Massively parallelizable list-mode reconstruction using a Monte Carlo-based elliptical Gaussian model

Purpose: A fully three-dimensional (3D) massively parallelizable list-mode ordered-subsets expectation-maximization (LM-OSEM) reconstruction algorithm has been developed for high-resolution PET cameras. System response probabilities are calculated online from a set of parameters derived from Monte Carlo simulations. The shape of a system response for a given line of response (LOR) has been shown to be asymmetrical around the LOR. This work has been focused on the development of efficient region-search techniques to sample the system response probabilities, which are suitable for asymmetric kernel models, including elliptical Gaussian models that allow for high accuracy and high parallelization efficiency. The novel region-search scheme using variable kernel models is applied in the proposed PET reconstruction algorithm. Methods: A novel region-search technique has been used to sample the probability density function in correspondence with a small dynamic subset of the field of view that constitutes the region of response (ROR). The ROR is identified around the LOR by searching for any voxel within a dynamically calculated contour. The contour condition is currently defined as a fixed threshold over the posterior probability, and arbitrary kernel models can be applied using a numerical approach. The processing of the LORs is distributed in batches among the available computing devices, then, individual LORs are processed within different processing units. In this way, both multicore and multiple many-core processing units can be efficiently exploited. Tests have been conducted with probability models that take into account the noncolinearity, positron range, and crystal penetration effects, that produced tubes of response with varying elliptical sections whose axes were a function of the crystal's thickness and angle of incidence of the given LOR. The algorithm treats the probability model as a 3D scalar field defined within a reference system aligned with the ideal LOR. Results: This new technique provides superior image quality in terms of signal-to-noise ratio as compared with the histogram-mode method based on precomputed system matrices available for a commercial small animal scanner. Reconstruction times can be kept low with the use of multicore, many-core architectures, including multiple graphic processing units. Conclusions: A highly parallelizable LM reconstruction method has been proposed based on Monte Carlo simulations and new parallelization techniques aimed at improving the reconstruction speed and the image signal-to-noise of a given OSEM algorithm. The method has been validated using simulated and real phantoms. A special advantage of the new method is the possibility of defining dynamically the cut-off threshold over the calculated probabilities thus allowing for a direct control on the trade-off between speed and quality during the reconstruction.

Imputação de dados em experimentos multiambientais: novos algoritmos utilizando a decomposição por valores singulares

As análises biplot que utilizam os modelos de efeitos principais aditivos com inter- ação multiplicativa (AMMI) requerem matrizes de dados completas, mas, frequentemente os ensaios multiambientais apresentam dados faltantes. Nesta tese são propostas novas metodologias de imputação simples e múltipla que podem ser usadas para analisar da- dos desbalanceados em experimentos com interação genótipo por ambiente (G×E). A primeira, é uma nova extensão do método de validação cruzada por autovetor (Bro et al, 2008). A segunda, corresponde a um novo algoritmo não-paramétrico obtido por meio de modificações no método de imputação simples desenvolvido por Yan (2013). Também é incluído um estudo que considera sistemas de imputação recentemente relatados na literatura e os compara com o procedimento clássico recomendado para imputação em ensaios (G×E), ou seja, a combinação do algoritmo de Esperança-Maximização com os modelos AMMI ou EM-AMMI. Por último, são fornecidas generalizações da imputação simples descrita por Arciniegas-Alarcón et al. (2010) que mistura regressão com aproximação de posto inferior de uma matriz. Todas as metodologias têm como base a decomposição por valores singulares (DVS), portanto, são livres de pressuposições distribucionais ou estruturais. Para determinar o desempenho dos novos esquemas de imputação foram realizadas simulações baseadas em conjuntos de dados reais de diferentes espécies, com valores re- tirados aleatoriamente em diferentes porcentagens e a qualidade das imputações avaliada com distintas estatísticas. Concluiu-se que a DVS constitui uma ferramenta útil e flexível na construção de técnicas eficientes que contornem o problema de perda de informação em matrizes experimentais.

Successive nonparametric estimation of conditional distributions

Spatial characterization of non-Gaussian attributes in earth sciences and engineering commonly requires the estimation of their conditional distribution. The indicator and probability kriging approaches of current nonparametric geostatistics provide approximations for estimating conditional distributions. They do not, however, provide results similar to those in the cumbersome implementation of simultaneous cokriging of indicators. This paper presents a new formulation termed successive cokriging of indicators that avoids the classic simultaneous solution and related computational problems, while obtaining equivalent results to the impractical simultaneous solution of cokriging of indicators. A successive minimization of the estimation variance of probability estimates is performed, as additional data are successively included into the estimation process. In addition, the approach leads to an efficient nonparametric simulation algorithm for non-Gaussian random functions based on residual probabilities.

A Mixture model with random-effects components for clustering correlated gene-expression profiles

Motivation: The clustering of gene profiles across some experimental conditions of interest contributes significantly to the elucidation of unknown gene function, the validation of gene discoveries and the interpretation of biological processes. However, this clustering problem is not straightforward as the profiles of the genes are not all independently distributed and the expression levels may have been obtained from an experimental design involving replicated arrays. Ignoring the dependence between the gene profiles and the structure of the replicated data can result in important sources of variability in the experiments being overlooked in the analysis, with the consequent possibility of misleading inferences being made. We propose a random-effects model that provides a unified approach to the clustering of genes with correlated expression levels measured in a wide variety of experimental situations. Our model is an extension of the normal mixture model to account for the correlations between the gene profiles and to enable covariate information to be incorporated into the clustering process. Hence the model is applicable to longitudinal studies with or without replication, for example, time-course experiments by using time as a covariate, and to cross-sectional experiments by using categorical covariates to represent the different experimental classes. Results: We show that our random-effects model can be fitted by maximum likelihood via the EM algorithm for which the E(expectation) and M(maximization) steps can be implemented in closed form. Hence our model can be fitted deterministically without the need for time-consuming Monte Carlo approximations. The effectiveness of our model-based procedure for the clustering of correlated gene profiles is demonstrated on three real datasets, representing typical microarray experimental designs, covering time-course, repeated-measurement and cross-sectional data. In these examples, relevant clusters of the genes are obtained, which are supported by existing gene-function annotation. A synthetic dataset is considered too.

An Incremental EM-based Learning Approach for On-Line Prediction of Hospital Resource Utilization

Objective: Inpatient length of stay (LOS) is an important measure of hospital activity, health care resource consumption, and patient acuity. This research work aims at developing an incremental expectation maximization (EM) based learning approach on mixture of experts (ME) system for on-line prediction of LOS. The use of a batchmode learning process in most existing artificial neural networks to predict LOS is unrealistic, as the data become available over time and their pattern change dynamically. In contrast, an on-line process is capable of providing an output whenever a new datum becomes available. This on-the-spot information is therefore more useful and practical for making decisions, especially when one deals with a tremendous amount of data. Methods and material: The proposed approach is illustrated using a real example of gastroenteritis LOS data. The data set was extracted from a retrospective cohort study on all infants born in 1995-1997 and their subsequent admissions for gastroenteritis. The total number of admissions in this data set was n = 692. Linked hospitalization records of the cohort were retrieved retrospectively to derive the outcome measure, patient demographics, and associated co-morbidities information. A comparative study of the incremental learning and the batch-mode learning algorithms is considered. The performances of the learning algorithms are compared based on the mean absolute difference (MAD) between the predictions and the actual LOS, and the proportion of predictions with MAD < 1 day (Prop(MAD < 1)). The significance of the comparison is assessed through a regression analysis. Results: The incremental learning algorithm provides better on-line prediction of LOS when the system has gained sufficient training from more examples (MAD = 1.77 days and Prop(MAD < 1) = 54.3%), compared to that using the batch-mode learning. The regression analysis indicates a significant decrease of MAD (p-value = 0.063) and a significant (p-value = 0.044) increase of Prop(MAD

Multilevel modelling for inference of genetic regulatory networks

Time-course experiments with microarrays are often used to study dynamic biological systems and genetic regulatory networks (GRNs) that model how genes influence each other in cell-level development of organisms. The inference for GRNs provides important insights into the fundamental biological processes such as growth and is useful in disease diagnosis and genomic drug design. Due to the experimental design, multilevel data hierarchies are often present in time-course gene expression data. Most existing methods, however, ignore the dependency of the expression measurements over time and the correlation among gene expression profiles. Such independence assumptions violate regulatory interactions and can result in overlooking certain important subject effects and lead to spurious inference for regulatory networks or mechanisms. In this paper, a multilevel mixed-effects model is adopted to incorporate data hierarchies in the analysis of time-course data, where temporal and subject effects are both assumed to be random. The method starts with the clustering of genes by fitting the mixture model within the multilevel random-effects model framework using the expectation-maximization (EM) algorithm. The network of regulatory interactions is then determined by searching for regulatory control elements (activators and inhibitors) shared by the clusters of co-expressed genes, based on a time-lagged correlation coefficients measurement. The method is applied to two real time-course datasets from the budding yeast (Saccharomyces cerevisiae) genome. It is shown that the proposed method provides clusters of cell-cycle regulated genes that are supported by existing gene function annotations, and hence enables inference on regulatory interactions for the genetic network.

Using generative models for handwritten digit recognition

We describe a method of recognizing handwritten digits by fitting generative models that are built from deformable B-splines with Gaussian ``ink generators'' spaced along the length of the spline. The splines are adjusted using a novel elastic matching procedure based on the Expectation Maximization (EM) algorithm that maximizes the likelihood of the model generating the data. This approach has many advantages. (1) After identifying the model most likely to have generated the data, the system not only produces a classification of the digit but also a rich description of the instantiation parameters which can yield information such as the writing style. (2) During the process of explaining the image, generative models can perform recognition driven segmentation. (3) The method involves a relatively small number of parameters and hence training is relatively easy and fast. (4) Unlike many other recognition schemes it does not rely on some form of pre-normalization of input images, but can handle arbitrary scalings, translations and a limited degree of image rotation. We have demonstrated our method of fitting models to images does not get trapped in poor local minima. The main disadvantage of the method is it requires much more computation than more standard OCR techniques.

Robust control of nonlinear stochastic systems by modelling conditional distributions of control signals

We introduce a novel inversion-based neuro-controller for solving control problems involving uncertain nonlinear systems that could also compensate for multi-valued systems. The approach uses recent developments in neural networks, especially in the context of modelling statistical distributions, which are applied to forward and inverse plant models. Provided that certain conditions are met, an estimate of the intrinsic uncertainty for the outputs of neural networks can be obtained using the statistical properties of networks. More generally, multicomponent distributions can be modelled by the mixture density network. In this work a novel robust inverse control approach is obtained based on importance sampling from these distributions. This importance sampling provides a structured and principled approach to constrain the complexity of the search space for the ideal control law. The performance of the new algorithm is illustrated through simulations with example systems.

Conditional distribution modeling for estimating and exploiting uncertainty in control systems

This paper presents a general methodology for estimating and incorporating uncertainty in the controller and forward models for noisy nonlinear control problems. Conditional distribution modeling in a neural network context is used to estimate uncertainty around the prediction of neural network outputs. The developed methodology circumvents the dynamic programming problem by using the predicted neural network uncertainty to localize the possible control solutions to consider. A nonlinear multivariable system with different delays between the input-output pairs is used to demonstrate the successful application of the developed control algorithm. The proposed method is suitable for redundant control systems and allows us to model strongly non Gaussian distributions of control signal as well as processes with hysteresis.

Quantifying simulator discrepancy in discrete-time dynamical simulators

When making predictions with complex simulators it can be important to quantify the various sources of uncertainty. Errors in the structural specification of the simulator, for example due to missing processes or incorrect mathematical specification, can be a major source of uncertainty, but are often ignored. We introduce a methodology for inferring the discrepancy between the simulator and the system in discrete-time dynamical simulators. We assume a structural form for the discrepancy function, and show how to infer the maximum-likelihood parameter estimates using a particle filter embedded within a Monte Carlo expectation maximization (MCEM) algorithm. We illustrate the method on a conceptual rainfall-runoff simulator (logSPM) used to model the Abercrombie catchment in Australia. We assess the simulator and discrepancy model on the basis of their predictive performance using proper scoring rules. This article has supplementary material online. © 2011 International Biometric Society.

Novel visualization methods for protein data

Visualization of high-dimensional data has always been a challenging task. Here we discuss and propose variants of non-linear data projection methods (Generative Topographic Mapping (GTM) and GTM with simultaneous feature saliency (GTM-FS)) that are adapted to be effective on very high-dimensional data. The adaptations use log space values at certain steps of the Expectation Maximization (EM) algorithm and during the visualization process. We have tested the proposed algorithms by visualizing electrostatic potential data for Major Histocompatibility Complex (MHC) class-I proteins. The experiments show that the variation in the original version of GTM and GTM-FS worked successfully with data of more than 2000 dimensions and we compare the results with other linear/nonlinear projection methods: Principal Component Analysis (PCA), Neuroscale (NSC) and Gaussian Process Latent Variable Model (GPLVM).

Network lifetime maximization with cross-layer design in wireless sensor networks

This paper investigates a cross-layer design approach for minimizing energy consumption and maximizing network lifetime (NL) of a multiple-source and single-sink (MSSS) WSN with energy constraints. The optimization problem for MSSS WSN can be formulated as a mixed integer convex optimization problem with the adoption of time division multiple access (TDMA) in medium access control (MAC) layer, and it becomes a convex problem by relaxing the integer constraint on time slots. Impacts of data rate, link access and routing are jointly taken into account in the optimization problem formulation. Both linear and planar network topologies are considered for NL maximization (NLM). With linear MSSS and planar single-source and single-sink (SSSS) topologies, we successfully use Karush-Kuhn-Tucker (KKT) optimality conditions to derive analytical expressions of the optimal NL when all nodes are exhausted simultaneously. The problem for planar MSSS topology is more complicated, and a decomposition and combination (D&C) approach is proposed to compute suboptimal solutions. An analytical expression of the suboptimal NL is derived for a small scale planar network. To deal with larger scale planar network, an iterative algorithm is proposed for the D&C approach. Numerical results show that the upper-bounds of the network lifetime obtained by our proposed optimization models are tight. Important insights into the NL and benefits of cross-layer design for WSN NLM are obtained.

Gaussian process quantile regression using expectation propagation

Direct quantile regression involves estimating a given quantile of a response variable as a function of input variables. We present a new framework for direct quantile regression where a Gaussian process model is learned, minimising the expected tilted loss function. The integration required in learning is not analytically tractable so to speed up the learning we employ the Expectation Propagation algorithm. We describe how this work relates to other quantile regression methods and apply the method on both synthetic and real data sets. The method is shown to be competitive with state of the art methods whilst allowing for the leverage of the full Gaussian process probabilistic framework.

Monte Carlo Algorithm for Solving Integral Equations with Polynomial Non-Linearity. Parallel Implementation

An iterative Monte Carlo algorithm for evaluating linear functionals of the solution of integral equations with polynomial non-linearity is proposed and studied. The method uses a simulation of branching stochastic processes. It is proved that the mathematical expectation of the introduced random variable is equal to a linear functional of the solution. The algorithm uses the so-called almost optimal density function. Numerical examples are considered. Parallel implementation of the algorithm is also realized using the package ATHAPASCAN as an environment for parallel realization.The computational results demonstrate high parallel efficiency of the presented algorithm and give a good solution when almost optimal density function is used as a transition density.

Em Estimation of the Offspring Distribution in Mutitype Branching Processes - a Model in Cell Kinetics

2000 Mathematics Subject Classification: 60J80, 60J85, 62P10, 92D25.