Sparse graphical models for exploring gene expression data

We discuss the theoretical structure and constructive methodology for large-scale graphical models, motivated by their potential in evaluating and aiding the exploration of patterns of association in gene expression data. The theoretical discussion covers basic ideas and connections between Gaussian graphical models, dependency networks and specific classes of directed acyclic graphs we refer to as compositional networks. We describe a constructive approach to generating interesting graphical models for very high-dimensional distributions that builds on the relationships between these various stylized graphical representations. Issues of consistency of models and priors across dimension are key. The resulting methods are of value in evaluating patterns of association in large-scale gene expression data with a view to generating biological insights about genes related to a known molecular pathway or set of specified genes. Some initial examples relate to the estrogen receptor pathway in breast cancer, and the Rb-E2F cell proliferation control pathway.     

Robust weighted orthogonal regression in the errors-in-variables model

This paper focuses on robust estimation in the structural errors-in-variables (EV) model. A new class of robust estimators, called weighted orthogonal regression estimators, is introduced. Robust estimators of the parameters of the EV model are simply derived from robust estimators of multivariate location and scatter such as the M-estimators, the S-estimators and the MCD estimator. The influence functions of the proposed estimators are calculated and shown to be bounded. Moreover, we derive the asymptotic distributions of the estimators and illustrate the results on simulated examples and on a real-data set.     

Bias of the structural quasi-score estimator of a measurement error model under misspecification of the regressor distribution

In a structural measurement error model the structural quasi-score (SQS) estimator is based on the distribution of the latent regressor variable. If this distribution is misspecified, the SQS estimator is (asymptotically) biased. Two types of misspecification are considered. Both assume that the statistician erroneously adopts a normal distribution as his model for the regressor distribution. In the first type of misspecification, the true model consists of a mixture of normal distributions which cluster around a single normal distribution, in the second type, the true distribution is a normal distribution admixed with a second normal distribution of low weight. In both cases of misspecification, the bias, of course, tends to zero when the size of misspecification tends to zero. However, in the first case the bias goes to zero in a flat way so that small deviations from the true model lead to a negligible bias, whereas in the second case the bias is noticeable even for small deviations from the true model.     

Robust parameter estimation with a small bias against heavy contamination

In this paper we consider robust parameter estimation based on a certain cross entropy and divergence. The robust estimate is defined as the minimizer of the empirically estimated cross entropy. It is shown that the robust estimate can be regarded as a kind of projection from the viewpoint of a Pythagorean relation based on the divergence. This property implies that the bias caused by outliers can become sufficiently small even in the case of heavy contamination. It is seen that the asymptotic variance of the robust estimator is naturally overweighted in proportion to the ratio of contamination. One may surmise that another form of cross entropy can present the same behavior as that discussed above. It can be proved under some conditions that no cross entropy can present the same behavior except for the cross entropy considered here and its monotone transformation.     

Robust tests based on dual divergence estimators and saddlepoint approximations

This paper is devoted to robust hypothesis testing based on saddlepoint approximations in the framework of general parametric models. As is known, two main problems can arise when using classical tests. First, the models are approximations of reality and slight deviations from them can lead to unreliable results when using classical tests based on these models. Then, even if a model is correctly chosen, the classical tests are based on first order asymptotic theory. This can lead to inaccurate p-values when the sample size is moderate or small. To overcome these problems, robust tests based on dual divergence estimators and saddlepoint approximations, with good performances in small samples, are proposed.     

Extreme inaccuracies in Gaussian Bayesian networks

To evaluate the impact of model inaccuracies over the network’s output, after the evidence propagation, in a Gaussian Bayesian network, a sensitivity measure is introduced. This sensitivity measure is the Kullback-Leibler divergence and yields different expressions depending on the type of parameter to be perturbed, i.e. on the inaccurate parameter.In this work, the behavior of this sensitivity measure is studied when model inaccuracies are extreme, i.e. when extreme perturbations of the parameters can exist. Moreover, the sensitivity measure is evaluated for extreme situations of dependence between the main variables of the network and its behavior with extreme inaccuracies. This analysis is performed to find the effect of extreme uncertainty about the initial parameters of the model in a Gaussian Bayesian network and about extreme values of evidence. These ideas and procedures are illustrated with an example.     

Robust estimation of periodic autoregressive processes in the presence of additive outliers

This paper suggests a robust estimation procedure for the parameters of the periodic AR (PAR) models when the data contains additive outliers. The proposed robust methodology is an extension of the robust scale and covariance functions given in, respectively, Rousseeuw and Croux (1993) [28], and Ma and Genton (2000) [23] to accommodate periodicity. These periodic robust functions are used in the Yule-Walker equations to obtain robust parameter estimates. The asymptotic central limit theorems of the estimators are established, and an extensive Monte Carlo experiment is conducted to evaluate the performance of the robust methodology for periodic time series with finite sample sizes. The quarterly Fraser River data was used as an example of application of the proposed robust methodology. All the results presented here give strong motivation to use the methodology in practical situations in which periodically correlated time series contain additive outliers.     

Autoregressive process modeling via the Lasso procedure

The Lasso is a popular model selection and estimation procedure for linear models that enjoys nice theoretical properties. In this paper, we study the Lasso estimator for fitting autoregressive time series models. We adopt a double asymptotic framework where the maximal lag may increase with the sample size. We derive theoretical results establishing various types of consistency. In particular, we derive conditions under which the Lasso estimator for the autoregressive coefficients is model selection consistent, estimation consistent and prediction consistent. Simulation study results are reported.     

On the false discovery proportion convergence under Gaussian equi-correlation

We study the convergence of the false discovery proportion (FDP) of the Benjamini-Hochberg procedure in the Gaussian equi-correlated model, when the correlation ρ_m converges to zero as the hypothesis number m grows to infinity. In this model, the FDP converges to the false discovery rate (FDR) at rate {min(m,1/ρ_m)}^1/2, which is different from the standard convergence rate m^1/2 holding under independence.     

On spline regression under Gaussian subordination with long memory

Motivated by an example from neurobiology, we consider estimation in a spline regression model with long-range dependent errors that are generated by Gaussian subordination. Consistency and the asymptotic distribution are derived for general Hermite ranks. Simulations illustrate the asymptotic results and finite sample properties. The method is applied to optical measurements of calcium concentration in the antennal lobe of honey bees used in the study of olfactory patterns.     

Positivity for Gaussian graphical models

Gaussian graphical models are parametric statistical models for jointly normal random variables whose dependence structure is determined by a graph. In previous work, we introduced trek separation, which gives a necessary and sufficient condition in terms of the graph for when a subdeterminant is zero for all covariance matrices that belong to the Gaussian graphical model. Here we extend this result to give explicit cancellation-free formulas for the expansions of non-zero subdeterminants.     

Asymptotic Bayesian structure learning using graph supports for Gaussian graphical models

The theory of Gaussian graphical models is a powerful tool for independence analysis between continuous variables. In this framework, various methods have been conceived to infer independence relations from data samples. However, most of them result in stepwise, deterministic, descent algorithms that are inadequate for solving this issue. More recent developments have focused on stochastic procedures, yet they all base their research on strong a priori knowledge and are unable to perform model selection among the set of all possible models. Moreover, convergence of the corresponding algorithms is slow, precluding applications on a large scale. In this paper, we propose a novel Bayesian strategy to deal with structure learning. Relating graphs to their supports, we convert the problem of model selection into that of parameter estimation. Use of non-informative priors and asymptotic results yield a posterior probability for independence graph supports in closed form. Gibbs sampling is then applied to approximate the full joint posterior density. We finally give three examples of structure learning, one from synthetic data, and the two others from real data.     

A robust estimator of multivariate location based on projection

This paper presents an estimator of location vector based on one-dimensional projection of high dimensional data. The properties of the new estimator including consistency ,asymptotic normality and robustness are discussed. It is proved that the estimator is not only stronglyconsistent and asymptotically normal but also with a breakdown point 1/2 and a bounded influence function.     

Robust regression function estimation

A robust estimator of the regression function is proposed combining kernel methods as introduced for density estimation and robust location estimation techniques. Weak and strong consistency and asymptotic normality are shown under mild conditions on the kernel sequence. The asymptotic variance is a product from a factor depending only on the kernel and a factor similar to the asymptotic variance in robust estimation of location. The estimation is minimax robust in the sense of Huber (1964). Robust estimation of a location parameter. Ann. Math. Statist.33 73–101.     

Robust Bayesian prediction and estimation under a squared log error loss function

Robust Bayesian analysis is concerned with the problem of making decisions about some future observation or an unknown parameter, when the prior distribution belongs to a class Γ instead of being specified exactly. In this paper, the problem of robust Bayesian prediction and estimation under a squared log error loss function is considered. We find the posterior regret Γ-minimax predictor and estimator in a general class of distributions. Furthermore, we construct the conditional Γ-minimax, most stable and least sensitive prediction and estimation in a gamma model. A prequential analysis is carried out by using a simulation study to compare these predictors.     

Robust estimation of Cronbach's alpha

Cronbach's alpha is a popular method to measure reliability, e.g. in quantifying the reliability of a score to summarize the information of several items in questionnaires. The alpha coefficient is known to be non-robust. We study the behavior of this coefficient in different settings to identify situations where Cronbach's alpha is extremely sensitive to violations of the classical model assumptions. Furthermore, we construct a robust version of Cronbach's alpha which is insensitive to a small proportion of data that belong to a different source. The idea is that the robust Cronbach's alpha reflects the reliability of the bulk of the data. For example, it should not be possible that some small amount of outliers makes a score look reliable if it is not.     

Robust estimation in generalized semiparametric mixed models for longitudinal data

In this paper, we consider robust generalized estimating equations for the analysis of semiparametric generalized partial linear mixed models (GPLMMs) for longitudinal data. We approximate the non-parametric function in the GPLMM by a regression spline, and make use of bounded scores and leverage-based weights in the estimating equation to achieve robustness against outliers and influential data points, respectively. Under some regularity conditions, the asymptotic properties of the robust estimators are investigated. To avoid the computational problems involving high-dimensional integrals in our estimators, we adopt a robust Monte Carlo Newton-Raphson (RMCNR) algorithm for fitting GPLMMs. Small simulations are carried out to study the behavior of the robust estimates in the presence of outliers, and these estimates are also compared to their corresponding non-robust estimates. The proposed robust method is illustrated in the analysis of two real data sets.     

Angular Gaussian and Cauchy estimation

This paper proposes a unified treatment of maximum likelihood estimates of angular Gaussian and multivariate Cauchy distributions in both the real and the complex case. The complex case is relevant in shape analysis. We describe in full generality the set of maxima of the corresponding log-likelihood functions with respect to an arbitrary probability measure. Our tools are the convexity of log-likelihood functions and their behaviour at infinity.     

Statistical estimation of a mixture of Gaussian distributions

The paper is devoted to the problem of statistical estimation of a multivariate distribution density, which is a discrete mixture of Gaussian distributions. A heuristic approach is considered, based on the use of the EM algorithm and nonparametric density estimation with a sequential increase in the number of components of the mixture. Criteria for testing of model adequacy are discussed.     

Multivariate generalized S-estimators

In this paper we introduce generalized S-estimators for the multivariate regression model. This class of estimators combines high robustness and high efficiency. They are defined by minimizing the determinant of a robust estimator of the scatter matrix of differences of residuals. In the special case of a multivariate location model, the generalized S-estimator has the important independence property, and can be used for high breakdown estimation in independent component analysis. Robustness properties of the estimators are investigated by deriving their breakdown point and the influence function. We also study the efficiency of the estimators, both asymptotically and at finite samples. To obtain inference for the regression parameters, we discuss the fast and robust bootstrap for multivariate generalized S-estimators. The method is illustrated on a real data example.