Statistical Theory Commons^™

Estimating Subject-Specific Dependent Competing Risk Profile With Censored Event Time Observations, Yi Li, Lu Tian, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Class Of Semiparametric Mixture Cure Survival Models With Dependent Censoring, Megan Othus, Yi Li, Ram C. Tiwari

Harvard University Biostatistics Working Paper Series

No abstract provided.

Joint Multiple Testing Procedures For Graphical Model Selection With Applications To Biological Networks, Houston N. Gilbert, Mark J. Van Der Laan, Sandrine Dudoit

U.C. Berkeley Division of Biostatistics Working Paper Series

Gaussian graphical models have become popular tools for identifying relationships between genes when analyzing microarray expression data. In the classical undirected Gaussian graphical model setting, conditional independence relationships can be inferred from partial correlations obtained from the concentration matrix (= inverse covariance matrix) when the sample size n exceeds the number of parameters p which need to estimated. In situations where n < p, another approach to graphical model estimation may rely on calculating unconditional (zero-order) and first-order partial correlations. In these settings, the goal is to identify a lower-order conditional independence graph, sometimes referred to as a ‘0-1 graphs’. For either choice of graph, model selection may involve a multiple testing problem, in which edges in a graph are drawn only after rejecting hypotheses involving (saturated or lower-order) partial correlation parameters. Most multiple testing procedures applied in previously proposed graphical model selection algorithms rely on standard, marginal testing methods which do not take into account the joint distribution of the test statistics derived from (partial) correlations. We propose and implement a multiple testing framework useful when testing for edge inclusion during graphical model selection. Two features of our methodology include (i) a computationally efficient and asymptotically valid test statistics joint null distribution derived from influence curves for correlation-based parameters, and (ii) the application of empirical Bayes joint multiple testing procedures which can effectively control a variety of popular Type I error rates by incorpo- rating joint null distributions such as those described here (Dudoit and van der Laan, 2008). Using a dataset from Arabidopsis thaliana, we observe that the use of more sophisticated, modular approaches to multiple testing allows one to identify greater numbers of edges when approximating an undirected graphical model using a 0-1 graph. Our framework may also be extended to edge testing algorithms for other types of graphical models (e.g., for classical undirected, bidirected, and directed acyclic graphs).

Analysis Of Randomized Comparative Clinical Trial Data For Personalized Treatment Selections, Tianxi Cai, Lu Tian, Peggy H. Wong, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Small Sample Correction For Estimating Attributable Risk In Case-Control Studies, Daniel B. Rubin

U.C. Berkeley Division of Biostatistics Working Paper Series

The attributable risk, often called the population attributable risk, is in many epidemiological contexts a more relevant measure of exposure-disease association than the excess risk, relative risk, or odds ratio. When estimating attributable risk with case-control data and a rare disease, we present a simple correction to the standard approach making it essentially unbiased, and also less noisy. As with analogous corrections given in Jewell (1986) for other measures of association, the adjustment often won't make a substantial difference unless the sample size is very small or point estimates are desired within fine strata, but we discuss the possible utility …

The Highest Confidence Density Region And Its Usage For Inferences About The Survival Function With Censored Data, Lu Tian, Rui Wang, Tianxi Cai, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

Calibrating Parametric Subject-Specific Risk Estimation, Tianxi Cai, Lu Tian, Hajime Uno, Scott D. Solomon, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

Evaluating Subject-Level Incremental Values Of New Markers For Risk Classification Rule, Tianxi Cai, Lu Tian, Donald M. Lloyd-Jones, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

Confidence Intervals For Negative Binomial Random Variables Of High Dispersion, David Shilane, Alan E. Hubbard, S N. Evans

U.C. Berkeley Division of Biostatistics Working Paper Series

This paper considers the problem of constructing confidence intervals for the mean of a Negative Binomial random variable based upon sampled data. When the sample size is large, we traditionally rely upon a Normal distribution approximation to construct these intervals. However, we demonstrate that the sample mean of highly dispersed Negative Binomials exhibits a slow convergence to the Normal in distribution as a function of the sample size. As a result, standard techniques (such as the Normal approximation and bootstrap) that construct confidence intervals for the mean will typically be too narrow and significantly undercover in the case of high …

Estimation And Testing For The Effect Of A Genetic Pathway On A Disease Outcome Using Logistic Kernel Machine Regression Via Logistic Mixed Models, Dawei Liu, Debashis Ghosh, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Powerful And Flexible Multilocus Association Test For Quantitative Traits, Lydia Coulter Kwee, Dawei Liu, Xihong Lin, Debashis Ghosh, Michael P. Epstein

Harvard University Biostatistics Working Paper Series

No abstract provided.

Nonparametric Regression Using Local Kernel Estimating Equations For Correlated Failure Time Data, Zhangsheng Yu, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Comparison Of Methods For Estimating The Causal Effect Of A Treatment In Randomized Clinical Trials Subject To Noncompliance, Rod Little, Qi Long, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

Semiparametric Maximum Likelihood Estimation In Normal Transformation Models For Bivariate Survival Data, Yi Li, Ross L. Prentice, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

Supervised Distance Matrices: Theory And Applications To Genomics, Katherine S. Pollard, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

We propose a new approach to studying the relationship between a very high dimensional random variable and an outcome. Our method is based on a novel concept, the supervised distance matrix, which quantifies pairwise similarity between variables based on their association with the outcome. A supervised distance matrix is derived in two stages. The first stage involves a transformation based on a particular model for association. In particular, one might regress the outcome on each variable and then use the residuals or the influence curve from each regression as a data transformation. In the second stage, a choice of distance …

Confidence Intervals For The Population Mean Tailored To Small Sample Sizes, With Applications To Survey Sampling, Michael Rosenblum, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

The validity of standard confidence intervals constructed in survey sampling is based on the central limit theorem. For small sample sizes, the central limit theorem may give a poor approximation, resulting in confidence intervals that are misleading. We discuss this issue and propose methods for constructing confidence intervals for the population mean tailored to small sample sizes.

We present a simple approach for constructing confidence intervals for the population mean based on tail bounds for the sample mean that are correct for all sample sizes. Bernstein's inequality provides one such tail bound. The resulting confidence intervals have guaranteed coverage probability …

Loss-Based Estimation With Evolutionary Algorithms And Cross-Validation, David Shilane, Richard H. Liang, Sandrine Dudoit

U.C. Berkeley Division of Biostatistics Working Paper Series

Many statistical inference methods rely upon selection procedures to estimate a parameter of the joint distribution of explanatory and outcome data, such as the regression function. Within the general framework for loss-based estimation of Dudoit and van der Laan, this project proposes an evolutionary algorithm (EA) as a procedure for risk optimization. We also analyze the size of the parameter space for polynomial regression under an interaction constraints along with constraints on either the polynomial or variable degree.

Comparing Trends In Cancer Rates Across Overlapping Regions, Yi Li, Ram C. Tiwari

Harvard University Biostatistics Working Paper Series

No abstract provided.

Assessment Of A Cgh-Based Genetic Instability, David A. Engler, Yiping Shen, J F. Gusella, Rebecca A. Betensky

Harvard University Biostatistics Working Paper Series

No abstract provided.

Survival Analysis With Large Dimensional Covariates: An Application In Microarray Studies, David A. Engler, Yi Li

Harvard University Biostatistics Working Paper Series

Use of microarray technology often leads to high-dimensional and low- sample size data settings. Over the past several years, a variety of novel approaches have been proposed for variable selection in this context. However, only a small number of these have been adapted for time-to-event data where censoring is present. Among standard variable selection methods shown both to have good predictive accuracy and to be computationally efficient is the elastic net penalization approach. In this paper, adaptation of the elastic net approach is presented for variable selection both under the Cox proportional hazards model and under an accelerated failure time …

Semiparametric Regression Of Multi-Dimensional Genetic Pathway Data: Least Squares Kernel Machines And Linear Mixed Models, Dawei Liu, Xihong Lin, Debashis Ghosh

Harvard University Biostatistics Working Paper Series

No abstract provided.

Predicting Future Responses Based On Possibly Misspecified Working Models, Tianxi Cai, Lu Tian, Scott D. Solomon, L.J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

Multiple Tests Of Association With Biological Annotation Metadata, Sandrine Dudoit, Sunduz Keles, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

We propose a general and formal statistical framework for the multiple tests of associations between known fixed features of a genome and unknown parameters of the distribution of variable features of this genome in a population of interest. The known fixed gene-annotation profiles, corresponding to the fixed features of the genome, may concern Gene Ontology (GO) annotation, pathway membership, regulation by particular transcription factors, nucleotide sequences, or protein sequences. The unknown gene-parameter profiles, corresponding to the variable features of the genome, may be, for example, regression coefficients relating genome-wide transcript levels or DNA copy numbers to possibly censored biological and …

Regression Analysis For The Partial Area Under The Roc Curve, Tianxi Cai, Lori E. Dodd

Harvard University Biostatistics Working Paper Series

No abstract provided.

Issues Of Processing And Multiple Testing Of Seldi-Tof Ms Proteomic Data, Merrill D. Birkner, Alan E. Hubbard, Mark J. Van Der Laan, Christine F. Skibola, Christine M. Hegedus, Martyn T. Smith

U.C. Berkeley Division of Biostatistics Working Paper Series

A new data filtering method for SELDI-TOF MS proteomic spectra data is described. We examined technical repeats (2 per subject) of intensity versus m/z (mass/charge) of bone marrow cell lysate for two groups of childhood leukemia patients: acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). As others have noted, the type of data processing as well as experimental variability can have a disproportionate impact on the list of "interesting" proteins (see Baggerly et al. (2004)). We propose a list of processing and multiple testing techniques to correct for 1) background drift; 2) filtering using smooth regression and cross-validated bandwidth …

Estimating A Treatment Effect With Repeated Measurements Accounting For Varying Effectiveness Duration, Ying Qing Chen, Jingrong Yang, Su-Chun Cheng

UW Biostatistics Working Paper Series

To assess treatment efficacy in clinical trials, certain clinical outcomes are repeatedly measured for same subject over time. They can be regarded as function of time. The difference in their mean functions between the treatment arms usually characterises a treatment effect. Due to the potential existence of subject-specific treatment effectiveness lag and saturation times, erosion of treatment effect in the difference may occur during the observation period of time. Instead of using ad hoc parametric or purely nonparametric time-varying coefficients in statistical modeling, we first propose to model the treatment effectiveness durations, which are the varying time intervals between the …

Population Intervention Models In Causal Inference, Alan E. Hubbard, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Marginal structural models (MSM) provide a powerful tool for estimating the causal effect of a] treatment variable or risk variable on the distribution of a disease in a population. These models, as originally introduced by Robins (e.g., Robins (2000a), Robins (2000b), van der Laan and Robins (2002)), model the marginal distributions of treatment-specific counterfactual outcomes, possibly conditional on a subset of the baseline covariates, and its dependence on treatment. Marginal structural models are particularly useful in the context of longitudinal data structures, in which each subject's treatment and covariate history are measured over time, and an outcome is recorded at …

A Pseudolikelihood Approach For Simultaneous Analysis Of Array Comparative Genomic Hybridizations (Acgh), David A. Engler, Gayatry Mohapatra, David N. Louis, Rebecca Betensky

Harvard University Biostatistics Working Paper Series

DNA sequence copy number has been shown to be associated with cancer development and progression. Array-based Comparative Genomic Hybridization (aCGH) is a recent development that seeks to identify the copy number ratio at large numbers of markers across the genome. Due to experimental and biological variations across chromosomes and across hybridizations, current methods are limited to analyses of single chromosomes. We propose a more powerful approach that borrows strength across chromosomes and across hybridizations. We assume a Gaussian mixture model, with a hidden Markov dependence structure, and with random effects to allow for intertumoral variation, as well as intratumoral clonal …

Direct Effect Models, Mark J. Van Der Laan, Maya L. Petersen

U.C. Berkeley Division of Biostatistics Working Paper Series

The causal effect of a treatment on an outcome is generally mediated by several intermediate variables. Estimation of the component of the causal effect of a treatment that is mediated by a given intermediate variable (the indirect effect of the treatment), and the component that is not mediated by that intermediate variable (the direct effect of the treatment) is often relevant to mechanistic understanding and to the design of clinical and public health interventions. Under the assumption of no-unmeasured confounders for treatment and the intermediate variable, Robins & Greenland (1992) define an individual direct effect as the counterfactual effect of …

Application Of A Multiple Testing Procedure Controlling The Proportion Of False Positives To Protein And Bacterial Data, Merrill D. Birkner, Alan E. Hubbard, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Simultaneously testing multiple hypotheses is important in high-dimensional biological studies. In these situations, one is often interested in controlling the Type-I error rate, such as the proportion of false positives to total rejections (TPPFP) at a specific level, alpha. This article will present an application of the E-Bayes/Bootstrap TPPFP procedure, presented in van der Laan et al. (2005), which controls the tail probability of the proportion of false positives (TPPFP), on two biological datasets. The two data applications include firstly, the application to a mass-spectrometry dataset of two leukemia subtypes, AML and ALL. The protein data measurements include intensity and …