonstrating its utility in stochastic analysis of a cardiovascular model that estimates changes in oxyhemoglobin saturation response. Polynomial chaos (PC) expansion using WAFP produced results similar to the more standard Monte Carlo in quantifying uncertainty and identifying the most influential model inputs (including input interactions) when modeling oxyhemoglobin saturation, PC expansion using WAFP was far more efficient. These findings show the usefulness of using WAFP based PC expansion to quantify uncertainty and analyze sensitivity of a oxyhemoglobin dissociation response model. Applying these techniques could help analyze the fidelity of other relevant models in preparation for clinical application.

There is uncertainty in the results of any mathematical model due to different reasons. It is important to estimate this uncertainty. Sensitivity analysis is commonly used to estimate how the changes in the input parameters affect the solutions of the model. In this paper, we discuss different ways of performing local and global sensitivity analyses and apply them to two models: an epidemic model and a new myocardial infarction model, both based on ordinary differential equations. The first model is a simple model used to explain the ideas, while the second one shows how to apply them to a model with more state variables and parameters. We find that if the parameters are not accurately known, local sensitivity analysis can be misleading and that global sensitivity methods that sample the whole parameter space, varying all the values of the parameters at the same time, are the most reliable. We also show how the sensitivity analysis results can be used to determine the uncertainty in the results of the model. We present numerical simulations.

In this study, a hybrid metamodel using the orthogonal constraints of radial basis function and sparse polynomial chaos expansions is proposed for the global sensitivity analysis of time-consuming models. Firstly, the orthogonal conditions of radial basis functions (RBF) and polynomial chaos expansions (PCE) were derived to construct the hybrid metamodel. Then, the variance of the metamodel was decoupled into the variances of the RBF and PCE independently by using the orthogonal condition. Furthermore, the analytical formulations of Sobol indices for the hybrid metamodel were derived according to the orthogonal decomposition. Thus, the interaction items of radial basis function and polynomial chaos expansions were eliminated, which significantly simplifies the Sobol indices. Two analytical cases were employed to investigate the influence of the number of the polynomial chaos expansions items, and several analytical and engineering cases were tested to demonstrate the accuracy and efficiency of the proposed method. In the engineering cases, the proposed method yielded significant improvements in terms of both accuracy and efficiency comparing with the existing global sensitivity analysis approaches, which indicates that the proposed method is more appropriate to the global sensitivity analysis of time-consuming engineering problems.

Global Sensitivity Analysis of Arrhythmic Risk Biomarkers in Cardiac Single Cell Models

Adaptive sparse polynomial chaos expansions for global sensitivity analysis based on support vector regression

Recent efforts to ensure the reliability of computational model-based predictions in healthcare, such as the ASME V&V40 Standard, emphasize the importance of uncertainty quantification (UQ) and sensitivity analysis (SA) when evaluating computational models. UQ involves empirically determining the uncertainty in model inputs—typically resulting from natural variability or measurement error—and then calculating the resultant uncertainty in model outputs. SA involves calculating how uncertainty in model outputs can be apportioned to input uncertainty. Rigorous comprehensive UQ/SA provides confidence that model-based decisions are robust to underlying uncertainties. However, comprehensive UQ/SA is not currently feasible for whole heart models, due to numerous factors including model complexity and difficulty in measuring variability in the many parameters. Here, we present a significant step to developing a framework to overcome these limitations. We: (i) developed a novel action potential (AP) model of moderate complexity (six currents, seven variables, 36 parameters); (ii) prescribed input variability for all parameters (not empirically derived); (iii) used a single “hyper-parameter” to study increasing levels of parameter uncertainty; (iv) performed UQ and SA for a range of model-derived quantities with physiological relevance; and (v) present quantitative and qualitative ways to analyze different behaviors that occur under parameter uncertainty, including “model failure”. This is the first time uncertainty in every parameter (including conductances, steady-state parameters, and time constant parameters) of every ionic current in a cardiac model has been studied. This approach allowed us to demonstrate that, for this model, the simulated AP is fully robust to low levels of parameter uncertainty — to our knowledge the first time this has been shown of any cardiac model. A range of dynamics was observed at larger parameter uncertainty (e.g., oscillatory dynamics); analysis revealed that five parameters were highly influential in these dynamics. Overall, we demonstrate feasibility of performing comprehensive UQ/SA for cardiac cell models and demonstrate how to assess robustness and overcome model failure when performing cardiac UQ analyses. The approach presented here represents an important and significant step toward the development of model-based clinical tools which are demonstrably robust to all underlying uncertainties and therefore more reliable in safety-critical decision-making.

Event Abstract Back to Event Statistical uncertainty and sensitivity analysis of intracellular signaling models - through approximate Bayesian computation and variance based global sensitivity analysis Olivia Eriksson1, 2*, Alexandra Jauhiainen1, 3, Sara Maad Sasane4, Anu G Nair5, Carolina Sartorius4 and Jeanette Hellgren Kotaleski2, 5, 6 1 Contributed equally to this work, Sweden 2 Stockholm University, Department of Numerical Analysis and Computer Science, Sweden 3 AstraZeneca AB R&D, Early Clinical Biometrics, Sweden 4 Lund University, Centre for Mathematical Sciences, Sweden 5 KTH Royal Institute of Technology, School of Computer Science and Communication, Sweden 6 Karolinska Institute, Department of Neuroscience, Sweden Computational dynamical models describing intracellular signaling pathways of nerve cells are increasing in size and complexity as more information is obtained from experiments. Models describing protein interactions within neurons can contain over hundred protein reactions [1, 2]. These models are built from knowledge about the interaction topology, inferred from e.g. gene knock-out experiments, as well as from experimental quantitative data describing the input-output relationship of the observed system. The quantitative data are often sparse as compared to the size of the system, and translating the experimental information into dynamical models often results in large uncertainties in the parameter (e.g reaction rates) values. This uncertainty is partly due to the sparseness in experimental time series data (practical unidentifiability), but it is also an intrinsic feature of the modeled system (structural unidentifiability) and could reflect the possibility for biological variation [3]; in many biological systems the same function can be achieved in partly different ways due to degeneracy and redundancy. Here we investigate the extent of this parameter uncertainty, in a model describing calcium (Ca)-dependent activation of Calmodulin (CaM), Protein phosphatase 2B (PP2B) and Ca/CaM-dependent protein kinase II (CamKII) [4], which is an intracellular pathway of importance to synaptic plasticity. We presume that the structure of the model is correct and then characterize the uncertainty in the parameters based on data. This is done by sampling the subspace of parameter values which has an equally good fit to data (corresponding to the “viable space” in [5]), through a statistical approach known as Approximate Bayesian Computation (ABC) with Markov Chain Monte Carlo (MCMC) [6]. ABC has been proposed for parameter estimation in system biology models previously, albeit in slightly different settings, e.g. [7, 8], and can be applied to a wide range of problems. In order to characterize the viable space efficiently with several experimental datasets, we employ multivariate probability distributions called copulas as a part of the ABC sampling. The result is a multivariate posterior distribution for the parameters, which represents how much they are constrained by the data (i.e. the uncertainty) as illustrated in Figure 1 (pairwise plots of viable space for four parameters indicating constraints and dependencies before and after calibration to data). The next step is to look into how the parameter uncertainty is translated to uncertainty of the predictions made from the model. We also investigate the role and importance of different parameters, with respect to different model outputs including the predictions, by means of global sensitivity analysis [9]. Figure 2 illustrates the sensitivity of one of the outputs calculated by a method based on the decomposition of the variance [10, 11, 12], showing different types of sensitivity measures. Finally, we explore how the sensitivity of different subsets of parameters change as different parts of the viable space are investigated, which is shown in Figure 3, where sensitivity profiles are clustered into groups with different sensitivity characteristics. Figure 1 Figure 2 Figure 3 Acknowledgements This research was supported by funding from the Swedish e-Science Research Centre and the Human Brain Project References [1] Gutierrez-Arenas O, Eriksson O, Hellgren Kotaleski J (2014) Segregation and Crosstalk of D1 Receptor-Mediated Activation of ERK in Striatal Medium Spiny Neurons upon Acute Administration of Psychostimulants. PLoS Comput Biol 10, e1003445. [2] Nair AG, Gutierrez-Arenas O, Eriksson O, Vincent P, and Hellgren Kotaleski J (2015) Sensing Positive versus Negative Reward Signals through Adenylyl Cyclase-Coupled GPCRs in Direct and Indirect Pathway Striatal Medium Spiny Neurons. J. Neuroscience 35, 14017-14030. [3] Marder E, Goeritz ML, Otopalik AG (2015) Robust circuit rhythms in small circuits arise from variable circuit components and mechanisms. Curr Opin Neurobiol 31, 156-163. [4] Nair AG, Gutierrez-Arenas O, Eriksson O, Jauhiainen A, Blackwell KT and Kotaleski, JH (2014). Modeling intracellular signaling underlying striatal function in health and disease. Progress in molecular biology and translational science, 123, 277 [5] Zamora-Sillero E, Hafner M, Ibig A, Stelling J, and Wagner, A. (2011). Efficient characterization of high-dimensional parameter spaces for systems biology. BMC systems biology 5, 142. [6] Marjoram P, Molitor J, Plagnol V, and Tavare S (2003) Markov chain Monte Carlo without likelihoods. Proc. Natl. Acad. Sci. U.S.A. 100, 15324–15328. [7] Toni T, Welch D, Strelkowa N, Ipsen A, and Stumpf MP. Approximate Bayesian computation scheme for parameter inference and model selection in dynamical systems. J R Soc Interface, 6, 187–202. [8] Liepe J, Kirk P, Filippi S, Toni T, Barnes CP, and Stumpf MP. A framework for parameter estimation and model selection from experimental data in systems biology using approximate Bayesian computation. Nat Protoc, 9, 439–456. [9] Saltelli A, Ratto M, Andres T, Campolongo F, Cariboni J, Gatelli D, Saisana M, Tarantola S Global sensitivity analysis: the primer. In Wiley 2008 New York, NY:Wiley. [10] Sobol IM (2001) Global sensitivity indices for nonlinear mathematical models and their Monte Carlo estimates, Math. Comput. Simul. 55, 271–280. [11] Saltelli A (2002) Making best use of model evaluations to compute sensitivity indices. Comp Phys Comm 145, 280 – 297. [12] Halnes G, Ulfhielm E Ljunggren EE, Kotaleski JH and Rospars JP (2009) Modelling and sensitivity analysis of the reactions involving receptor, G-protein and effector in vertebrate olfactory receptor neurons. Journal of computational neuroscience 27, 471-491. Keywords: sensitivity analysis, Approximate Bayesian Computation, copulas, intracellular signalling, Dynamical Modeling, global sensitivity analysis, Markov chain Monte Carlo, variance decomposition Conference: Neuroinformatics 2016, Reading, United Kingdom, 3 Sep - 4 Sep, 2016. Presentation Type: Investigator presentations Topic: Computational neuroscience Citation: Eriksson O, Jauhiainen A, Maad Sasane S, Nair A, Sartorius C and Hellgren Kotaleski J (2016). Statistical uncertainty and sensitivity analysis of intracellular signaling models - through approximate Bayesian computation and variance based global sensitivity analysis. Front. Neuroinform. Conference Abstract: Neuroinformatics 2016. doi: 10.3389/conf.fninf.2016.20.00014 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 31 May 2016; Published Online: 18 Jul 2016. * Correspondence: PhD. Olivia Eriksson, Contributed equally to this work, Stockholm, Sweden, olivia@kth.se Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Olivia Eriksson Alexandra Jauhiainen Sara Maad Sasane Anu G Nair Carolina Sartorius Jeanette Hellgren Kotaleski Google Olivia Eriksson Alexandra Jauhiainen Sara Maad Sasane Anu G Nair Carolina Sartorius Jeanette Hellgren Kotaleski Google Scholar Olivia Eriksson Alexandra Jauhiainen Sara Maad Sasane Anu G Nair Carolina Sartorius Jeanette Hellgren Kotaleski PubMed Olivia Eriksson Alexandra Jauhiainen Sara Maad Sasane Anu G Nair Carolina Sartorius Jeanette Hellgren Kotaleski Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Sensitivity analyses are frequently used during the design of engineering systems to qualify and quantify the effect of parametric variation in the performance of a system. Two primary types of sensitivity analyses are generally used: local and global. Local analyses, generally involving derivative-based measures, have a significantly lower computational burden than global analyses but only provide measures of sensitivity around a nominal point. Global analyses, generally performed with a Monte Carlo sampling approach, and variation-based measures provide a complete description of sensitivity but incur a large computational burden and require information regarding the distributions of the design parameters in a concept. Local analyses are generally suited to the early stages of design when parametric information is limited, and a large number of concepts must be evaluated (necessitating a light computational burden). Global analyses are more suited to the later stages of design when more information about parametric distributions is available and fewer concepts are under consideration. Current derivative-based local approaches provide a different and incompatible set of measures than a global variation-based analysis. This makes a direct comparison of local to global measures ill posed. To reconcile local and global sensitivity analyses, a hybrid local variation-based sensitivity (HyVar) approach is presented. This approach has a similar computational burden to a local approach but produces measures or percentage contributions. The HyVar approach is directly comparable to global variation-based approaches. In this paper, the HyVar sensitivity analysis method is developed in the context of a functional based behavioral modeling framework. An example application of the method is presented along with a summary of results produced from a more comprehensive example.

ABSTRACTPROSAIL is a combination of the leaf optical properties spectra (PROSPECT) model and the scattering by arbitrarily inclined leaves (SAIL) canopy bidirectional reflectance model. When modelling forest canopy reflectance using the PROSAIL radiative transfer model, the sensitivities of parameters can affect the modelling accuracy. Traditionally, sensitivities have been assessed using local sensitivity analysis (LSA); however, drawbacks to this approach include a lack of consideration for coupled effects between different parameters. In this study, parameter sensitivities in the PROSAIL model were calculated using two global sensitivity analysis (GSA) methods (the Extended Fourier Amplitude Sensitivity Test (EFAST) method and the Morris method), field measurements, and Landsat 5 Thematic Mapper (TM) data for a Moso bamboo forest. The results of GSA were compared with those of LSA in order to identify the key parameters impacting the Moso bamboo forest canopy reflectance, and to provide a reference for model optimization and vegetation canopy inversion improvement. The results showed that: (1) the sensitivities of six major input parameters of the PROSAIL model were generally consistent with the sorting orders of the two GSA methods, but were not in accordance with those from the LSA method, especially in the mid-infrared band; (2) coupled effects among parameters acting on reflectance simulation in visible light bands were greater than those in infrared bands; (3) the simulated canopy reflectance was evaluated using Landsat 5 TM data, and the results simulated based on LSA analysis showed higher error than those based on GSA analysis, because the LSA method ignored the influence of some parameters on canopy reflectance, e.g. leaf mesophyll structure (N), average leaf angle (ALA), leaf water content (Cw), and leaf dry matter content (Cm). However, GSA was able to fully consider the coupled effects among parameters, and thus identified the sensitive parameters impacting on reflectance more accurately.

In this paper, we study the dynamical effects of timely and delayed diagnosis on the spread of COVID-19 in Ghana during its initial phase by using reported data from March 12 to June 19, 2020. The estimated basic reproduction number, ℛ0, for the proposed model is 1.04. One of the main focus of this study is global stability results. Theoretically and numerically, we show that the disease persistence depends on ℛ0. We carry out a local and global sensitivity analysis. The local sensitivity analysis shows that the most positive sensitive parameter is the recruitment rate, followed by the relative transmissibility rate from the infectious with delayed diagnosis to the susceptible individuals. And that the most negative sensitive parameters are: self-quarantined, waiting time of the infectious for delayed diagnosis and the proportion of the infectious with timely diagnosis. The global sensitivity analysis using the partial rank correlation coefficient confirms the directional flow of the local sensitivity analysis. For public health benefit, our analysis suggests that, a reduction in the inflow of new individuals into the country or a reduction in the inter community inflow of individuals will reduce the basic reproduction number and thereby reduce the number of secondary infections (multiple peaks of the infection). Other recommendations for controlling the disease from the proposed model are provided in Section 7.

Quantification of the uncertainty in constitutive model predictions describing arterial wall mechanics is vital towards non-invasive assessment of vascular drug therapies. Therefore, we perform uncertainty quantification to determine uncertainty in mechanical characteristics describing the vessel wall response upon loading. Furthermore, a global variance-based sensitivity analysis is performed to pinpoint measurements that are most rewarding to be measured more precisely. We used previously published carotid diameter–pressure and intima–media thickness (IMT) data (measured in triplicate), and Holzapfel–Gasser–Ogden models. A virtual data set containing 5000 diastolic and systolic diameter–pressure points, and IMT values was generated by adding measurement error to the average of the measured data. The model was fitted to single-exponential curves calculated from the data, obtaining distributions of constitutive parameters and constituent load bearing parameters. Additionally, we (1) simulated vascular drug treatment to assess the relevance of model uncertainty and (2) evaluated how increasing the number of measurement repetitions influences model uncertainty. We found substantial uncertainty in constitutive parameters. Simulating vascular drug treatment predicted a 6% point reduction in collagen load bearing (L_mathrm {coll}), approximately 50% of its uncertainty. Sensitivity analysis indicated that the uncertainty in L_{mathrm {coll}} was primarily caused by noise in distension and IMT measurements. Spread in L_{mathrm {coll}} could be decreased by 50% when increasing the number of measurement repetitions from 3 to 10. Model uncertainty, notably that in L_{mathrm {coll}}, could conceal effects of vascular drug therapy. However, this uncertainty could be reduced by increasing the number of measurement repetitions of distension and wall thickness measurements used for model parameterisation.

Sensitivity analysis and calibration of phenomenological models for seismic analyses