2,476 research outputs found
Observability and Structural Identifiability of Nonlinear Biological Systems
Observability is a modelling property that describes the possibility of
inferring the internal state of a system from observations of its output. A
related property, structural identifiability, refers to the theoretical
possibility of determining the parameter values from the output. In fact,
structural identifiability becomes a particular case of observability if the
parameters are considered as constant state variables. It is possible to
simultaneously analyse the observability and structural identifiability of a
model using the conceptual tools of differential geometry. Many complex
biological processes can be described by systems of nonlinear ordinary
differential equations, and can therefore be analysed with this approach. The
purpose of this review article is threefold: (I) to serve as a tutorial on
observability and structural identifiability of nonlinear systems, using the
differential geometry approach for their analysis; (II) to review recent
advances in the field; and (III) to identify open problems and suggest new
avenues for research in this area.Comment: Accepted for publication in the special issue "Computational Methods
for Identification and Modelling of Complex Biological Systems" of Complexit
Identifiability and Unmixing of Latent Parse Trees
This paper explores unsupervised learning of parsing models along two
directions. First, which models are identifiable from infinite data? We use a
general technique for numerically checking identifiability based on the rank of
a Jacobian matrix, and apply it to several standard constituency and dependency
parsing models. Second, for identifiable models, how do we estimate the
parameters efficiently? EM suffers from local optima, while recent work using
spectral methods cannot be directly applied since the topology of the parse
tree varies across sentences. We develop a strategy, unmixing, which deals with
this additional complexity for restricted classes of parsing models
An Alternative Approach to Functional Linear Partial Quantile Regression
We have previously proposed the partial quantile regression (PQR) prediction
procedure for functional linear model by using partial quantile covariance
techniques and developed the simple partial quantile regression (SIMPQR)
algorithm to efficiently extract PQR basis for estimating functional
coefficients. However, although the PQR approach is considered as an attractive
alternative to projections onto the principal component basis, there are
certain limitations to uncovering the corresponding asymptotic properties
mainly because of its iterative nature and the non-differentiability of the
quantile loss function. In this article, we propose and implement an
alternative formulation of partial quantile regression (APQR) for functional
linear model by using block relaxation method and finite smoothing techniques.
The proposed reformulation leads to insightful results and motivates new
theory, demonstrating consistency and establishing convergence rates by
applying advanced techniques from empirical process theory. Two simulations and
two real data from ADHD-200 sample and ADNI are investigated to show the
superiority of our proposed methods
Determining Structurally Identifiable Parameter Combinations Using Subset Profiling
Identifiability is a necessary condition for successful parameter estimation
of dynamic system models. A major component of identifiability analysis is
determining the identifiable parameter combinations, the functional forms for
the dependencies between unidentifiable parameters. Identifiable combinations
can help in model reparameterization and also in determining which parameters
may be experimentally measured to recover model identifiability. Several
numerical approaches to determining identifiability of differential equation
models have been developed, however the question of determining identifiable
combinations remains incompletely addressed. In this paper, we present a new
approach which uses parameter subset selection methods based on the Fisher
Information Matrix, together with the profile likelihood, to effectively
estimate identifiable combinations. We demonstrate this approach on several
example models in pharmacokinetics, cellular biology, and physiology
Structural identifiability of dynamic systems biology models
22 páginas, 5 figuras, 2 tablas.-- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.A powerful way of gaining insight into biological systems is by creating a nonlinear differential equation model, which usually contains many unknown parameters. Such a model is called structurally identifiable if it is possible to determine the values of its parameters from measurements of the model outputs. Structural identifiability is a prerequisite for parameter estimation, and should be assessed before exploiting a model. However, this analysis is seldom performed due to the high computational cost involved in the necessary symbolic calculations, which quickly becomes prohibitive as the problem size increases. In this paper we show how to analyse the structural identifiability of a very general class of nonlinear models by extending methods originally developed for studying observability. We present results about models whose identifiability had not been previously determined, report unidentifiabilities that had not been found before, and show how to modify those unidentifiable models to make them identifiable. This method helps prevent problems caused by lack of identifiability analysis, which can compromise the success of tasks such as experiment design, parameter estimation, and model-based optimization. The procedure is called STRIKE-GOLDD (STRuctural Identifiability taKen as Extended-Generalized Observability with Lie Derivatives and Decomposition), and it is implemented in a MATLAB toolbox which is available as open source software. The broad applicability of this approach facilitates the analysis of the increasingly complex models used in systems biology and other areasAFV acknowledges funding from the Galician government (Xunta de Galiza, Consellería de Cultura, Educación e Ordenación Universitaria http://www.edu.xunta.es/portal/taxonomy/term/206) through the I2C postdoctoral program, fellowship ED481B2014/133-0. AB and AFV were partially supported by grant DPI2013-47100-C2-2-P from the Spanish Ministry of Economy and Competitiveness (MINECO). AFV acknowledges additional funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 686282 (CanPathPro). AP was partially supported through EPSRC projects EP/M002454/1 and EP/J012041/1.Peer reviewe
Identifiability of parameters in latent structure models with many observed variables
While hidden class models of various types arise in many statistical
applications, it is often difficult to establish the identifiability of their
parameters. Focusing on models in which there is some structure of independence
of some of the observed variables conditioned on hidden ones, we demonstrate a
general approach for establishing identifiability utilizing algebraic
arguments. A theorem of J. Kruskal for a simple latent-class model with finite
state space lies at the core of our results, though we apply it to a diverse
set of models. These include mixtures of both finite and nonparametric product
distributions, hidden Markov models and random graph mixture models, and lead
to a number of new results and improvements to old ones. In the parametric
setting, this approach indicates that for such models, the classical definition
of identifiability is typically too strong. Instead generic identifiability
holds, which implies that the set of nonidentifiable parameters has measure
zero, so that parameter inference is still meaningful. In particular, this
sheds light on the properties of finite mixtures of Bernoulli products, which
have been used for decades despite being known to have nonidentifiable
parameters. In the nonparametric setting, we again obtain identifiability only
when certain restrictions are placed on the distributions that are mixed, but
we explicitly describe the conditions.Comment: Published in at http://dx.doi.org/10.1214/09-AOS689 the Annals of
Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical
Statistics (http://www.imstat.org
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