A statistical test vs. a validation experiment in Gene Expression Study

Report published in the Proceedings of the National Conference on "Education and Research in the Information Society", Plovdiv, May, 2014

Harnessing the complexity of gene expression data from cancer: from single gene to structural pathway methods

High-dimensional gene expression data provide a rich source of information because they capture the expression level of genes in dynamic states that reflect the biological functioning of a cell. For this reason, such data are suitable to reveal systems related properties inside a cell, e.g., in order to elucidate molecular mechanisms of complex diseases like breast or prostate cancer. However, this is not only strongly dependent on the sample size and the correlation structure of a data set, but also on the statistical hypotheses tested. Many different approaches have been developed over the years to analyze gene expression data to (I) identify changes in single genes, (II) identify changes in gene sets or pathways, and (III) identify changes in the correlation structure in pathways. In this paper, we review statistical methods for all three types of approaches, including subtypes, in the context of cancer data and provide links to software implementations and tools and address also the general problem of multiple hypotheses testing. Further, we provide recommendations for the selection of such analysis methods.

Risk Aversion, Intertemporal Substitution, and Option Pricing

This paper develops a general stochastic framework and an equilibrium asset pricing model that make clear how attitudes towards intertemporal substitution and risk matter for option pricing. In particular, we show under which statistical conditions option pricing formulas are not preference-free, in other words, when preferences are not hidden in the stock and bond prices as they are in the standard Black and Scholes (BS) or Hull and White (HW) pricing formulas. The dependence of option prices on preference parameters comes from several instantaneous causality effects such as the so-called leverage effect. We also emphasize that the most standard asset pricing models (CAPM for the stock and BS or HW preference-free option pricing) are valid under the same stochastic setting (typically the absence of leverage effect), regardless of preference parameter values. Even though we propose a general non-preference-free option pricing formula, we always keep in mind that the BS formula is dominant both as a theoretical reference model and as a tool for practitioners. Another contribution of the paper is to characterize why the BS formula is such a benchmark. We show that, as soon as we are ready to accept a basic property of option prices, namely their homogeneity of degree one with respect to the pair formed by the underlying stock price and the strike price, the necessary statistical hypotheses for homogeneity provide BS-shaped option prices in equilibrium. This BS-shaped option-pricing formula allows us to derive interesting characterizations of the volatility smile, that is, the pattern of BS implicit volatilities as a function of the option moneyness. First, the asymmetry of the smile is shown to be equivalent to a particular form of asymmetry of the equivalent martingale measure. Second, this asymmetry appears precisely when there is either a premium on an instantaneous interest rate risk or on a generalized leverage effect or both, in other words, whenever the option pricing formula is not preference-free. Therefore, the main conclusion of our analysis for practitioners should be that an asymmetric smile is indicative of the relevance of preference parameters to price options.

An exploratory study of the effect of aspect-oriented programming on maintainability

In this paper we describe an exploratory assessment of the effect of aspect-oriented programming on software maintainability. An experiment was conducted in which 11 software professionals were asked to carry out maintenance tasks on one of two programs. The first program was written in Java and the second in AspectJ. Both programs implement a shopping system according to the same set of requirements. A number of statistical hypotheses were tested. The results did seem to suggest a slight advantage for the subjects using the object-oriented system since in general it took the subjects less time to answer the questions on this system. Also, both systems appeared to be equally difficult to modify. However, the results did not show a statistically significant influence of aspect-oriented programming at the 5% level. We are aware that the results of this single small study cannot be generalized. We conclude that more empirical research is necessary in this area to identify the benefits of aspect-oriented programming and we hope that this paper will encourage such research.

A new process capability index for multiple quality characteristics based on principal components

This paper presents a new multivariate process capability index (MPCI) which is based on the principal component analysis (PCA) and is dependent on a parameter (Formula presented.) which can take on any real number. This MPCI generalises some existing multivariate indices based on PCA proposed by several authors when (Formula presented.) or (Formula presented.). One of the key contributions of this paper is to show that there is a direct correspondence between this MPCI and process yield for a unique value of (Formula presented.). This result is used to establish a relationship between the capability status of the process and to show that under some mild conditions, the estimators of this MPCI is consistent and converge to a normal distribution. This is then applied to perform tests of statistical hypotheses and in determining sample sizes. Several numerical examples are presented with the objective of illustrating the procedures and demonstrating how they can be applied to determine the viability and capacity of different manufacturing processes.

Conducting statistical tests of hypotheses : five common misconceptions found in transportation research

Most statistical methods use hypothesis testing. Analysis of variance, regression, discrete choice models, contingency tables, and other analysis methods commonly used in transportation research share hypothesis testing as the means of making inferences about the population of interest. Despite the fact that hypothesis testing has been a cornerstone of empirical research for many years, various aspects of hypothesis tests commonly are incorrectly applied, misinterpreted, and ignored—by novices and expert researchers alike. On initial glance, hypothesis testing appears straightforward: develop the null and alternative hypotheses, compute the test statistic to compare to a standard distribution, estimate the probability of rejecting the null hypothesis, and then make claims about the importance of the finding. This is an oversimplification of the process of hypothesis testing. Hypothesis testing as applied in empirical research is examined here. The reader is assumed to have a basic knowledge of the role of hypothesis testing in various statistical methods. Through the use of an example, the mechanics of hypothesis testing is first reviewed. Then, five precautions surrounding the use and interpretation of hypothesis tests are developed; examples of each are provided to demonstrate how errors are made, and solutions are identified so similar errors can be avoided. Remedies are provided for common errors, and conclusions are drawn on how to use the results of this paper to improve the conduct of empirical research in transportation.

Statistical phylogeographic tests of competing 'Lake Carpentaria hypotheses' in the mouth-brooding freshwater fish, Glossamia aprion (Apogonidae)

Glacial cycles during the Pleistocene reduced sea levels and created new land connections in northern Australia, where many currently isolated rivers also became connected via an extensive paleo-lake system, 'Lake Carpentaria'. However, the most recent period during which populations of freshwater species were connected by gene flow across Lake Carpentaria is debated: various 'Lake Carpentaria hypotheses' have been proposed. Here, we used a statistical phylogeographic approach to assess the timing of past population connectivity across the Carpentaria region in the obligate freshwater fish, Glossamia aprion. Results for this species indicate that the most recent period of genetic exchange across the Carpentaria region coincided with the mid- to late Pleistocene, a result shown previously for other freshwater and diadromous species. Based on these findings and published studies for various freshwater, diadromous and marine species, we propose a set of 'Lake Carpentaria' hypotheses to explain past population connectivity in aquatic species: (1) strictly freshwater species had widespread gene flow in the mid- to late Pleistocene before the last glacial maximum; (2) marine species were subdivided into eastern and western populations by land during Pleistocene glacial phases; and (3) past connectivity in diadromous species reflects the relative strength of their marine affinity.

Notes on the theory of statistical estimation and of testing hypotheses : lectures /

"Notes prepared by Ralph J. Brookner."

The Impact of Indigenous status on adult sentencing : a review of the statistical research literature.

The gross overrepresentation of Indigenous peoples in prison populations suggests that sentencing may be a discriminatory process. Using findings from recent (1991–2011) multivariate statistical sentencing analyses from the United States, Canada, and Australia, we review the 3 key hypotheses advanced as plausible explanations for baseline sentencing discrepancies between Indigenous and non-Indigenous adult criminal defendants: (a) differential involvement, (b) negative discrimination, and (c) positive discrimination. Overall, the prior research shows strong support for the differential involvement thesis and some support for the discrimination theses (positive and negative). We argue that where discrimination is found, it may be explained by the lack of a more complete set of control variables in researchers’ multivariate models and/or differing political and social contexts.

A-SCALA: an age-structured statistical catch-at-length analysis for assessing tuna stocks in the eastern tropical Pacific Ocean

English: We describe an age-structured statistical catch-at-length analysis (A-SCALA) based on the MULTIFAN-CL model of Fournier et al. (1998). The analysis is applied independently to both the yellowfin and the bigeye tuna populations of the eastern Pacific Ocean (EPO). We model the populations from 1975 to 1999, based on quarterly time steps. Only a single stock for each species is assumed for each analysis, but multiple fisheries that are spatially separate are modeled to allow for spatial differences in catchability and selectivity. The analysis allows for error in the effort-fishing mortality relationship, temporal trends in catchability, temporal variation in recruitment, relationships between the environment and recruitment and between the environment and catchability, and differences in selectivity and catchability among fisheries. The model is fit to total catch data and proportional catch-at-length data conditioned on effort. The A-SCALA method is a statistical approach, and therefore recognizes that the data collected from the fishery do not perfectly represent the population. Also, there is uncertainty in our knowledge about the dynamics of the system and uncertainty about how the observed data relate to the real population. The use of likelihood functions allow us to model the uncertainty in the data collected from the population, and the inclusion of estimable process error allows us to model the uncertainties in the dynamics of the system. The statistical approach allows for the calculation of confidence intervals and the testing of hypotheses. We use a Bayesian version of the maximum likelihood framework that includes distributional constraints on temporal variation in recruitment, the effort-fishing mortality relationship, and catchability. Curvature penalties for selectivity parameters and penalties on extreme fishing mortality rates are also included in the objective function. The mode of the joint posterior distribution is used as an estimate of the model parameters. Confidence intervals are calculated using the normal approximation method. It should be noted that the estimation method includes constraints and priors and therefore the confidence intervals are different from traditionally calculated confidence intervals. Management reference points are calculated, and forward projections are carried out to provide advice for making management decisions for the yellowfin and bigeye populations. Spanish: Describimos un análisis estadístico de captura a talla estructurado por edad, A-SCALA (del inglés age-structured statistical catch-at-length analysis), basado en el modelo MULTIFAN- CL de Fournier et al. (1998). Se aplica el análisis independientemente a las poblaciones de atunes aleta amarilla y patudo del Océano Pacífico oriental (OPO). Modelamos las poblaciones de 1975 a 1999, en pasos trimestrales. Se supone solamente una sola población para cada especie para cada análisis, pero se modelan pesquerías múltiples espacialmente separadas para tomar en cuenta diferencias espaciales en la capturabilidad y selectividad. El análisis toma en cuenta error en la relación esfuerzo-mortalidad por pesca, tendencias temporales en la capturabilidad, variación temporal en el reclutamiento, relaciones entre el medio ambiente y el reclutamiento y entre el medio ambiente y la capturabilidad, y diferencias en selectividad y capturabilidad entre pesquerías. Se ajusta el modelo a datos de captura total y a datos de captura a talla proporcional condicionados sobre esfuerzo. El método A-SCALA es un enfoque estadístico, y reconoce por lo tanto que los datos obtenidos de la pesca no representan la población perfectamente. Además, hay incertidumbre en nuestros conocimientos de la dinámica del sistema e incertidumbre sobre la relación entre los datos observados y la población real. El uso de funciones de verosimilitud nos permite modelar la incertidumbre en los datos obtenidos de la población, y la inclusión de un error de proceso estimable nos permite modelar las incertidumbres en la dinámica del sistema. El enfoque estadístico permite calcular intervalos de confianza y comprobar hipótesis. Usamos una versión bayesiana del marco de verosimilitud máxima que incluye constreñimientos distribucionales sobre la variación temporal en el reclutamiento, la relación esfuerzo-mortalidad por pesca, y la capturabilidad. Se incluyen también en la función objetivo penalidades por curvatura para los parámetros de selectividad y penalidades por tasas extremas de mortalidad por pesca. Se usa la moda de la distribución posterior conjunta como estimación de los parámetros del modelo. Se calculan los intervalos de confianza usando el método de aproximación normal. Cabe destacar que el método de estimación incluye constreñimientos y distribuciones previas y por lo tanto los intervalos de confianza son diferentes de los intervalos de confianza calculados de forma tradicional. Se calculan puntos de referencia para el ordenamiento, y se realizan proyecciones a futuro para asesorar la toma de decisiones para el ordenamiento de las poblaciones de aleta amarilla y patudo.

Statistical hypothesis testing and common misinterpretations: should we abandon p-value in forensic science applications?

Many people regard the concept of hypothesis testing as fundamental to inferential statistics. Various schools of thought, in particular frequentist and Bayesian, have promoted radically different solutions for taking a decision about the plausibility of competing hypotheses. Comprehensive philosophical comparisons about their advantages and drawbacks are widely available and continue to span over large debates in the literature. More recently, controversial discussion was initiated by an editorial decision of a scientific journal [1] to refuse any paper submitted for publication containing null hypothesis testing procedures. Since the large majority of papers published in forensic journals propose the evaluation of statistical evidence based on the so called p-values, it is of interest to expose the discussion of this journal's decision within the forensic science community. This paper aims to provide forensic science researchers with a primer on the main concepts and their implications for making informed methodological choices.

Logique et tests d'hypotheses: reflexions sur les problemes mal poses en econometrie

Dans ce texte, nous analysons les développements récents de l’économétrie à la lumière de la théorie des tests statistiques. Nous revoyons d’abord quelques principes fondamentaux de philosophie des sciences et de théorie statistique, en mettant l’accent sur la parcimonie et la falsifiabilité comme critères d’évaluation des modèles, sur le rôle de la théorie des tests comme formalisation du principe de falsification de modèles probabilistes, ainsi que sur la justification logique des notions de base de la théorie des tests (tel le niveau d’un test). Nous montrons ensuite que certaines des méthodes statistiques et économétriques les plus utilisées sont fondamentalement inappropriées pour les problèmes et modèles considérés, tandis que de nombreuses hypothèses, pour lesquelles des procédures de test sont communément proposées, ne sont en fait pas du tout testables. De telles situations conduisent à des problèmes statistiques mal posés. Nous analysons quelques cas particuliers de tels problèmes : (1) la construction d’intervalles de confiance dans le cadre de modèles structurels qui posent des problèmes d’identification; (2) la construction de tests pour des hypothèses non paramétriques, incluant la construction de procédures robustes à l’hétéroscédasticité, à la non-normalité ou à la spécification dynamique. Nous indiquons que ces difficultés proviennent souvent de l’ambition d’affaiblir les conditions de régularité nécessaires à toute analyse statistique ainsi que d’une utilisation inappropriée de résultats de théorie distributionnelle asymptotique. Enfin, nous soulignons l’importance de formuler des hypothèses et modèles testables, et de proposer des techniques économétriques dont les propriétés sont démontrables dans les échantillons finis.

Identification, Weak Instruments and Statistical Inference in Econometrics

We discuss statistical inference problems associated with identification and testability in econometrics, and we emphasize the common nature of the two issues. After reviewing the relevant statistical notions, we consider in turn inference in nonparametric models and recent developments on weakly identified models (or weak instruments). We point out that many hypotheses, for which test procedures are commonly proposed, are not testable at all, while some frequently used econometric methods are fundamentally inappropriate for the models considered. Such situations lead to ill-defined statistical problems and are often associated with a misguided use of asymptotic distributional results. Concerning nonparametric hypotheses, we discuss three basic problems for which such difficulties occur: (1) testing a mean (or a moment) under (too) weak distributional assumptions; (2) inference under heteroskedasticity of unknown form; (3) inference in dynamic models with an unlimited number of parameters. Concerning weakly identified models, we stress that valid inference should be based on proper pivotal functions —a condition not satisfied by standard Wald-type methods based on standard errors — and we discuss recent developments in this field, mainly from the viewpoint of building valid tests and confidence sets. The techniques discussed include alternative proposed statistics, bounds, projection, split-sampling, conditioning, Monte Carlo tests. The possibility of deriving a finite-sample distributional theory, robustness to the presence of weak instruments, and robustness to the specification of a model for endogenous explanatory variables are stressed as important criteria assessing alternative procedures.

Statistical Object Recognition

Two formulations of model-based object recognition are described. MAP Model Matching evaluates joint hypotheses of match and pose, while Posterior Marginal Pose Estimation evaluates the pose only. Local search in pose space is carried out with the Expectation--Maximization (EM) algorithm. Recognition experiments are described where the EM algorithm is used to refine and evaluate pose hypotheses in 2D and 3D. Initial hypotheses for the 2D experiments were generated by a simple indexing method: Angle Pair Indexing. The Linear Combination of Views method of Ullman and Basri is employed as the projection model in the 3D experiments.

Compositional hypotheses of subcompositional stability and specific perturbation change and their testing

In standard multivariate statistical analysis common hypotheses of interest concern changes in mean vectors and subvectors. In compositional data analysis it is now well established that compositional change is most readily described in terms of the simplicial operation of perturbation and that subcompositions replace the marginal concept of subvectors. To motivate the statistical developments of this paper we present two challenging compositional problems from food production processes. Against this background the relevance of perturbations and subcompositions can be clearly seen. Moreover we can identify a number of hypotheses of interest involving the specification of particular perturbations or differences between perturbations and also hypotheses of subcompositional stability. We identify the two problems as being the counterpart of the analysis of paired comparison or split plot experiments and of separate sample comparative experiments in the jargon of standard multivariate analysis. We then develop appropriate estimation and testing procedures for a complete lattice of relevant compositional hypotheses