Summary
Models of dynamic networks — networks that evolve over time — have manifold applications. We develop a discrete-time generative model for social network evolution that inherits the richness and flexibility of the class of exponential-family random graph models. The model — a Separable Temporal ERGM (STERGM) — facilitates separable modeling of the tie duration distributions and the structural dynamics of tie formation. We develop likelihood-based inference for the model, and provide computational algorithms for maximum likelihood estimation. We illustrate the interpretability of the model in analyzing a longitudinal network of friendship ties within a school.
doi:10.1111/rssb.12014
PMCID: PMC3891677
PMID: 24443639
Social networks; Longitudinal; Exponential random graph model; Markov chain Monte Carlo; Maximum likelihood estimation
Multi-phased designs and biased sampling designs are two of the well recognized approaches to enhance study efficiency. In this paper, we propose a new and cost-effective sampling design, the two-phase probability dependent sampling design (PDS), for studies with a continuous outcome. This design will enable investigators to make efficient use of resources by targeting more informative subjects for sampling. We develop a new semiparametric empirical likelihood inference method to take advantage of data obtained through a PDS design. Simulation study results indicate that the proposed sampling scheme, coupled with the proposed estimator, is more efficient and more powerful than the existing outcome dependent sampling design and the simple random sampling design with the same sample size. We illustrate the proposed method with a real data set from an environmental epidemiologic study.
doi:10.1111/rssb.12029
PMCID: PMC3984585
PMID: 24737947
Empirical likelihood; Missing data; Semiparametric; Probability sample
A sufficient cause interaction between two exposures signals the presence of individuals for whom the outcome would occur only under certain values of the two exposures. When the outcome is dichotomous and all exposures are categorical, then under certain no confounding assumptions, empirical conditions for sufficient cause interactions can be constructed based on the sign of linear contrasts of conditional outcome probabilities between differently exposed subgroups, given confounders. It is argued that logistic regression models are unsatisfactory for evaluating such contrasts, and that Bernoulli regression models with linear link are prone to misspecification. We therefore develop semiparametric tests for sufficient cause interactions under models which postulate probability contrasts in terms of a finite-dimensional parameter, but which are otherwise unspecified. Estimation is often not feasible in these models because it would require nonparametric estimation of auxiliary conditional expectations given high-dimensional variables. We therefore develop ‘multiply robust tests’ under a union model that assumes at least one of several working submodels holds. In the special case of a randomized experiment or a family-based genetic study in which the joint exposure distribution is known by design or Mendelian inheritance, the procedure leads to asymptotically distribution-free tests of the null hypothesis of no sufficient cause interaction.
doi:10.1111/j.1467-9868.2011.01011.x
PMCID: PMC4280915
PMID: 25558182
Double robustness; Effect modification; Gene-environment interaction; Gene-gene interaction; Semiparametric inference; Sufficient cause; Synergism
Summary
We consider rules for discarding predictors in lasso regression and related problems, for computational efficiency. El Ghaoui and his colleagues have propose ‘SAFE’ rules, based on univariate inner products between each predictor and the outcome, which guarantee that a coefficient will be 0 in the solution vector. This provides a reduction in the number of variables that need to be entered into the optimization. We propose strong rules that are very simple and yet screen out far more predictors than the SAFE rules. This great practical improvement comes at a price: the strong rules are not foolproof and can mistakenly discard active predictors, i.e. predictors that have non-zero coefficients in the solution. We therefore combine them with simple checks of the Karush–Kuhn–Tucker conditions to ensure that the exact solution to the convex problem is delivered. Of course, any (approximate) screening method can be combined with the Karush–Kuhn–Tucker, conditions to ensure the exact solution; the strength of the strong rules lies in the fact that, in practice, they discard a very large number of the inactive predictors and almost never commit mistakes. We also derive conditions under which they are foolproof. Strong rules provide substantial savings in computational time for a variety of statistical optimization problems.
doi:10.1111/j.1467-9868.2011.01004.x
PMCID: PMC4262615
PMID: 25506256
Summary
Formal rules governing signed edges on causal directed acyclic graphs are described in this paper and it is shown how these rules can be useful in reasoning about causality. Specifically, the notions of a monotonic effect, a weak monotonic effect and a signed edge are introduced. Results are developed relating these monotonic effects and signed edges to the sign of the causal effect of an intervention in the presence of intermediate variables. The incorporation of signed edges into the directed acyclic graph causal framework furthermore allows for the development of rules governing the relationship between monotonic effects and the sign of the covariance between two variables. It is shown that when certain assumptions about monotonic effects can be made then these results can be used to draw conclusions about the presence of causal effects even when data is missing on confounding variables.
doi:10.1111/j.1467-9868.2009.00728.x
PMCID: PMC4239133
PMID: 25419168
Bias; Causal inference; Confounding; Directed acyclic graphs; Structural equations
Marginal log-linear (MLL) models provide a flexible approach to multivariate discrete data. MLL parametrizations under linear constraints induce a wide variety of models, including models defined by conditional independences. We introduce a subclass of MLL models which correspond to Acyclic Directed Mixed Graphs (ADMGs) under the usual global Markov property. We characterize for precisely which graphs the resulting parametrization is variation independent. The MLL approach provides the first description of ADMG models in terms of a minimal list of constraints. The parametrization is also easily adapted to sparse modelling techniques, which we illustrate using several examples of real data.
doi:10.1111/rssb.12020
PMCID: PMC3754910
PMID: 23997643
acyclic directed mixed graph; discrete graphical model; marginal log-linear parameter; parsimonious modelling; variation independence
Estimation of high-dimensional covariance matrices is known to be a difficult problem, has many applications, and is of current interest to the larger statistics community. In many applications including so-called the “large p small n” setting, the estimate of the covariance matrix is required to be not only invertible, but also well-conditioned. Although many regularization schemes attempt to do this, none of them address the ill-conditioning problem directly. In this paper, we propose a maximum likelihood approach, with the direct goal of obtaining a well-conditioned estimator. No sparsity assumption on either the covariance matrix or its inverse are are imposed, thus making our procedure more widely applicable. We demonstrate that the proposed regularization scheme is computationally efficient, yields a type of Steinian shrinkage estimator, and has a natural Bayesian interpretation. We investigate the theoretical properties of the regularized covariance estimator comprehensively, including its regularization path, and proceed to develop an approach that adaptively determines the level of regularization that is required. Finally, we demonstrate the performance of the regularized estimator in decision-theoretic comparisons and in the financial portfolio optimization setting. The proposed approach has desirable properties, and can serve as a competitive procedure, especially when the sample size is small and when a well-conditioned estimator is required.
doi:10.1111/j.1467-9868.2012.01049.x
PMCID: PMC3667751
PMID: 23730197
covariance estimation; regularization; convex optimization; condition number; eigenvalue; shrinkage; cross-validation; risk comparisons; portfolio optimization
Summary
Modern technologies are producing a wealth of data with complex structures. For instance, in two-dimensional digital imaging, flow cytometry and electroencephalography, matrix-type covariates frequently arise when measurements are obtained for each combination of two underlying variables. To address scientific questions arising from those data, new regression methods that take matrices as covariates are needed, and sparsity or other forms of regularization are crucial owing to the ultrahigh dimensionality and complex structure of the matrix data. The popular lasso and related regularization methods hinge on the sparsity of the true signal in terms of the number of its non-zero coefficients. However, for the matrix data, the true signal is often of, or can be well approximated by, a low rank structure. As such, the sparsity is frequently in the form of low rank of the matrix parameters, which may seriously violate the assumption of the classical lasso. We propose a class of regularized matrix regression methods based on spectral regularization. A highly efficient and scalable estimation algorithm is developed, and a degrees-of-freedom formula is derived to facilitate model selection along the regularization path. Superior performance of the method proposed is demonstrated on both synthetic and real examples.
doi:10.1111/rssb.12031
PMCID: PMC3956002
PMID: 24648830
Electroencephalography; Multi-dimensional array; Nesterov method; Nuclear norm; Spectral regularization; Tensor regression
Summary
This paper develops nonparametric methods based on contact intervals for the analysis of infectious disease data. The contact interval from person i to person j is the time between the onset of infectiousness in i and infectious contact from i to j, where we define infectious contact as a contact sufficient to infect a susceptible individual. The hazard function of the contact interval distribution equals the hazard of infectious contact from i to j, so it provides a summary of the evolution of infectiousness over time. When who-infects-whom is observed, the Nelson-Aalen estimator produces an unbiased estimate of the cumulative hazard function of the contact interval distribution. When who-infects-whom is not observed, we use an EM algorithm to average the Nelson-Aalen estimates from all possible combinations of who-infected-whom consistent with the observed data. This converges to a nonparametric maximum likelihood estimate of the cumulative hazard function that we call the marginal Nelson-Aalen estimate. We study the behavior of these methods in simulations and use them to analyze household surveillance data from the 2009 influenza A(H1N1) pandemic.
doi:10.1111/j.1467-9868.2012.01042.x
PMCID: PMC3681432
PMID: 23772180
Chain-binomial models; Contact intervals; Generation intervals; Infectious disease; Nonparametric methods; Survival analysis
This paper deals with the estimation of a high-dimensional covariance with a conditional sparsity structure and fast-diverging eigenvalues. By assuming sparse error covariance matrix in an approximate factor model, we allow for the presence of some cross-sectional correlation even after taking out common but unobservable factors. We introduce the Principal Orthogonal complEment Thresholding (POET) method to explore such an approximate factor structure with sparsity. The POET estimator includes the sample covariance matrix, the factor-based covariance matrix (Fan, Fan, and Lv, 2008), the thresholding estimator (Bickel and Levina, 2008) and the adaptive thresholding estimator (Cai and Liu, 2011) as specific examples. We provide mathematical insights when the factor analysis is approximately the same as the principal component analysis for high-dimensional data. The rates of convergence of the sparse residual covariance matrix and the conditional sparse covariance matrix are studied under various norms. It is shown that the impact of estimating the unknown factors vanishes as the dimensionality increases. The uniform rates of convergence for the unobserved factors and their factor loadings are derived. The asymptotic results are also verified by extensive simulation studies. Finally, a real data application on portfolio allocation is presented.
doi:10.1111/rssb.12016
PMCID: PMC3859166
PMID: 24348088
High-dimensionality; approximate factor model; unknown factors; principal components; sparse matrix; low-rank matrix; thresholding; cross-sectional correlation; diverging eigenvalues
Summary
Primary analysis of case–control studies focuses on the relationship between disease D and a set of covariates of interest (Y, X). A secondary application of the case–control study, which is often invoked in modern genetic epidemiologic association studies, is to investigate the interrelationship between the covariates themselves. The task is complicated owing to the case–control sampling, where the regression of Y on X is different from what it is in the population. Previous work has assumed a parametric distribution for Y given X and derived semiparametric efficient estimation and inference without any distributional assumptions about X. We take up the issue of estimation of a regression function when Y given X follows a homoscedastic regression model, but otherwise the distribution of Y is unspecified. The semiparametric efficient approaches can be used to construct semiparametric efficient estimates, but they suffer from a lack of robustness to the assumed model for Y given X. We take an entirely different approach. We show how to estimate the regression parameters consistently even if the assumed model for Y given X is incorrect, and thus the estimates are model robust. For this we make the assumption that the disease rate is known or well estimated. The assumption can be dropped when the disease is rare, which is typically so for most case–control studies, and the estimation algorithm simplifies. Simulations and empirical examples are used to illustrate the approach.
doi:10.1111/j.1467-9868.2012.01052.x
PMCID: PMC3639015
PMID: 23637568
Biased samples; Homoscedastic regression; Secondary data; Secondary phenotypes; Semiparametric inference; Two-stage samples
This paper develops a new estimation of nonparametric regression functions for clustered or longitudinal data. We propose to use Cholesky decomposition and profile least squares techniques to estimate the correlation structure and regression function simultaneously. We further prove that the proposed estimator is as asymptotically efficient as if the covariance matrix were known. A Monte Carlo simulation study is conducted to examine the finite sample performance of the proposed procedure, and to compare the proposed procedure with the existing ones. Based on our empirical studies, the newly proposed procedure works better than the naive local linear regression with working independence error structure and the efficiency gain can be achieved in moderate-sized samples. Our numerical comparison also shows that the newly proposed procedure outperforms some existing ones. A real data set application is also provided to illustrate the proposed estimation procedure.
doi:10.1111/j.1467-9868.2012.01038.x
PMCID: PMC3607647
PMID: 23539417
Cholesky decomposition; Local polynomial regression; Longitudinal data; Profile least squares
In this article, a stepwise procedure, correlation pursuit (COP), is developed for variable selection under the sufficient dimension reduction framework, in which the response variable Y is influenced by the predictors X1, X2, …, Xp through an unknown function of a few linear combinations of them. Unlike linear stepwise regression, COP does not impose a special form of relationship (such as linear) between the response variable and the predictor variables. The COP procedure selects variables that attain the maximum correlation between the transformed response and the linear combination of the variables. Various asymptotic properties of the COP procedure are established, and in particular, its variable selection performance under diverging number of predictors and sample size has been investigated. The excellent empirical performance of the COP procedure in comparison with existing methods are demonstrated by both extensive simulation studies and a real example in functional genomics.
doi:10.1111/j.1467-9868.2011.01026.x
PMCID: PMC3519449
PMID: 23243388
variable selection; projection pursuit regression; sliced inverse regression; stepwise regression; dimension reduction
Summary
Copy number variants (CNVs) are alternations of DNA of a genome that results in the cell having a less or more than two copies of segments of the DNA. CNVs correspond to relatively large regions of the genome, ranging from about one kilobase to several megabases, that are deleted or duplicated. Motivated by CNV analysis based on next generation sequencing data, we consider the problem of detecting and identifying sparse short segments hidden in a long linear sequence of data with an unspecified noise distribution. We propose a computationally efficient method that provides a robust and near-optimal solution for segment identification over a wide range of noise distributions. We theoretically quantify the conditions for detecting the segment signals and show that the method near-optimally estimates the signal segments whenever it is possible to detect their existence. Simulation studies are carried out to demonstrate the efficiency of the method under different noise distributions. We present results from a CNV analysis of a HapMap Yoruban sample to further illustrate the theory and the methods.
doi:10.1111/j.1467-9868.2012.01028.x
PMCID: PMC3563068
PMID: 23393425
Robust segment detector; Robust segment identifier; optimality; DNA copy number variant; next generation sequencing data
Summary
Local polynomial regression has received extensive attention for the nonparametric estimation of regression functions when both the response and the covariate are in Euclidean space. However, little has been done when the response is in a Riemannian manifold. We develop an intrinsic local polynomial regression estimate for the analysis of symmetric positive definite (SPD) matrices as responses that lie in a Riemannian manifold with covariate in Euclidean space. The primary motivation and application of the proposed methodology is in computer vision and medical imaging. We examine two commonly used metrics, including the trace metric and the Log-Euclidean metric on the space of SPD matrices. For each metric, we develop a cross-validation bandwidth selection method, derive the asymptotic bias, variance, and normality of the intrinsic local constant and local linear estimators, and compare their asymptotic mean square errors. Simulation studies are further used to compare the estimators under the two metrics and to examine their finite sample performance. We use our method to detect diagnostic differences between diffusion tensors along fiber tracts in a study of human immunodeficiency virus.
doi:10.1111/j.1467-9868.2011.01022.x
PMCID: PMC3448376
PMID: 23008683
Summary
For high-dimensional classification, it is well known that naively performing the Fisher discriminant rule leads to poor results due to diverging spectra and noise accumulation. Therefore, researchers proposed independence rules to circumvent the diverging spectra, and sparse independence rules to mitigate the issue of noise accumulation. However, in biological applications, there are often a group of correlated genes responsible for clinical outcomes, and the use of the covariance information can significantly reduce misclassification rates. In theory the extent of such error rate reductions is unveiled by comparing the misclassification rates of the Fisher discriminant rule and the independence rule. To materialize the gain based on finite samples, a Regularized Optimal Affine Discriminant (ROAD) is proposed. ROAD selects an increasing number of features as the regularization relaxes. Further benefits can be achieved when a screening method is employed to narrow the feature pool before hitting the ROAD. An efficient Constrained Coordinate Descent algorithm (CCD) is also developed to solve the associated optimization problems. Sampling properties of oracle type are established. Simulation studies and real data analysis support our theoretical results and demonstrate the advantages of the new classification procedure under a variety of correlation structures. A delicate result on continuous piecewise linear solution path for the ROAD optimization problem at the population level justifies the linear interpolation of the CCD algorithm.
PMCID: PMC3467977
PMID: 23074363
High Dimensional Classification; LDA; Regularized Optimal Affine Discriminant; Fisher Discriminant; Independence Rule
Summary
We study the heteroscedastic partially linear single-index model with an unspecified error variance function, which allows for high dimensional covariates in both the linear and the single-index components of the mean function. We propose a class of consistent estimators of the parameters by using a proper weighting strategy. An interesting finding is that the linearity condition which is widely assumed in the dimension reduction literature is not necessary for methodological or theoretical development: it contributes only to the simplification of non-optimal consistent estimation. We also find that the performance of the usual weighted least square type of estimators deteriorates when the non-parametric component is badly estimated. However, estimators in our family automatically provide protection against such deterioration, in that the consistency can be achieved even if the baseline non-parametric function is completely misspecified. We further show that the most efficient estimator is a member of this family and can be easily obtained by using non-parametric estimation. Properties of the estimators proposed are presented through theoretical illustration and numerical simulations. An example on gender discrimination is used to demonstrate and to compare the practical performance of the estimators.
doi:10.1111/j.1467-9868.2012.01040.x
PMCID: PMC3747813
PMID: 23970823
Dimension reduction; Double robustness; Linearity condition; Semiparametric efficiency bound; Single index model
Summary
It is now common to survey microbial communities by sequencing nucleic acid material extracted in bulk from a given environment. Comparative methods are needed that indicate the extent to which two communities differ given data sets of this type. UniFrac, which gives a somewhat ad hoc phylogenetics-based distance between two communities, is one of the most commonly used tools for these analyses. We provide a foundation for such methods by establishing that, if we equate a metagenomic sample with its empirical distribution on a reference phylogenetic tree, then the weighted UniFrac distance between two samples is just the classical Kantorovich–Rubinstein, or earth mover’s, distance between the corresponding empirical distributions. We demonstrate that this Kantorovich–Rubinstein distance and extensions incorporating uncertainty in the sample locations can be written as a readily computable integral over the tree, we develop Lp Zolotarev-type generalizations of the metric, and we show how the p-value of the resulting natural permutation test of the null hypothesis ‘no difference between two communities’ can be approximated by using a Gaussian process functional. We relate the L2-case to an analysis-of-variance type of decomposition, finding that the distribution of its associated Gaussian functional is that of a computable linear combination of independent
χ12 random variables.
doi:10.1111/j.1467-9868.2011.01018.x
PMCID: PMC3405733
PMID: 22844205
Barycentre; CAT(κ)space; Gaussian process; Hadamard space; Metagenomics; Monte Carlo methods; Negative curvature; Optimal transport; Permutation test; Phylogenetics; Randomization test; Reproducing kernel Hilbert space; Wasserstein metric
Summary
Association models, like frailty and copula models, are frequently used to analyze clustered survival data and evaluate within-cluster associations. The assumption of noninformative censoring is commonly applied to these models, though it may not be true in many situations. In this paper, we consider bivariate competing risk data and focus on association models specified for the bivariate cumulative incidence function (CIF), a nonparametrically identifiable quantity. Copula models are proposed which relate the bivariate CIF to its corresponding univariate CIFs, similarly to independently right censored data, and accommodate frailty models for the bivariate CIF. Two estimating equations are developed to estimate the association parameter, permitting the univariate CIFs to be estimated either parametrically or nonparametrically. Goodness-of-fit tests are presented for formally evaluating the parametric models. Both estimators perform well with moderate sample sizes in simulation studies. The practical use of the methodology is illustrated in an analysis of dementia associations.
doi:10.1111/j.1467-9868.2011.01012.x
PMCID: PMC3322730
PMID: 22505835
Summary
Variance estimation is a fundamental problem in statistical modelling. In ultrahigh dimensional linear regression where the dimensionality is much larger than the sample size, traditional variance estimation techniques are not applicable. Recent advances in variable selection in ultrahigh dimensional linear regression make this problem accessible. One of the major problems in ultrahigh dimensional regression is the high spurious correlation between the unobserved realized noise and some of the predictors. As a result, the realized noises are actually predicted when extra irrelevant variables are selected, leading to serious underestimate of the level of noise. We propose a two-stage refitted procedure via a data splitting technique, called refitted cross-validation, to attenuate the influence of irrelevant variables with high spurious correlations. Our asymptotic results show that the resulting procedure performs as well as the oracle estimator, which knows in advance the mean regression function. The simulation studies lend further support to our theoretical claims. The naive two-stage estimator and the plug-in one-stage estimators using the lasso and smoothly clipped absolute deviation are also studied and compared. Their performances can be improved by the reffitted cross-validation method proposed.
doi:10.1111/j.1467-9868.2011.01005.x
PMCID: PMC3271712
PMID: 22312234
Data splitting; Dimension reduction; High dimensionality; Refitted cross-validation; Sure screening; Variance estimation; Variable selection
Summary
We consider the supervised classification setting, in which the data consist of p features measured on n observations, each of which belongs to one of K classes. Linear discriminant analysis (LDA) is a classical method for this problem. However, in the high-dimensional setting where p ≫ n, LDA is not appropriate for two reasons. First, the standard estimate for the within-class covariance matrix is singular, and so the usual discriminant rule cannot be applied. Second, when p is large, it is difficult to interpret the classification rule obtained from LDA, since it involves all p features. We propose penalized LDA, a general approach for penalizing the discriminant vectors in Fisher’s discriminant problem in a way that leads to greater interpretability. The discriminant problem is not convex, so we use a minorization-maximization approach in order to efficiently optimize it when convex penalties are applied to the discriminant vectors. In particular, we consider the use of L1 and fused lasso penalties. Our proposal is equivalent to recasting Fisher’s discriminant problem as a biconvex problem. We evaluate the performances of the resulting methods on a simulation study, and on three gene expression data sets. We also survey past methods for extending LDA to the high-dimensional setting, and explore their relationships with our proposal.
doi:10.1111/j.1467-9868.2011.00783.x
PMCID: PMC3272679
PMID: 22323898
classification; feature selection; high dimensional; lasso; linear discriminant analysis; supervised learning
In many situations information from a sample of individuals can be supplemented by population level information on the relationship between a dependent variable and explanatory variables. Inclusion of the population level information can reduce bias and increase the efficiency of the parameter estimates.
Population level information can be incorporated via constraints on functions of the model parameters. In general the constraints are nonlinear making the task of maximum likelihood estimation harder. In this paper we develop an alternative approach exploiting the notion of an empirical likelihood. It is shown that within the framework of generalised linear models, the population level information corresponds to linear constraints, which are comparatively easy to handle. We provide a two-step algorithm that produces parameter estimates using only unconstrained estimation. We also provide computable expressions for the standard errors. We give an application to demographic hazard modelling by combining panel survey data with birth registration data to estimate annual birth probabilities by parity.
doi:10.1111/j.1467-9868.2007.00637.x
PMCID: PMC3381521
PMID: 22740776
Empirical Likelihood; Constrained Optimisation; Generalised Linear Models
Summary
In high-dimensional model selection problems, penalized least-square approaches have been extensively used. This paper addresses the question of both robustness and efficiency of penalized model selection methods, and proposes a data-driven weighted linear combination of convex loss functions, together with weighted L1-penalty. It is completely data-adaptive and does not require prior knowledge of the error distribution. The weighted L1-penalty is used both to ensure the convexity of the penalty term and to ameliorate the bias caused by the L1-penalty. In the setting with dimensionality much larger than the sample size, we establish a strong oracle property of the proposed method that possesses both the model selection consistency and estimation efficiency for the true non-zero coefficients. As specific examples, we introduce a robust method of composite L1-L2, and optimal composite quantile method and evaluate their performance in both simulated and real data examples.
doi:10.1111/j.1467-9868.2010.00764.x
PMCID: PMC3094588
PMID: 21589849
Composite QMLE; LASSO; Model Selection; NP Dimensionality; Oracle Property; Robust statistics; SCAD
We consider the problem of optimal design of experiments for random effects models, especially population models, where a small number of correlated observations can be taken on each individual, while the observations corresponding to different individuals are assumed to be uncorrelated. We focus on c-optimal design problems and show that the classical equivalence theorem and the famous geometric characterization of Elfving (1952) from the case of uncorrelated data can be adapted to the problem of selecting optimal sets of observations for the n individual patients. The theory is demonstrated by finding optimal designs for a linear model with correlated observations and a nonlinear random effects population model, which is commonly used in pharmacokinetics.
doi:10.1111/j.1467-9868.2010.00757.x
PMCID: PMC3106301
PMID: 21643483
c-optimal design; correlated observations; Elfving's theorem; pharmacokinetic models; random effects; locally optimal design; geometric characterization
Summary
Neuroimaging studies aim to analyze imaging data with complex spatial patterns in a large number of locations (called voxels) on a two-dimensional (2D) surface or in a 3D volume. Conventional analyses of imaging data include two sequential steps: spatially smoothing imaging data and then independently fitting a statistical model at each voxel. However, conventional analyses suffer from the same amount of smoothing throughout the whole image, the arbitrary choice of smoothing extent, and low statistical power in detecting spatial patterns. We propose a multiscale adaptive regression model (MARM) to integrate the propagation–separation (PS) approach (Polzehl and Spokoiny, 2000, 2006) with statistical modeling at each voxel for spatial and adaptive analysis of neuroimaging data from multiple subjects. MARM has three features: being spatial, being hierarchical, and being adaptive. We use a multiscale adaptive estimation and testing procedure (MAET) to utilize imaging observations from the neighboring voxels of the current voxel to adaptively calculate parameter estimates and test statistics. Theoretically, we establish consistency and asymptotic normality of the adaptive parameter estimates and the asymptotic distribution of the adaptive test statistics. Our simulation studies and real data analysis confirm that MARM significantly outperforms conventional analyses of imaging data.
doi:10.1111/j.1467-9868.2010.00767.x
PMCID: PMC3158617
PMID: 21860598
Kernel; Multiscale adaptive regression; Neuroimaging data; Propagation separation; Smoothing; Sphere; Test statistics