The Parameter Houlihan: a solution to high-throughput identifiability indeterminacy for brutally ill-posed problems

One way to interject knowledge into clinically impactful forecasting is to use data assimilation, a nonlinear regression that projects data onto a mechanistic physiologic model, instead of a set of functions, such as neural networks. Such regressions have an advantage of being useful with particularly sparse, non-stationary clinical data. However, physiological models are often nonlinear and can have many parameters, leading to potential problems with parameter identifiability, or the ability to find a unique set of parameters that minimize forecasting error. The identifiability problems can be minimized or eliminated by reducing the number of parameters estimated, but reducing the number of estimated parameters also reduces the flexibility of the model and hence increases forecasting error. We propose a method, the parameter Houlihan, that combines traditional machine learning techniques with data assimilation, to select the right set of model parameters to minimize forecasting error while reducing identifiability problems. The method worked well: the data assimilation-based glucose forecasts and estimates for our cohort using the Houlihan-selected parameter sets generally also minimize forecasting errors compared to other parameter selection methods such as by-hand parameter selection. Nevertheless, the forecast with the lowest forecast error does not always accurately represent physiology, but further advancements of the algorithm provide a path for improving physiologic fidelity as well. Our hope is that this methodology represents a first step toward combining machine learning with data assimilation and provides a lower-threshold entry point for using data assimilation with clinical data by helping select the right parameters to estimate

A study of parameter identification

A set of definitions for deterministic parameter identification ability were proposed. Deterministic parameter identificability properties are presented based on four system characteristics: direct parameter recoverability, properties of the system transfer function, properties of output distinguishability, and uniqueness properties of a quadratic cost functional. Stochastic parameter identifiability was defined in terms of the existence of an estimation sequence for the unknown parameters which is consistent in probability. Stochastic parameter identifiability properties are presented based on the following characteristics: convergence properties of the maximum likelihood estimate, properties of the joint probability density functions of the observations, and properties of the information matrix

Asymptotic normality of maximum likelihood and its variational approximation for stochastic blockmodels

Variational methods for parameter estimation are an active research area, potentially offering computationally tractable heuristics with theoretical performance bounds. We build on recent work that applies such methods to network data, and establish asymptotic normality rates for parameter estimates of stochastic blockmodel data, by either maximum likelihood or variational estimation. The result also applies to various sub-models of the stochastic blockmodel found in the literature.Comment: Published in at http://dx.doi.org/10.1214/13-AOS1124 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

The identifiability of tree topology for phylogenetic models, including covarion and mixture models

For a model of molecular evolution to be useful for phylogenetic inference, the topology of evolutionary trees must be identifiable. That is, from a joint distribution the model predicts, it must be possible to recover the tree parameter. We establish tree identifiability for a number of phylogenetic models, including a covarion model and a variety of mixture models with a limited number of classes. The proof is based on the introduction of a more general model, allowing more states at internal nodes of the tree than at leaves, and the study of the algebraic variety formed by the joint distributions to which it gives rise. Tree identifiability is first established for this general model through the use of certain phylogenetic invariants.Comment: 20 pages, 1 figur

Bayesian Updating, Model Class Selection and Robust Stochastic Predictions of Structural Response

A fundamental issue when predicting structural response by using mathematical models is how to treat both modeling and excitation uncertainty. A general framework for this is presented which uses probability as a multi-valued conditional logic for quantitative plausible reasoning in the presence of uncertainty due to incomplete information. The fundamental probability models that represent the structure’s uncertain behavior are specified by the choice of a stochastic system model class: a set of input-output probability models for the structure and a prior probability distribution over this set that quantifies the relative plausibility of each model. A model class can be constructed from a parameterized deterministic structural model by stochastic embedding utilizing Jaynes’ Principle of Maximum Information Entropy. Robust predictive analyses use the entire model class with the probabilistic predictions of each model being weighted by its prior probability, or if structural response data is available, by its posterior probability from Bayes’ Theorem for the model class. Additional robustness to modeling uncertainty comes from combining the robust predictions of each model class in a set of competing candidates weighted by the prior or posterior probability of the model class, the latter being computed from Bayes’ Theorem. This higherlevel application of Bayes’ Theorem automatically applies a quantitative Ockham razor that penalizes the data-fit of more complex model classes that extract more information from the data. Robust predictive analyses involve integrals over highdimensional spaces that usually must be evaluated numerically. Published applications have used Laplace's method of asymptotic approximation or Markov Chain Monte Carlo algorithms