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1.  Automatic Model Selection for Partially Linear Models 
Journal of multivariate analysis  2009;100(9):2100-2111.
We propose and study a unified procedure for variable selection in partially linear models. A new type of double-penalized least squares is formulated, using the smoothing spline to estimate the nonparametric part and applying a shrinkage penalty on parametric components to achieve model parsimony. Theoretically we show that, with proper choices of the smoothing and regularization parameters, the proposed procedure can be as efficient as the oracle estimator (Fan and Li, 2001). We also study the asymptotic properties of the estimator when the number of parametric effects diverges with the sample size. Frequentist and Bayesian estimates of the covariance and confidence intervals are derived for the estimators. One great advantage of this procedure is its linear mixed model (LMM) representation, which greatly facilitates its implementation by using standard statistical software. Furthermore, the LMM framework enables one to treat the smoothing parameter as a variance component and hence conveniently estimate it together with other regression coefficients. Extensive numerical studies are conducted to demonstrate the effective performance of the proposed procedure.
doi:10.1016/j.jmva.2009.06.009
PMCID: PMC2766091  PMID: 20160947
Key words and phrases: Semiparametric regression; Smoothing splines; Smoothly clipped absolute deviation; Variable selection
2.  Analysis of Longitudinal Data with Semiparametric Estimation of Covariance Function 
Improving efficiency for regression coefficients and predicting trajectories of individuals are two important aspects in analysis of longitudinal data. Both involve estimation of the covariance function. Yet, challenges arise in estimating the covariance function of longitudinal data collected at irregular time points. A class of semiparametric models for the covariance function is proposed by imposing a parametric correlation structure while allowing a nonparametric variance function. A kernel estimator is developed for the estimation of the nonparametric variance function. Two methods, a quasi-likelihood approach and a minimum generalized variance method, are proposed for estimating parameters in the correlation structure. We introduce a semiparametric varying coefficient partially linear model for longitudinal data and propose an estimation procedure for model coefficients by using a profile weighted least squares approach. Sampling properties of the proposed estimation procedures are studied and asymptotic normality of the resulting estimators is established. Finite sample performance of the proposed procedures is assessed by Monte Carlo simulation studies. The proposed methodology is illustrated by an analysis of a real data example.
doi:10.1198/016214507000000095
PMCID: PMC2730591  PMID: 19707537
Kernel regression; local linear regression; profile weighted least squares; semiparametric varying coefficient model
3.  GENERALIZED LEAST SQUARES ESTIMATION OF THE MEAN FUNCTION OF A COUNTING PROCESS BASED ON PANEL COUNTS 
Statistica Sinica  2009;19:561-580.
This paper considers nonparametric estimation of the mean function of a counting process based on periodic observations, i.e., panel counts. We present estimators derived through minimizing a class of generalized sums of squares subject to a monotonicity constraint. We establish consistency of the estimators and provide procedures to implement them with various weight functions. For specific weight functions, they reduce to the estimator given in Sun and Kalbfleisch (1995), and are closely related to the nonparametric maximum likelihood estimator studied in Wellner and Zhang (2000). With other weight functions, the proposed estimators provide alternatives that can have better efficiency in non-Poisson situations than previous approaches. Simulations are used to examine the finite-sample performance of the proposed estimators.
PMCID: PMC2835534  PMID: 20221323
Isotonic regression; monotonicity constraint; periodic observations
4.  Semiparametric Frailty Models for Clustered Failure Time Data 
Biometrics  2011;68(2):429-436.
Summary
We consider frailty models with additive semiparametric covariate effects for clustered failure time data. We propose a doubly penalized partial likelihood (DPPL) procedure to estimate the nonparametric functions using smoothing splines. We show that the DPPL estimators could be obtained from fitting an augmented working frailty model with parametric covariate effects, whereas the nonparametric functions being estimated as linear combinations of fixed and random effects, and the smoothing parameters being estimated as extra variance components. This approach allows us to conveniently estimate all model components within a unified frailty model framework. We evaluate the finite sample performance of the proposed method via a simulation study, and apply the method to analyze data from a study of sexually transmitted infections (STI).
doi:10.1111/j.1541-0420.2011.01683.x
PMCID: PMC3600835  PMID: 22070739
Doubly penalized partial likelihood; smoothing spline; Gaussian frailty; sexually transmitted disease; Smoothing parameter; Variance components
5.  Marginal analysis of panel counts through estimating functions 
Biometrika  2009;96(2):445-456.
Summary
We develop nonparametric estimation procedures for the marginal mean function of a counting process based on periodic observations, using two types of self-consistent estimating equations. The first is derived from the likelihood studied in Wellner & Zhang (2000), assuming a Poisson counting process, and gives a nondecreasing estimator, which is the same as the nonparametric maximum likelihood estimator of Wellner & Zhang and thus is consistent without the Poisson assumption. Motivated by the construction of parametric generalized estimating equations, the second type is a set of data-adaptive quasi-score functions, which are likelihood estimating functions under a mixed-Poisson assumption. We evaluate the procedures via simulation, and illustrate them with the data from a bladder cancer study.
doi:10.1093/biomet/asp010
PMCID: PMC2698463  PMID: 19543426
Counting process; Interval censoring; Marginal mean function; Nonparametric estimation; Quasi-score function
6.  Maximum penalized likelihood estimation in a gamma-frailty model 
Lifetime Data Analysis  2003;9(2):139-153.
The shared frailty models allow for unobserved heterogeneity or for statistical dependence between observed survival data. The most commonly used estimation procedure in frailty models is the EM algorithm, but this approach yields a discrete estimator of the distribution and consequently does not allow direct estimation of the hazard function. We show how maximum penalized likelihood estimation can be applied to nonparametric estimation of a continuous hazard function in a shared gamma-frailty model with right-censored and left-truncated data. We examine the problem of obtaining variance estimators for regression coefficients, the frailty parameter and baseline hazard functions. Some simulations for the proposed estimation procedure are presented. A prospective cohort (Paquid) with grouped survival data serves to illustrate the method which was used to analyze the relationship between environmental factors and the risk of dementia.
PMCID: PMC1961627  PMID: 12735493
Frailty models; Correlated survival times; Penalized likelihood; dementia; Aluminum; Algorithms; Aluminum; adverse effects; Alzheimer Disease; chemically induced; epidemiology; Cohort Studies; Environmental Exposure; adverse effects; France; Humans; Likelihood Functions; Proportional Hazards Models; Survival Analysis
7.  Nonparametric Bayesian density estimation on manifolds with applications to planar shapes 
Biometrika  2010;97(4):851-865.
Summary
Statistical analysis on landmark-based shape spaces has diverse applications in morphometrics, medical diagnostics, machine vision and other areas. These shape spaces are non-Euclidean quotient manifolds. To conduct nonparametric inferences, one may define notions of centre and spread on this manifold and work with their estimates. However, it is useful to consider full likelihood-based methods, which allow nonparametric estimation of the probability density. This article proposes a broad class of mixture models constructed using suitable kernels on a general compact metric space and then on the planar shape space in particular. Following a Bayesian approach with a nonparametric prior on the mixing distribution, conditions are obtained under which the Kullback–Leibler property holds, implying large support and weak posterior consistency. Gibbs sampling methods are developed for posterior computation, and the methods are applied to problems in density estimation and classification with shape-based predictors. Simulation studies show improved estimation performance relative to existing approaches.
doi:10.1093/biomet/asq044
PMCID: PMC3371720  PMID: 22822255
Dirichlet process mixture; Discriminant analysis; Kullback–Leibler property; Metric space; Nonparametric Bayes; Planar shape space; Posterior consistency; Riemannian manifold
8.  Correcting for bias in estimation of quantitative trait loci effects 
Estimates of quantitative trait loci (QTL) effects derived from complete genome scans are biased, if no assumptions are made about the distribution of QTL effects. Bias should be reduced if estimates are derived by maximum likelihood, with the QTL effects sampled from a known distribution. The parameters of the distributions of QTL effects for nine economic traits in dairy cattle were estimated from a daughter design analysis of the Israeli Holstein population including 490 marker-by-sire contrasts. A separate gamma distribution was derived for each trait. Estimates for both the α and β parameters and their SE decreased as a function of heritability. The maximum likelihood estimates derived for the individual QTL effects using the gamma distributions for each trait were regressed relative to the least squares estimates, but the regression factor decreased as a function of the least squares estimate. On simulated data, the mean of least squares estimates for effects with nominal 1% significance was more than twice the simulated values, while the mean of the maximum likelihood estimates was slightly lower than the mean of the simulated values. The coefficient of determination for the maximum likelihood estimates was five-fold the corresponding value for the least squares estimates.
doi:10.1186/1297-9686-37-6-501
PMCID: PMC2697222  PMID: 16093012
genetic markers; quantitative trait loci; genome scans; maximum likelihood; dairy cattle
9.  Semiparametric Maximum Likelihood Estimation in Normal Transformation Models for Bivariate Survival Data 
Biometrika  2008;95(4):947-960.
SUMMARY
We consider a class of semiparametric normal transformation models for right censored bivariate failure times. Nonparametric hazard rate models are transformed to a standard normal model and a joint normal distribution is assumed for the bivariate vector of transformed variates. A semiparametric maximum likelihood estimation procedure is developed for estimating the marginal survival distribution and the pairwise correlation parameters. This produces an efficient estimator of the correlation parameter of the semiparametric normal transformation model, which characterizes the bivariate dependence of bivariate survival outcomes. In addition, a simple positive-mass-redistribution algorithm can be used to implement the estimation procedures. Since the likelihood function involves infinite-dimensional parameters, the empirical process theory is utilized to study the asymptotic properties of the proposed estimators, which are shown to be consistent, asymptotically normal and semiparametric efficient. A simple estimator for the variance of the estimates is also derived. The finite sample performance is evaluated via extensive simulations.
doi:10.1093/biomet/asn049
PMCID: PMC2600666  PMID: 19079778
Asymptotic normality; Bivariate failure time; Consistency; Semiparametric efficiency; Semiparametric maximum likelihood estimate; Semiparametric normal transformation
10.  Bias correction for the proportional odds logistic regression model with application to a study of surgical complications 
Summary
The proportional odds logistic regression model is widely used for relating an ordinal outcome to a set of covariates. When the number of outcome categories is relatively large, the sample size is relatively small, and/or certain outcome categories are rare, maximum likelihood can yield biased estimates of the regression parameters. Firth (1993) and Kosmidis and Firth (2009) proposed a procedure to remove the leading term in the asymptotic bias of the maximum likelihood estimator. Their approach is most easily implemented for univariate outcomes. In this paper, we derive a bias correction that exploits the proportionality between Poisson and multinomial likelihoods for multinomial regression models. Specifically, we describe a bias correction for the proportional odds logistic regression model, based on the likelihood from a collection of independent Poisson random variables whose means are constrained to sum to 1, that is straightforward to implement. The proposed method is motivated by a study of predictors of post-operative complications in patients undergoing colon or rectal surgery (Gawande et al., 2007).
PMCID: PMC3729470  PMID: 23913986
Discrete response; multinomial likelihood; multinomial logistic regression; penalized likelihood; Poisson likelihood
11.  Tuning parameter selectors for the smoothly clipped absolute deviation method 
Biometrika  2007;94(3):553-568.
Summary
The penalised least squares approach with smoothly clipped absolute deviation penalty has been consistently demonstrated to be an attractive regression shrinkage and selection method. It not only automatically and consistently selects the important variables, but also produces estimators which are as efficient as the oracle estimator. However, these attractive features depend on appropriately choosing the tuning parameter. We show that the commonly used the generalised crossvalidation cannot select the tuning parameter satisfactorily, with a nonignorable overfitting effect in the resulting model. In addition, we propose a bic tuning parameter selector, which is shown to be able to identify the true model consistently. Simulation studies are presented to support theoretical findings, and an empirical example is given to illustrate its use in the Female Labor Supply data.
doi:10.1093/biomet/asm053
PMCID: PMC2663963  PMID: 19343105
aic; bic; Generalised crossvalidation; Least absolute shrinkage and selection operator; Smoothly clipped absolute deviation
12.  Semiparametric Transformation Models with Random Effects for Joint Analysis of Recurrent and Terminal Events 
Biometrics  2008;65(3):746-752.
Summary
We propose a broad class of semiparametric transformation models with random effects for the joint analysis of recurrent events and a terminal event. The transformation models include proportional hazards/intensity and proportional odds models. We estimate the model parameters by the nonparametric maximum likelihood approach. The estimators are shown to be consistent, asymptotically normal, and asymptotically efficient. Simple and stable numerical algorithms are provided to calculate the parameter estimators and to estimate their variances. Extensive simulation studies demonstrate that the proposed inference procedures perform well in realistic settings. Applications to two HIV/AIDS studies are presented.
doi:10.1111/j.1541-0420.2008.01126.x
PMCID: PMC3030128  PMID: 18945267
Censoring; EM algorithm; Informative dropout; Joint models; Nonparametric maximum likelihood; Proportional hazards; Proportional odds; Random effects; Recurrent events; Shared frailty
13.  Analysing panel count data with informative observation times 
Biometrika  2006;93(4):763-775.
Summary
In this paper, we study panel count data with informative observation times. We assume nonparametric and semiparametric proportional rate models for the underlying event process, where the form of the baseline rate function is left unspecified and a subject-specific frailty variable inflates or deflates the rate function multiplicatively. The proposed models allow the event processes and observation times to be correlated through their connections with the unobserved frailty; moreover, the distributions of both the frailty variable and observation times are considered as nuisance parameters. The baseline rate function and the regression parameters are estimated by maximising a conditional likelihood function of observed event counts and solving estimation equations. Large-sample properties of the proposed estimators are studied. Numerical studies demonstrate that the proposed estimation procedures perform well for moderate sample sizes. An application to a bladder tumour study is presented.
doi:10.1093/biomet/93.4.763
PMCID: PMC3666563  PMID: 23729818
Dependent censoring; Frailty; Poisson process; Rate function; Serial events
14.  A review of statistical estimators for risk-adjusted length of stay: analysis of the Australian and new Zealand intensive care adult patient data-base, 2008–2009 
Background
For the analysis of length-of-stay (LOS) data, which is characteristically right-skewed, a number of statistical estimators have been proposed as alternatives to the traditional ordinary least squares (OLS) regression with log dependent variable.
Methods
Using a cohort of patients identified in the Australian and New Zealand Intensive Care Society Adult Patient Database, 2008–2009, 12 different methods were used for estimation of intensive care (ICU) length of stay. These encompassed risk-adjusted regression analysis of firstly: log LOS using OLS, linear mixed model [LMM], treatment effects, skew-normal and skew-t models; and secondly: unmodified (raw) LOS via OLS, generalised linear models [GLMs] with log-link and 4 different distributions [Poisson, gamma, negative binomial and inverse-Gaussian], extended estimating equations [EEE] and a finite mixture model including a gamma distribution. A fixed covariate list and ICU-site clustering with robust variance were utilised for model fitting with split-sample determination (80%) and validation (20%) data sets, and model simulation was undertaken to establish over-fitting (Copas test). Indices of model specification using Bayesian information criterion [BIC: lower values preferred] and residual analysis as well as predictive performance (R2, concordance correlation coefficient (CCC), mean absolute error [MAE]) were established for each estimator.
Results
The data-set consisted of 111663 patients from 131 ICUs; with mean(SD) age 60.6(18.8) years, 43.0% were female, 40.7% were mechanically ventilated and ICU mortality was 7.8%. ICU length-of-stay was 3.4(5.1) (median 1.8, range (0.17-60)) days and demonstrated marked kurtosis and right skew (29.4 and 4.4 respectively). BIC showed considerable spread, from a maximum of 509801 (OLS-raw scale) to a minimum of 210286 (LMM). R2 ranged from 0.22 (LMM) to 0.17 and the CCC from 0.334 (LMM) to 0.149, with MAE 2.2-2.4. Superior residual behaviour was established for the log-scale estimators. There was a general tendency for over-prediction (negative residuals) and for over-fitting, the exception being the GLM negative binomial estimator. The mean-variance function was best approximated by a quadratic function, consistent with log-scale estimation; the link function was estimated (EEE) as 0.152(0.019, 0.285), consistent with a fractional-root function.
Conclusions
For ICU length of stay, log-scale estimation, in particular the LMM, appeared to be the most consistently performing estimator(s). Neither the GLM variants nor the skew-regression estimators dominated.
doi:10.1186/1471-2288-12-68
PMCID: PMC3522544  PMID: 22591115
15.  Fixed and Random Effects Selection in Mixed Effects Models 
Biometrics  2010;67(2):495-503.
SUMMARY
We consider selecting both fixed and random effects in a general class of mixed effects models using maximum penalized likelihood (MPL) estimation along with the smoothly clipped absolute deviation (SCAD) and adaptive LASSO (ALASSO) penalty functions. The maximum penalized likelihood estimates are shown to posses consistency and sparsity properties and asymptotic normality. A model selection criterion, called the ICQ statistic, is proposed for selecting the penalty parameters (Ibrahim, Zhu and Tang, 2008). The variable selection procedure based on ICQ is shown to consistently select important fixed and random effects. The methodology is very general and can be applied to numerous situations involving random effects, including generalized linear mixed models. Simulation studies and a real data set from an Yale infant growth study are used to illustrate the proposed methodology.
doi:10.1111/j.1541-0420.2010.01463.x
PMCID: PMC3041932  PMID: 20662831
ALASSO; Cholesky decomposition; EM algorithm; ICQ criterion; Mixed Effects selection; Penalized likelihood; SCAD
16.  Covariate-Adjusted Linear Mixed Effects Model with an Application to Longitudinal Data 
Linear mixed effects (LME) models are useful for longitudinal data/repeated measurements. We propose a new class of covariate-adjusted LME models for longitudinal data that nonparametrically adjusts for a normalizing covariate. The proposed approach involves fitting a parametric LME model to the data after adjusting for the nonparametric effects of a baseline confounding covariate. In particular, the effect of the observable covariate on the response and predictors of the LME model is modeled nonparametrically via smooth unknown functions. In addition to covariate-adjusted estimation of fixed/population parameters and random effects, an estimation procedure for the variance components is also developed. Numerical properties of the proposed estimators are investigated with simulation studies. The consistency and convergence rates of the proposed estimators are also established. An application to a longitudinal data set on calcium absorption, accounting for baseline distortion from body mass index, illustrates the proposed methodology.
doi:10.1080/10485250802226435
PMCID: PMC2650843  PMID: 19266053
Binning; Covariance structure; Covariate-adjusted regression (CAR); Longitudinal data; Mixed model; Multiplicative effect; Varying coefficient models
17.  EFFICIENT ESTIMATION FOR AN ACCELERATED FAILURE TIME MODEL WITH A CURE FRACTION 
Statistica Sinica  2010;20:661-674.
We study the accelerated failure time model with a cure fraction via kernel-based nonparametric maximum likelihood estimation. An EM algorithm is developed to calculate the estimates for both the regression parameters and the unknown error density, in which a kernel-smoothed conditional profile likelihood is maximized in the M-step. We show that with a proper choice of the kernel bandwidth parameter, the resulting estimates are consistent and asymptotically normal. The asymptotic covariance matrix can be consistently estimated by inverting the empirical Fisher information matrix obtained from the profile likelihood using the EM algorithm. Numerical examples are used to illustrate the finite-sample performance of the proposed estimates.
PMCID: PMC2857521  PMID: 20414460
Cure model; EM algorithm; kernel smoothing; profile likelihood; survival data
18.  Empirical-likelihood-based semiparametric inference for the treatment effect in the two-sample problem with censoring 
Biometrika  2005;92(2):271-282.
Summary
To compare two samples of censored data, we propose a unified semiparametric inference for the parameter of interest when the model for one sample is parametric and that for the other is nonparametric. The parameter of interest may represent, for example, a comparison of means, or survival probabilities. The confidence interval derived from the semiparametric inference, which is based on the empirical likelihood principle, improves its counterpart constructed from the common estimating equation. The empirical likelihood ratio is shown to be asymptotically chi-squared. Simulation experiments illustrate that the method based on the empirical likelihood substantially outperforms the method based on the estimating equation. A real dataset is analysed.
doi:10.1093/biomet/92.2.271
PMCID: PMC2825713  PMID: 20179776
Estimating equation; Confidence interval; Coverage; Kaplan-Meier estimation; Empirical likelihood ratio; Empirical likelihood function
19.  On Estimation of Partially Linear Transformation Models 
We study a general class of partially linear transformation models, which extend linear transformation models by incorporating nonlinear covariate effects in survival data analysis. A new martingale-based estimating equation approach, consisting of both global and kernel-weighted local estimation equations, is developed for estimating the parametric and nonparametric covariate effects in a unified manner. We show that with a proper choice of the kernel bandwidth parameter, one can obtain the consistent and asymptotically normal parameter estimates for the linear effects. Asymptotic properties of the estimated nonlinear effects are established as well. We further suggest a simple resampling method to estimate the asymptotic variance of the linear estimates and show its effectiveness. To facilitate the implementation of the new procedure, an iterative algorithm is developed. Numerical examples are given to illustrate the finite-sample performance of the procedure.
doi:10.1198/jasa.2010.tm09302.
PMCID: PMC2929143  PMID: 20802823
Estimating equations; Local polynomials; Martingale; Partially linear transformation models; Resampling
20.  Sieve Maximum Likelihood Estimation for Doubly Semiparametric Zero-Inflated Poisson Models 
Journal of multivariate analysis  2010;101(9):2026-2038.
For nonnegative measurements such as income or sick days, zero counts often have special status. Furthermore, the incidence of zero counts is often greater than expected for the Poisson model. This article considers a doubly semiparametric zero-inflated Poisson model to fit data of this type, which assumes two partially linear link functions in both the mean of the Poisson component and the probability of zero. We study a sieve maximum likelihood estimator for both the regression parameters and the nonparametric functions. We show, under routine conditions, that the estimators are strongly consistent. Moreover, the parameter estimators are asymptotically normal and first-order efficient, while the nonparametric components achieve the optimal convergence rates. Simulation studies suggest that the extra flexibility inherent from the doubly semiparametric model is gained with little loss in statistical efficiency. We also illustrate our approach with a dataset from a public health study.
doi:10.1016/j.jmva.2010.05.003
PMCID: PMC2909790  PMID: 20671990
Asymptotic efficiency; Partly linear model; Sieve maximum likelihood estimator; Zero-inflated Poisson model
21.  A Generalized Gamma Mixture Model for Ultrasonic Tissue Characterization 
Several statistical models have been proposed in the literature to describe the behavior of speckles. Among them, the Nakagami distribution has proven to very accurately characterize the speckle behavior in tissues. However, it fails when describing the heavier tails caused by the impulsive response of a speckle. The Generalized Gamma (GG) distribution (which also generalizes the Nakagami distribution) was proposed to overcome these limitations. Despite the advantages of the distribution in terms of goodness of fitting, its main drawback is the lack of a closed-form maximum likelihood (ML) estimates. Thus, the calculation of its parameters becomes difficult and not attractive. In this work, we propose (1) a simple but robust methodology to estimate the ML parameters of GG distributions and (2) a Generalized Gama Mixture Model (GGMM). These mixture models are of great value in ultrasound imaging when the received signal is characterized by a different nature of tissues. We show that a better speckle characterization is achieved when using GG and GGMM rather than other state-of-the-art distributions and mixture models. Results showed the better performance of the GG distribution in characterizing the speckle of blood and myocardial tissue in ultrasonic images.
doi:10.1155/2012/481923
PMCID: PMC3529535  PMID: 23424602
22.  Efficient distribution estimation for data with unobserved sub-population identifiers 
We study efficient nonparametric estimation of distribution functions of several scientifically meaningful sub-populations from data consisting of mixed samples where the sub-population identifiers are missing. Only probabilities of each observation belonging to a sub-population are available. The problem arises from several biomedical studies such as quantitative trait locus (QTL) analysis and genetic studies with ungenotyped relatives where the scientific interest lies in estimating the cumulative distribution function of a trait given a specific genotype. However, in these studies subjects’ genotypes may not be directly observed. The distribution of the trait outcome is therefore a mixture of several genotype-specific distributions. We characterize the complete class of consistent estimators which includes members such as one type of nonparametric maximum likelihood estimator (NPMLE) and least squares or weighted least squares estimators. We identify the efficient estimator in the class that reaches the semiparametric efficiency bound, and we implement it using a simple procedure that remains consistent even if several components of the estimator are mis-specified. In addition, our close inspections on two commonly used NPMLEs in these problems show the surprising results that the NPMLE in one form is highly inefficient, while in the other form is inconsistent. We provide simulation procedures to illustrate the theoretical results and demonstrate the proposed methods through two real data examples.
doi:10.1214/12-EJS690
PMCID: PMC3685883  PMID: 23795232
Finite mixed samples; robustness; semiparametric efficiency; nonparametric maximum likelihood estimator (NPMLE)
23.  Modeling Sage data with a truncated gamma-Poisson model 
BMC Bioinformatics  2006;7:157.
Background
Serial Analysis of Gene Expressions (SAGE) produces gene expression measurements on a discrete scale, due to the finite number of molecules in the sample. This means that part of the variance in SAGE data should be understood as the sampling error in a binomial or Poisson distribution, whereas other variance sources, in particular biological variance, should be modeled using a continuous distribution function, i.e. a prior on the intensity of the Poisson distribution. One challenge is that such a model predicts a large number of genes with zero counts, which cannot be observed.
Results
We present a hierarchical Poisson model with a gamma prior and three different algorithms for estimating the parameters in the model. It turns out that the rate parameter in the gamma distribution can be estimated on the basis of a single SAGE library, whereas the estimate of the shape parameter becomes unstable. This means that the number of zero counts cannot be estimated reliably. When a bivariate model is applied to two SAGE libraries, however, the number of predicted zero counts becomes more stable and in approximate agreement with the number of transcripts observed across a large number of experiments. In all the libraries we analyzed there was a small population of very highly expressed tags, typically 1% of the tags, that could not be accounted for by the model. To handle those tags we chose to augment our model with a non-parametric component. We also show some results based on a log-normal distribution instead of the gamma distribution.
Conclusion
By modeling SAGE data with a hierarchical Poisson model it is possible to separate the sampling variance from the variance in gene expression. If expression levels are reported at the gene level rather than at the tag level, genes mapped to multiple tags must be kept separate, since their expression levels show a different statistical behavior. A log-normal prior provided a better fit to our data than the gamma prior, but except for a small subpopulation of tags with very high counts, the two priors are similar.
doi:10.1186/1471-2105-7-157
PMCID: PMC1479844  PMID: 16549008
24.  Quadratic Inference Functions for Varying Coefficient Models with Longitudinal Data 
Biometrics  2006;62(2):379-391.
Summary
Nonparametric smoothing methods are used to model longitudinal data, but the challenge remains to incorporate correlation into nonparametric estimation procedures. In this paper, we propose an efficient estimation procedure for varying coefficient models for longitudinal data. The proposed procedure can easily take into account correlation within subjects and directly deal with both continuous and discrete response longitudinal data under the framework of generalized linear models. Unlike the generalized estimation equation approach, the newly proposed procedure is more efficient when the working correlation is misspecified. For varying-coefficient models, it is often of interest to test whether coefficient functions are time-varying or time-invariant. We propose a unified and efficient nonparametric hypothesis testing procedure, and further demonstrate that the resulting test statistics have an asymptotic chi-squared distribution. In addition, the goodness-of-fit test is applied to test whether the model assumption is satisfied. The corresponding test is also useful for choosing basis functions and the number of knots for regression spline models in conjunction with the model selection criterion. We evaluate the finite sample performance of the proposed procedures with Monte Carlo simulation studies. The proposed methodology is illustrated by an analysis of a AIDS data set.
doi:10.1111/j.1541-0420.2005.00490.x
PMCID: PMC2680010  PMID: 16918902
Generalized method of moments; Goodness-of-fit; Model selection; Penalized spline; Quadratic inference function; Smoothing spline; Varying-coefficient model
25.  Bayesian semi-parametric analysis of Poisson change-point regression models: application to policy making in Cali, Colombia 
Journal of applied statistics  2012;39(10):2285-2298.
A Poisson regression model with an offset assumes a constant baseline rate after accounting for measured covariates, which may lead to biased estimates of coefficients in an inhomogeneous Poisson process. To correctly estimate the effect of time-dependent covariates, we propose a Poisson change-point regression model with an offset that allows a time-varying baseline rate. When the nonconstant pattern of a log baseline rate is modeled with a nonparametric step function, the resulting semi-parametric model involves a model component of varying dimension and thus requires a sophisticated varying-dimensional inference to obtain correct estimates of model parameters of fixed dimension. To fit the proposed varying-dimensional model, we devise a state-of-the-art MCMC-type algorithm based on partial collapse. The proposed model and methods are used to investigate an association between daily homicide rates in Cali, Colombia and policies that restrict the hours during which the legal sale of alcoholic beverages is permitted. While simultaneously identifying the latent changes in the baseline homicide rate which correspond to the incidence of sociopolitical events, we explore the effect of policies governing the sale of alcohol on homicide rates and seek a policy that balances the economic and cultural dependencies on alcohol sales to the health of the public.
doi:10.1080/02664763.2012.709227
PMCID: PMC3563101  PMID: 23393408
Bayesian analysis; change-point model; inhomogeneous Poisson process; Markov chain Monte Carlo; partial collapse; Poisson regression

Results 1-25 (497854)