No description available.

No description available.

O objetivo deste trabalho é estudar a performance de alguns métodos de comparações múltiplas (MCMs) que ajustam o valor-p quando as estatísticas empregadas nos testes são a log-rank e a Cramér-von Mises, ambas não paramétricas e com estrutura de dependência. A vantagem dos MCMs que ajustam o valor-p é que eles controlam as taxas de erro tipo I e tipo II para cada hipótese, afim de atingir um poder estatístico elevado, mantendo a taxa de erro da família dos testes (FWER) menor ou igual ao nível de significância escolhido. Trabalhamos com o procedimento clássico de Bonferroni e com outros métodos vistos como seu melhoramento, com especial atenção a certos procedimentos derivados do método de Simes que permitem realizar inferências sob as hipóteses individuais. Foi verificado teoricamente que a estatística log-rank pertence à classe multivariada totalmente positiva de ordem 2 (\'MTP IND. 2\'), uma vez que o método de Simes garante o controle da FWER quando as estatísticas dependentes assumem esta condição. O controle da FWER empregando a estatística de Cramér-von Mises foi observado apenas por meio de simulações. Os MCMs foram analisados através de estudos computacionais em modelos discretos e contínuos sob censura com foco no problema de comparar um tratamento versus controle / The aim of this work is to study the performance of some Multiple Comparison Methods (MCMs) that adjust the p-value when the log-rank-type and Cramér-von Mises statistics are used, both nonparametric and with dependency structure. The advantage of these methods is that they control the error rates of type I and type II for each hypothesis in order to achieve high statistical power while keeping the Family Wise Error Rate (FWER) lower or equal than a given significance level. The classical Bonferroni procedure is used as well as others seen as its improvement, with special attention to certain procedures derived from Simes\' method for making inferences on individual hypothesis. It is theoretically proved that the weighted Log-Rank statistics belongs to the multivariate totally positive of order 2 (\'MTP IND. 2\') class, which is needed in order to apply Simes\' method, that guarantees control of the FWER of dependent statistics in this case. The control of the FWER when the Cramér-von Mises statistics is used is only veried by means of computational simulations. The MCMs are also analyzed by means of computational experiments with discrete and continuous data under censoring with focus on the problem of comparisons of treatment versus a control

Cette thèse est motivée par l’analyse des données issues de l’imagerie par résonance magnétique fonctionnelle (IRMf). La nécessité de développer des méthodes capables d’extraire la structure sous-jacente des données d’IRMf constitue un challenge mathématique attractif. A cet égard, nous modélisons les réseaux de connectivité cérébrale par un graphe et nous étudions des procédures permettant d’inférer ce graphe.Plus précisément, nous nous intéressons à l’inférence de la structure d’un modèle graphique non orienté par une procédure de test multiple. Nous considérons deux types de structure, à savoir celle induite par la corrélation et celle induite par la corrélation partielle entre les variables aléatoires. Les statistiques de tests basées sur ces deux dernières mesures sont connues pour présenter une forte dépendance et nous les supposerons être asymptotiquement gaussiennes. Dans ce contexte, nous analysons plusieurs procédures de test multiple permettant un contrôle des arêtes incluses à tort dans le graphe inféré.Dans un premier temps, nous questionnons théoriquement le contrôle du False Discovery Rate (FDR) de la procédure de Benjamini et Hochberg dans un cadre gaussien pour des statistiques de test non nécessairement positivement dépendantes. Nous interrogeons par suite le contrôle du FDR et du Family Wise Error Rate (FWER) dans un cadre gaussien asymptotique. Nous présentons plusieurs procédures de test multiple, adaptées aux tests de corrélations (resp. corrélations partielles), qui contrôlent asymptotiquement le FWER. Nous proposons de plus quelques pistes théoriques relatives au contrôle asymptotique du FDR.Dans un second temps, nous illustrons les propriétés des procédures contrôlant asymptotiquement le FWER à travers une étude sur simulation pour des tests basés sur la corrélation. Nous concluons finalement par l’extraction de réseaux de connectivité cérébrale sur données réelles. / This thesis is motivated by the analysis of the functional magnetic resonance imaging (fMRI). The need for methods to build such structures from fMRI data gives rise to exciting new challenges for mathematics. In this regards, the brain connectivity networks are modelized by a graph and we study some procedures that allow us to infer this graph.More precisely, we investigate the problem of the inference of the structure of an undirected graphical model by a multiple testing procedure. The structure induced by both the correlation and the partial correlation are considered. The statistical tests based on the latter are known to be highly dependent and we assume that they have an asymptotic Gaussian distribution. Within this framework, we study some multiple testing procedures that allow a control of false edges included in the inferred graph.First, we theoretically examine the False Discovery Rate (FDR) control of Benjamini and Hochberg’s procedure in Gaussian setting for non necessary positive dependent statistical tests. Then, we explore both the FDR and the Family Wise Error Rate (FWER) control in asymptotic Gaussian setting. We present some multiple testing procedures, well-suited for correlation (resp. partial correlation) tests, which provide an asymptotic control of the FWER. Furthermore, some first theoretical results regarding asymptotic FDR control are established.Second, the properties of the multiple testing procedures that asymptotically control the FWER are illustrated on a simulation study, for statistical tests based on correlation. We finally conclude with the extraction of cerebral connectivity networks on real data set.

O objetivo deste trabalho é estudar a performance de alguns métodos de comparações múltiplas (MCMs) que ajustam o valor-p quando as estatísticas empregadas nos testes são a log-rank e a Cramér-von Mises, ambas não paramétricas e com estrutura de dependência. A vantagem dos MCMs que ajustam o valor-p é que eles controlam as taxas de erro tipo I e tipo II para cada hipótese, afim de atingir um poder estatístico elevado, mantendo a taxa de erro da família dos testes (FWER) menor ou igual ao nível de significância escolhido. Trabalhamos com o procedimento clássico de Bonferroni e com outros métodos vistos como seu melhoramento, com especial atenção a certos procedimentos derivados do método de Simes que permitem realizar inferências sob as hipóteses individuais. Foi verificado teoricamente que a estatística log-rank pertence à classe multivariada totalmente positiva de ordem 2 (\'MTP IND. 2\'), uma vez que o método de Simes garante o controle da FWER quando as estatísticas dependentes assumem esta condição. O controle da FWER empregando a estatística de Cramér-von Mises foi observado apenas por meio de simulações. Os MCMs foram analisados através de estudos computacionais em modelos discretos e contínuos sob censura com foco no problema de comparar um tratamento versus controle / The aim of this work is to study the performance of some Multiple Comparison Methods (MCMs) that adjust the p-value when the log-rank-type and Cramér-von Mises statistics are used, both nonparametric and with dependency structure. The advantage of these methods is that they control the error rates of type I and type II for each hypothesis in order to achieve high statistical power while keeping the Family Wise Error Rate (FWER) lower or equal than a given significance level. The classical Bonferroni procedure is used as well as others seen as its improvement, with special attention to certain procedures derived from Simes\' method for making inferences on individual hypothesis. It is theoretically proved that the weighted Log-Rank statistics belongs to the multivariate totally positive of order 2 (\'MTP IND. 2\') class, which is needed in order to apply Simes\' method, that guarantees control of the FWER of dependent statistics in this case. The control of the FWER when the Cramér-von Mises statistics is used is only veried by means of computational simulations. The MCMs are also analyzed by means of computational experiments with discrete and continuous data under censoring with focus on the problem of comparisons of treatment versus a control

No description available.

There are a number of available statistical methods for adaptive designs, among which the combination method of Bauer and Kohne's (1994) is well known and widely used. In this work, we revisit the the Bauer-Kohne method in three ways: overall FWER control for single-hypothesis in a two-stage adaptive design, overall FWER control for two-hypothesis in a two-stage adaptive design, and overall FDR control for multiple-hypothesis in a two-stage adaptive design. We first take the Bauer-Kohne method in a more direct manner to have more flexibility in the choice of the early rejection and acceptance boundaries as well as the second stage critical value based on the chosen combination function. Our goal is not to develop a new method, but focus primarily on developing a comprehensive understanding of two-stage designs. Rather than tying up the early rejection and acceptance boundaries by considering the second stage critical value to be the same as that of the level á combination test, as done in the original Bauer-Kohne method, we allow the second-stage critical value to be determined from prefixed early rejection and acceptance boundaries. An explicit formula is derived for the overall Type I error probability to determine the second stage critical value from these stopping boundaries not only for Fisher's combination function but also for other types of combination function. Tables of critical values corresponding to several different choices of early rejection and acceptance boundaries and these combination functions are presented. A dataset from a clinical study is used to apply the different methods based on directly computed second stage critical values from pre fixed stopping boundaries and discuss the outcomes in relation to those produced by the original Bauer-Kohne method. We then extend the Bauer-Kohne method to two-hypothesis setting and propose a stepwise-combination method for a two-stage adaptive design. In particular, we modify Holm's step-down procedure (1979) and suggest a step-down combination method to control the overall FWER at a desired level á. In many scientific studies requiring simultaneous testing of multiple null hypotheses, it is often necessary to carry out the multiple testing in two stages to decide which of the hypotheses can be rejected or accepted at the first stage and which should be followed up for further testing having combined their p-values from both stages. Unfortunately, no multiple testing procedure is available yet to perform this task meeting pre-specified boundaries on the first-stage p-values in terms of the false discovery rate (FDR) and maintaining a control over the overall FDR at a desired level. Our third goal in this work is to present two procedures, extending the classical Benjamini-Hochberg (BH) procedure and its adaptive version incorporating an estimate of the number of true null hypotheses from single-stage to a two-stage setting. These procedures are theoretically proved to control the overall FDR when the pairs of first- and second-stage p-values are independent and those corresponding to the null hypotheses are identically distributed as a pair (p1, p2) satisfying the p-clud property of Brannath, Posch and Bauer (2002, Journal of the American Statistical Association, 97, 236 -244). We consider two types of combination function, Fisher's and Simes', and present explicit formulas involving these functions towards carrying out the proposed procedures based on pre-determined critical values or through estimated FDR's. Simulations were carried to compare the proposed methods with class BH procedure using first stage data only and full data from both stages respectively. Our simulation studies indicate that the proposed procedures can have significant power improvement over the single-stage BH procedure based on the first stage data, at least under independence, and can continue to control the FDR under some dependence situations. Application of the proposed procedures to a real gene expression data set produces more discoveries compared to the single-stage BH procedure using the first stage data and full data as well. / Statistics

DNA microarrays are a relatively new technology for assessing the expression levels of thousands of genes simultaneously. Researchers hope to find genes that are differentially expressed by hybridizing cDNA from known treatment sources with various genes spotted on the microarrays. The large number of tests involved in analyzing microarrays has raised new questions in multiple testing. Several approaches for identifying differentially expressed genes have been proposed. This paper considers two: (1) a mixed models approach, and (2) the Signiffcance Analysis of Microarrays.

Considérons un vecteur gaussien Y de loi N (m,sigma²Idn) et X une matrice de dimension n x p avec Y observé, m inconnu, Sigma et X connus. Dans le cadre du modèle linéaire, m est supposé être une combinaison linéaire des colonnes de X. En petite dimension, lorsque n ≥ p et que ker (X) = 0, il existe alors un unique paramètre Beta* tel que m = X Beta* ; on peut alors réécrire Y sous la forme Y = X Beta* + Epsilon. Dans le cadre du modèle linéaire gaussien en petite dimension, nous construisons une nouvelle procédure de tests multiples contrôlant le FWER pour tester les hypothèses nulles Beta*i = 0 pour i appartient à [[1,p]]. Cette procédure est appliquée en métabolomique au travers du programme ASICS qui est disponible en ligne. ASICS permet d'identifier et de quantifier les métabolites via l'analyse des spectres RMN. En grande dimension, lorsque n < p on a ker (X) ≠ 0, ainsi le paramètre Beta* décrit précédemment n'est pas unique. Dans le cas non bruité lorsque Sigma = 0, impliquant que Y = m, nous montrons que les solutions du système linéaire d'équations Y = X Beta avant un nombre de composantes non nulles minimales s'obtiennent via la minimisation de la "norme" lAlpha avec Alpha suffisamment petit. / Let Y be a Gaussian vector distributed according to N (m,sigma²Idn) and X a matrix of dimension n x p with Y observed, m unknown, sigma and X known. In the linear model, m is assumed to be a linear combination of the columns of X In small dimension, when n ≥ p and ker (X) = 0, there exists a unique parameter Beta* such that m = X Beta*; then we can rewrite Y = Beta* + Epsilon. In the small-dimensional linear Gaussian model framework, we construct a new multiple testing procedure controlling the FWER to test the null hypotheses Beta*i = 0 for i belongs to [[1,p]]. This procedure is applied in metabolomics through the freeware ASICS available online. ASICS allows to identify and to qualify metabolites via the analyse of RMN spectra. In high dimension, when n < p we have ker (X) ≠ 0 consequently the parameter Beta* described above is no longer unique. In the noiseless case when Sigma = 0, implying thus Y = m, we show that the solutions of the linear system of equation Y = X Beta having a minimal number of non-zero components are obtained via the lalpha with alpha small enough.

No description available.