Novel Statistical Methods in Quantitative Genetics : Modeling Genetic Variance for Quantitative Trait Loci Mapping and Genomic Evaluation

This thesis develops and evaluates statistical methods for different types of genetic analyses, including quantitative trait loci (QTL) analysis, genome-wide association study (GWAS), and genomic evaluation. The main contribution of the thesis is to provide novel insights in modeling genetic variance, especially via random effects models. In variance component QTL analysis, a full likelihood model accounting for uncertainty in the identity-by-descent (IBD) matrix was developed. It was found to be able to correctly adjust the bias in genetic variance component estimation and gain power in QTL mapping in terms of precision.  Double hierarchical generalized linear models, and a non-iterative simplified version, were implemented and applied to fit data of an entire genome. These whole genome models were shown to have good performance in both QTL mapping and genomic prediction. A re-analysis of a publicly available GWAS data set identified significant loci in Arabidopsis that control phenotypic variance instead of mean, which validated the idea of variance-controlling genes.  The works in the thesis are accompanied by R packages available online, including a general statistical tool for fitting random effects models (hglm), an efficient generalized ridge regression for high-dimensional data (bigRR), a double-layer mixed model for genomic data analysis (iQTL), a stochastic IBD matrix calculator (MCIBD), a computational interface for QTL mapping (qtl.outbred), and a GWAS analysis tool for mapping variance-controlling loci (vGWAS).

Genetic heterogeneity of within-family variance of body weight in Atlantic salmon (Salmo salar)

BACKGROUND: Canalization is defined as the stability of a genotype against minor variations in both environment and genetics. Genetic variation in degree of canalization causes heterogeneity of within-family variance. The aims of this study are twofold: (1) quantify genetic heterogeneity of (within-family) residual variance in Atlantic salmon and (2) test whether the observed heterogeneity of (within-family) residual variance can be explained by simple scaling effects. RESULTS: Analysis of body weight in Atlantic salmon using a double hierarchical generalized linear model (DHGLM) revealed substantial heterogeneity of within-family variance. The 95% prediction interval for within-family variance ranged from ~0.4 to 1.2 kg2, implying that the within-family variance of the most extreme high families is expected to be approximately three times larger than the extreme low families. For cross-sectional data, DHGLM with an animal mean sub-model resulted in severe bias, while a corresponding sire-dam model was appropriate. Heterogeneity of variance was not sensitive to Box-Cox transformations of phenotypes, which implies that heterogeneity of variance exists beyond what would be expected from simple scaling effects. CONCLUSIONS: Substantial heterogeneity of within-family variance was found for body weight in Atlantic salmon. A tendency towards higher variance with higher means (scaling effects) was observed, but heterogeneity of within-family variance existed beyond what could be explained by simple scaling effects. For cross-sectional data, using the animal mean sub-model in the DHGLM resulted in biased estimates of variance components, which differed substantially both from a standard linear mean animal model and a sire-dam DHGLM model. Although genetic differences in canalization were observed, selection for increased canalization is difficult, because there is limited individual information for the variance sub-model, especially when based on cross-sectional data. Furthermore, potential macro-environmental changes (diet, climatic region, etc.) may make genetic heterogeneity of variance a less stable trait over time and space.

Non-monotone insurance contracts and their empirical consequences

The goal of this paper is to show the possibility of a non-monotone relation between coverage ans risk which has been considered in the literature of insurance models since the work of Rothschild and Stiglitz (1976). We present an insurance model where the insured agents have heterogeneity in risk aversion and in lenience (a prevention cost parameter). Risk aversion is described by a continuous parameter which is correlated with lenience and for the sake of simplicity, we assume perfect correlation. In the case of positive correlation, the more risk averse agent has higher cosr of prevention leading to a higher demand for coverage. Equivalently, the single crossing property (SCP) is valid and iplies a positive correlation between overage and risk in equilibrium. On the other hand, if the correlation between risk aversion and lenience is negative, not only may the SCP be broken, but also the monotonocity of contracts, i.e., the prediction that high (low) risk averse types choose full (partial) insurance. In both cases riskiness is monotonic in risk aversion, but in the last case there are some coverage levels associated with two different risks (low and high), which implies that the ex-ante (with respect to the risk aversion distribution) correlation between coverage and riskiness may have every sign (even though the ex-post correlation is always positive). Moreover, using another instrument (a proxy for riskiness), we give a testable implication to desentangle single crossing ans non single croosing under an ex-post zero correlation result: the monotonicity of coverage as a function os riskiness. Since by controlling for risk aversion (no asymmetric information), coverage is monotone function of riskiness, this also fives a test for asymmetric information. Finally, we relate this theoretical results to empirical tests in the recent literature, specially the Dionne, Gouruéroux and Vanasse (2001) work. In particular, they found an empirical evidence that seems to be compatible with asymmetric information and non single crossing in our framework. More generally, we build a hidden information model showing how omitted variables (asymmetric information) can bias the sign of the correlation of equilibrium variables conditioning on all observable variables. We show that this may be the case when the omitted variables have a non-monotonic relation with the observable ones. Moreover, because this non-dimensional does not capture this deature. Hence, our main results is to point out the importance of the SPC in testing predictions of the hidden information models.

Non-monotone insurence contracts and their empirical consequences

The goal of t.his paper is to show the possibility of a non-monot.one relation between coverage and risk which has been considered in the literature of insurance models since the work of Rothschild and Stiglitz (1976). We present an insurance model where the insured agents have heterogeneity in risk aversion and in lenience (a prevention cost parameter). Risk aversion is described by a continuou.'l parameter which is correlated with lenience and, for the sake of simplicity, we assume perfect correlation. In the case of positive correlation, the more risk averse agent has higher cost of prevention leading to a higher demand for coverage. Equivalently, the single crossing property (SCP) is valid and implies a positive correlation between coverage and risk in equilibrium. On the other hand, if the correlation between risk aversion and lenience is negative, not only may the sep be broken, but also the monotonicity of contracts, i.e., the prediction that high (Iow) risk averse types choose full (partial) insurance. In both cases riskiness is monotonic in risk aversion, but in the last case t,here are some coverage leveIs associated with two different risks (low and high), which implies that the ex-ante (with respect to the risk aversion distribution) correlation bet,ween coverage and riskiness may have every sign (even though the ex-post correlation is always positive). Moreover, using another instrument (a proxy for riskiness), we give a testable implication to disentangle single crossing and non single crossing under an ex-post zero correlation result: the monotonicity of coverage as a function of riskiness. Since by controlling for risk aversion (no asymmetric informat, ion), coverage is a monotone function of riskiness, this also gives a test for asymmetric information. Finally, we relate this theoretical results to empirica! tests in the recent literature, specially the Dionne, Gouriéroux and Vanasse (2001) work. In particular, they found an empirical evidence that seems to be compatible with asymmetric information and non single crossing in our framework. More generally, we build a hidden information model showing how omitted variabIes (asymmetric information) can bias the sign of the correlation of equilibrium variabIes conditioning on ali observabIe variabIes. We show that this may be t,he case when the omitted variabIes have a non-monotonic reIation with t,he observable ones. Moreover, because this non-monotonic reIat,ion is deepIy reIated with the failure of the SCP in one-dimensional screening problems, the existing lit.erature on asymmetric information does not capture t,his feature. Hence, our main result is to point Out the importance of t,he SCP in testing predictions of the hidden information models.

A estrutura hierárquica das variações de preços e o núcleo da inflação

The approach proposed here explores the hierarchical nature of item-level data on price changes. On one hand, price data is naturally organized around a regional strucuture, with variations being observed on separate cities. Moreover, the itens that comprise the natural structure of CPIs are also normally interpreted in terms of groups that have economic interpretations, such as tradables and non-tradables, energyrelated, raw foodstuff, monitored prices, etc. The hierarchical dynamic factor model allow the estimation of multiple factors that are naturally interpreted as relating to each of these regional and economic levels.

H-N2N : uma arquitetura hierárquica escalável para ambientes de realidade mista de grande porte

In this work, we propose a solution to solve the scalability problem found in collaborative, virtual and mixed reality environments of large scale, that use the hierarchical client-server model. Basically, we use a hierarchy of servers. When the capacity of a server is reached, a new server is created as a sun of the first one, and the system load is distributed between them (father and sun). We propose efficient tools and techniques for solving problems inherent to client-server model, as the definition of clusters of users, distribution and redistribution of users through the servers, and some mixing and filtering operations, that are necessary to reduce flow between servers. The new model was tested, in simulation, emulation and in interactive applications that were implemented. The results of these experimentations show enhancements in the traditional, previous models indicating the usability of the proposed in problems of all-to-all communications. This is the case of interactive games and other applications devoted to Internet (including multi-user environments) and interactive applications of the Brazilian Digital Television System, to be developed by the research group. Keywords: large scale virtual environments, interactive digital tv, distributed

Distributed generators as providers of reactive power support - A market approach

Traditionally, ancillary services are supplied by large conventional generators. However, with the huge penetration of distributed generators (DGs) as a result of the growing interest in satisfying energy requirements, and considering the benefits that they can bring along to the electrical system and to the environment, it appears reasonable to assume that ancillary services could also be provided by DGs in an economical and efficient way. In this paper, a settlement procedure for a reactive power market for DGs in distribution systems is proposed. Attention is directed to wind turbines connected to the network through synchronous generators with permanent magnets and doubly-fed induction generators. The generation uncertainty of this kind of DG is reduced by running a multi-objective optimization algorithm in multiple probabilistic scenarios through the Monte Carlo method and by representing the active power generated by the DGs through Markov models. The objectives to be minimized are the payments of the distribution system operator to the DGs for reactive power, the curtailment of transactions committed in an active power market previously settled, the losses in the lines of the network, and a voltage profile index. The proposed methodology was tested using a modified IEEE 37-bus distribution test system. © 1969-2012 IEEE.

Conversão grafema-fone para um sistema de reconhecimento de voz com suporte a grandes vocabulários para o português brasileiro

O processamento de voz tornou-se uma tecnologia cada vez mais baseada na modelagem automática de vasta quantidade de dados. Desta forma, o sucesso das pesquisas nesta área está diretamente ligado a existência de corpora de domínio público e outros recursos específicos, tal como um dicionário fonético. No Brasil, ao contrário do que acontece para a língua inglesa, por exemplo, não existe atualmente em domínio público um sistema de Reconhecimento Automático de Voz (RAV) para o Português Brasileiro com suporte a grandes vocabulários. Frente a este cenário, o trabalho tem como principal objetivo discutir esforços dentro da iniciativa FalaBrasil [1], criada pelo Laboratório de Processamento de Sinais (LaPS) da UFPA, apresentando pesquisas e softwares na área de RAV para o Português do Brasil. Mais especificamente, o presente trabalho discute a implementação de um sistema de reconhecimento de voz com suporte a grandes vocabulários para o Português do Brasil, utilizando a ferramenta HTK baseada em modelo oculto de Markov (HMM) e a criação de um módulo de conversão grafema-fone, utilizando técnicas de aprendizado de máquina.

Ferramentas e recursos livres para reconhecimento e síntese de voz em português brasileiro

Sistemas de reconhecimento e síntese de voz são constituídos por módulos que dependem da língua e, enquanto existem muitos recursos públicos para alguns idiomas (p.e. Inglês e Japonês), os recursos para Português Brasileiro (PB) ainda são escassos. Outro aspecto é que, para um grande número de tarefas, a taxa de erro dos sistemas de reconhecimento de voz atuais ainda é elevada, quando comparada à obtida por seres humanos. Assim, apesar do sucesso das cadeias escondidas de Markov (HMM), é necessária a pesquisa por novos métodos. Este trabalho tem como motivação esses dois fatos e se divide em duas partes. A primeira descreve o desenvolvimento de recursos e ferramentas livres para reconhecimento e síntese de voz em PB, consistindo de bases de dados de áudio e texto, um dicionário fonético, um conversor grafema-fone, um separador silábico e modelos acústico e de linguagem. Todos os recursos construídos encontram-se publicamente disponíveis e, junto com uma interface de programação proposta, têm sido usados para o desenvolvimento de várias novas aplicações em tempo-real, incluindo um módulo de reconhecimento de voz para a suíte de aplicativos para escritório OpenOffice.org. São apresentados testes de desempenho dos sistemas desenvolvidos. Os recursos aqui produzidos e disponibilizados facilitam a adoção da tecnologia de voz para PB por outros grupos de pesquisa, desenvolvedores e pela indústria. A segunda parte do trabalho apresenta um novo método para reavaliar (rescoring) o resultado do reconhecimento baseado em HMMs, o qual é organizado em uma estrutura de dados do tipo lattice. Mais especificamente, o sistema utiliza classificadores discriminativos que buscam diminuir a confusão entre pares de fones. Para cada um desses problemas binários, são usadas técnicas de seleção automática de parâmetros para escolher a representaçãao paramétrica mais adequada para o problema em questão.

Reconhecimento de voz para aplicações em automação implementado em FPGA

In many movies of scientific fiction, machines were capable of speaking with humans. However mankind is still far away of getting those types of machines, like the famous character C3PO of Star Wars. During the last six decades the automatic speech recognition systems have been the target of many studies. Throughout these years many technics were developed to be used in applications of both software and hardware. There are many types of automatic speech recognition system, among which the one used in this work were the isolated word and independent of the speaker system, using Hidden Markov Models as the recognition system. The goals of this work is to project and synthesize the first two steps of the speech recognition system, the steps are: the speech signal acquisition and the pre-processing of the signal. Both steps were developed in a reprogrammable component named FPGA, using the VHDL hardware description language, owing to the high performance of this component and the flexibility of the language. In this work it is presented all the theory of digital signal processing, as Fast Fourier Transforms and digital filters and also all the theory of speech recognition using Hidden Markov Models and LPC processor. It is also presented all the results obtained for each one of the blocks synthesized e verified in hardware

An evolutionary approach to improve connectivity prediction in mobile wireless sensor networks

Connectivity is the basic factor for the proper operation of any wireless network. In a mobile wireless sensor network it is a challenge for applications and protocols to deal with connectivity problems, as links might get up and down frequently. In these scenarios, having knowledge of the node remaining connectivity time could both improve the performance of the protocols (e.g. handoff mechanisms) and save possible scarce nodes resources (CPU, bandwidth, and energy) by preventing unfruitful transmissions. The current paper provides a solution called Genetic Machine Learning Algorithm (GMLA) to forecast the remainder connectivity time in mobile environments. It consists in combining Classifier Systems with a Markov chain model of the RF link quality. The main advantage of using an evolutionary approach is that the Markov model parameters can be discovered on-the-fly, making it possible to cope with unknown environments and mobility patterns. Simulation results show that the proposal is a very suitable solution, as it overcomes the performance obtained by similar approaches.

Using Threads to Overcome Synchronization Delays in Parallel Multiple Progressive Alignment Algorithms

Sao Paulo State Research Foundation-FAPESP

Avaliação psicométrica da escala de atitudes em relação à estatística

RESUMO: O objetivo do estudo foi estimar a validade e confiabilidade da Escala de atitudes em relação à Estatística (EAE) quando aplicada a estudantes de Ciências Farmacêuticas. A amostra de 253 estudantes foi subdividida em duas partes. Sessenta por cento da amostra foi utilizada para explorar a estrutura fatorial e 40% para confirmá-la. Para verificar a reprodutibilidade da escala a mesma foi aplicada em duplicata a 40 estudantes. Aplicou-se o Teste de esfericidade de Bartlett e o índice Kaiser-Meyer-Olkin (KMO). A extração dos fatores foi realizada pela Análise de Componentes Principais. Realizou-se rotação ortogonal Varimax. Calculou-se o Coeficiente alfa de Cronbach (α) e o Coeficiente de Correlação Intraclasse (ρ). Realizou-se análise fatorial confirmatória. Elaborou-se um modelo hierárquico de segunda ordem (MHSO). O teste de esfericidade de Bartlett e o índice KMO foram excelentes (χ 2 =1835,815, p<0,001; KMO=0,935). Verificou-se dois fatores com valores próprios acima de 1 (λ=9,748; λ=2,086) explicando 59,2% da variância total. A questão 2 foi removida. Observou-se excelente consistência interna e reprodutibilidade. O modelo fatorial apresentou índices de qualidade de ajustamento bons (λ=0,59-0,86, χ 2 /gl=1,691, CFI=0,919, GFI=0,804, RMSEA=0,079). A validade discriminante dos fatores foi adequada. A EAE apresentou estrutura bifatorial na amostra com níveis de validade e confiabilidade adequados.

Learning HMMs for nucleotide sequences from amino acid alignments

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A avaliação da efetividade de um modelo de intervenção breve (método BASICS) para o uso de risco de álcool em estudantes do ensino médio

Pós-graduação em Saúde Coletiva - FMB