SEARCH · PubMed Health

Results for “EM algorithm”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 703 records · Page 39Linked to original sources

PubMed2001

Using frailties in the accelerated failure time model.

The accelerated failure time (AFT) model is an important alternative to the Cox proportional hazards model (PHM) in survival analysis. For multivariate failure time data we propose to use frailties to explicitly account for possible correlations (and heterogeneity) among failure times. An EM-like algorithm analogous to that in the frailty model for the Cox model is adapted. Through simulation it is shown that its performance compares favorably with that of the marginal independence approach. For illustration we reanalyze a real data set.

Algorithms↗

PubMed2000

Discrete duration models combining dynamic and random effects.

Survival data may include two different sources of variation, namely variation over time and variation over units. If both of these variations are present, neglecting one of them can cause serious bias in the estimations. Here we present an approach for discrete duration data that includes both time-varying and unit-specific effects to model these two variations simultaneously. The approach is a combination of a dynamic survival model with dynamic time-varying baseline and covariate effects and a frailty model measuring unobserved heterogeneity with random effects varying independently over units. Estimation is based on posterior modes, i.e., we maximize the joint posterior distribution of the unknown parameters to avoid numerical integration and simulation techniques, that are necessary in a full Bayesian analysis. Estimation of unknown hyperparameters is achieved by an EM-type algorithm. Finally, the proposed method is applied to data of the Veteran's Administration Lung Cancer Trial.

Algorithms↗

PubMed2005

Estimation of allele frequencies in polyploids under certain patterns of inheritance.

Allele frequencies have long been studied by biologists interested in evolution and speciation. More recently, with the application of molecular markers in human DNA profiling we have also seen the need for reliable population allele frequency estimates for making probabilistic inferences. There is now interest in applying the same DNA profiling technology to identification of plant varieties. HortResearch maintains a large germplasm of horticultural plant species. It is becoming evident that accurate identification of these accessions through DNA fingerprinting is essential for effective utilisation and maintenance of this germplasm. Microsatellites are the markers of choice for this fingerprinting. However, such markers do not reveal the dosage of alleles in a polyploid. Polyploidy is common amongst horticultural plants. Estimating allele frequencies in a polyploid population is, therefore, complicated because of some marker genotypes being phenotypically indistinguishable. For example, in a tetraploid, with four alleles at a locus showing polysomic inheritance, although 35 genotypes are possible, these will fall into only 15 marker phenotypic classes. Furthermore 'null' individuals are rarely detected in polyploids. Furthermore, some polyploids can be cryptic exhibiting disomy, instead of the polysomic inheritance. We will discuss the implications of these factors and present an EM-type algorithm for estimating allele frequencies of a polyploid population under certain patterns of inheritance. The method will be demonstrated on simulated data. We also discuss the nature of some of the additional problems that may be encountered with estimating allele frequencies in polyploids for which other solutions still need to be developed.

Algorithms↗

PubMed2003

FDTD analysis of dielectric-loaded longitudinally slotted rectangular waveguides.

A versatile electromagnetic (EM) computational algorithm, based on the Finite-Difference Time-Domain (FDTD) technique, is developed to analyze longitudinally oriented, square-ended, single slot fixtures and slot-pair configurations cut in the broad wall of a WR-975 guide operating at a frequency of 915 MHz. The finite conductivity of the waveguide walls is accounted for by employing a time-domain Surface-Impedance Boundary Conditions (SIBC) formulation. The proposed FDTD algorithm has been validated against measurements performed on a probe-excited slot cut along the center line of the broad wall of a WR-284 guide and available experimental data for energy coupled from a longitudinal slot pair in the broad wall of a WR-340 guide. Numerical results are-presented to exploit the influence of the constitutive parameters of the processed material as well as protective insulating window slabs mounted on the exterior surface of the slots. Particular attention is given to the resonant length, scattering parameters, and the electric field distribution within lossy objects placed in the near-field region over a range of slot offsets and workloads with extensive results being reported for the first time. It is shown that the FDTD technique can accurately predict the coupling and power absorption characteristics in loads located in the near field zone of the slotted waveguide structures and, therefore, should prove to be a powerful design tool applicable to a wide class of slotted waveguide applicators that may be difficult to analyze using other available techniques.

Computer Simulation↗

PubMed2004

3D RBI-EM reconstruction with spherically-symmetric basis function for SPECT rotating slat collimator.

A single photon emission computed tomography (SPECT) rotating slat collimator with strip detector acquires distance-weighted plane integral data, along with the attenuation factor and distance-dependent detector response. In order to image a 3D object, the slat collimator device has first to spin around its axis and then rotate around the object to produce 3D projection measurements. Compared to the slice-by-slice 2D reconstruction for the parallel-hole collimator and line integral data, a more complex 3D reconstruction is needed for the slat collimator and plane integral data. In this paper, we propose a 3D RBI-EM reconstruction algorithm with spherically-symmetric basis function, also called 'blobs', for the slat collimator. It has a closed and spherically symmetric analytical expression for the 3D Radon transform, which makes it easier to compute the plane integral than the voxel. It is completely localized in the spatial domain and nearly band-limited in the frequency domain. Its size and shape can be controlled by several parameters to have desired reconstructed image quality. A mathematical lesion phantom study has demonstrated that the blob reconstruction can achieve better contrast-noise trade-offs than the voxel reconstruction without greatly degrading the image resolution. A real lesion phantom study further confirmed this and showed that a slat collimator with CZT detector has better image quality than the conventional parallel-hole collimator with NaI detector. The improvement might be due to both the slat collimation and the better energy resolution of the CZT detector.

Algorithms↗

PubMedDate not supplied

Learning multiple evolutionary pathways from cross-sectional data.

We introduce a mixture model of trees to describe evolutionary processes that are characterized by the ordered accumulation of permanent genetic changes. The basic building block of the model is a directed weighted tree that generates a probability distribution on the set of all patterns of genetic events. We present an EM-like algorithm for learning a mixture model of K trees and show how to determine K with a maximum likelihood approach. As a case study, we consider the accumulation of mutations in the HIV-1 reverse transcriptase that are associated with drug resistance. The fitted model is statistically validated as a density estimator, and the stability of the model topology is analyzed. We obtain a generative probabilistic model for the development of drug resistance in HIV that agrees with biological knowledge. Further applications and extensions of the model are discussed.

Algorithms↗

PubMed2006

Flexible empirical Bayes models for differential gene expression.

MOTIVATION: Inference about differential expression is a typical objective when analyzing gene expression data. Recently, Bayesian hierarchical models have become increasingly popular for this type of problem. The two most common hierarchical models are the hierarchical Gamma-Gamma (GG) and Lognormal-Normal (LNN) models. However, to facilitate inference, some unrealistic assumptions have been made. One such assumption is that of a common coefficient of variation across genes, which can adversely affect the resulting inference. RESULTS: In this paper, we extend both the GG and LNN modeling frameworks to allow for gene-specific variances and propose EM based algorithms for parameter estimation. The proposed methodology is evaluated on three experimental datasets: one cDNA microarray experiment and two Affymetrix spike-in experiments. The two extended models significantly reduce the false positive rate while keeping a high sensitivity when compared to the originals. Finally, using a simulation study we show that the new frameworks are also more robust to model misspecification. AVAILABILITY: The R code for implementing the proposed methodology can be downloaded at http://www.stat.ubc.ca/~c.lo/FEBarrays. SUPPLEMENTARY INFORMATION: The supplementary material is available at http://www.stat.ubc.ca/~c.lo/FEBarrays/supp.pdf.

Algorithms↗

PubMed2004

Detecting differential gene expression with a semiparametric hierarchical mixture method.

Mixture modeling provides an effective approach to the differential expression problem in microarray data analysis. Methods based on fully parametric mixture models are available, but lack of fit in some examples indicates that more flexible models may be beneficial. Existing, more flexible, mixture models work at the level of one-dimensional gene-specific summary statistics, and so when there are relatively few measurements per gene these methods may not provide sensitive detectors of differential expression. We propose a hierarchical mixture model to provide methodology that is both sensitive in detecting differential expression and sufficiently flexible to account for the complex variability of normalized microarray data. EM-based algorithms are used to fit both parametric and semiparametric versions of the model. We restrict attention to the two-sample comparison problem; an experiment involving Affymetrix microarrays and yeast translation provides the motivating case study. Gene-specific posterior probabilities of differential expression form the basis of statistical inference; they define short gene lists and false discovery rates. Compared to several competing methodologies, the proposed methodology exhibits good operating characteristics in a simulation study, on the analysis of spike-in data, and in a cross-validation calculation.

Algorithms↗

PubMed2003

Nonparametric disequilibrium mapping of functional sites using haplotypes of multiple tightly linked single-nucleotide polymorphism markers.

As the speed and efficiency of genotyping single-nucleotide polymorphisms (SNPs) increase, using the SNP map, it becomes possible to evaluate the extent to which a common haplotype contributes to the risk of disease. In this study we propose a new procedure for mapping functional sites or regions of a candidate gene of interest using multiple linked SNPs. Based on a case-parent trio family design, we use expectation-maximization (EM) algorithm-derived haplotype frequency estimates of multiple tightly linked SNPs from both unambiguous and ambiguous families to construct a contingency statistic S for linkage disequilibrium (LD) analysis. In the procedure, a moving-window scan for functional SNP sites or regions can cover an unlimited number of loci except for the limitation of computer storage. Within a window, all possible widths of haplotypes are utilized to find the maximum statistic S* for each site (or locus). Furthermore, this method can be applied to regional or genome-wide scanning for determining linkage disequilibrium using SNPs. The sensitivity of the proposed procedure was examined on the simulated data set from the Genetic Analysis Workshop (GAW) 12. Compared with the conventional and generalized TDT methods, our procedure is more flexible and powerful.

Algorithms↗

PubMed1997

Implementation of a model-based nonuniform scatter correction scheme for SPECT.

In this paper four scatter-compensation schemes are considered. The four schemes are all based on a previously developed two-dimensional (2-D) scatter model. Reconstruction is achieved using the iterative expectation-maximization maximum-likelihood (EM-ML) algorithm. The schemes consist of: 1) including the model in both the forward and back projector; 2) just including the model in the forward projector; 3) and 4) implementing the model in a subtraction and addition scheme, respectively. Monte Carlo simulated projection data are used to test the accuracy, convergence properties, and noise properties of the four scatter-compensation schemes. Data are simulated for both uniformly and nonuniformly attenuating objects. The results show that all four correction schemes yield images which are similar in terms of accuracy to that obtained from reconstructing scatter-free data. The subtraction scheme is shown to converge faster than the other compensation schemes, both in terms of iterations and actual time required for reconstruction. The scheme in which the model is only used in the forward-projector and the scatter-addition scheme both performs slightly better, in terms of signal-to-noise ratio (SNR), than the subtraction scheme. However, the forward projector scheme requires significantly more CPU time for reconstruction. The correction scheme in which the scatter model was included in both the forward and backprojectors is shown to produce accurate images with SNR's higher than even a perfect scatter rejection scheme. While the scatter correction scheme with the model in both the forward projector and backprojector has superior noise properties to the other algorithms, the results suggest that the faster subtraction/addition schemes will probably prove most useful for routine clinical scatter compensation.

Image Processing, Computer-Assisted↗

PubMed2001

Augmented inverse probability weighted estimator for Cox missing covariate regression.

This article investigates an augmented inverse selection probability weighted estimator for Cox regression parameter estimation when covariate variables are incomplete. This estimator extends the Horvitz and Thompson (1952, Journal of the American Statistical Association 47, 663-685) weighted estimator. This estimator is doubly robust because it is consistent as long as either the selection probability model or the joint distribution of covariates is correctly specified. The augmentation term of the estimating equation depends on the baseline cumulative hazard and on a conditional distribution that can be implemented by using an EM-type algorithm. This method is compared with some previously proposed estimators via simulation studies. The method is applied to a real example.

Analysis of Variance↗

PubMed2002

On estimation and prediction for spatial generalized linear mixed models.

We use spatial generalized linear mixed models (GLMM) to model non-Gaussian spatial variables that are observed at sampling locations in a continuous area. In many applications, prediction of random effects in a spatial GLMM is of great practical interest. We show that the minimum mean-squared error (MMSE) prediction can be done in a linear fashion in spatial GLMMs analogous to linear kriging. We develop a Monte Carlo version of the EM gradient algorithm for maximum likelihood estimation of model parameters. A by-product of this approach is that it also produces the MMSE estimates for the realized random effects at the sampled sites. This method is illustrated through a simulation study and is also applied to a real data set on plant root diseases to obtain a map of disease severity that can facilitate the practice of precision agriculture.

Algorithms↗

PubMed2006

Interval mapping of quantitative trait loci for time-to-event data with the proportional hazards mixture cure model.

Interval mapping using normal mixture models has been an important tool for analyzing quantitative traits in experimental organisms. When the primary phenotype is time-to-event, it is natural to use survival models such as Cox's proportional hazards model instead of normal mixtures to model the phenotype distribution. An extra challenge for modeling time-to-event data is that the underlying population may consist of susceptible and nonsusceptible subjects. In this article, we propose a semiparametric proportional hazards mixture cure model which allows missing covariates. We discuss applications to quantitative trait loci (QTL) mapping when the primary trait is time-to-event from a population of mixed susceptibility. This model can be used to characterize QTL effects on both susceptibility and time-to-event distribution, and to estimate QTL location. The model can naturally incorporate covariate effects of other risk factors. Maximum likelihood estimates for the parameters in the model as well as their corresponding variance estimates can be obtained numerically using an EM-type algorithm. The proposed methods are assessed by simulations under practical settings and illustrated using a real data set containing survival times of mice after infection with Listeria monocytogenes. An extension to multiple intervals is also discussed.

Algorithms↗

PubMed2006

A multipinhole small animal SPECT system with submillimeter spatial resolution.

Single photon emission computed tomography (SPECT) is an important technology for molecular imaging studies of small animals. In this arena, there is an increasing demand for high performance imaging systems that offer improved spatial resolution and detection efficiency. We have designed a multipinhole small animal imaging system based on position sensitive avalanche photodiode (PSAPD) detectors with the goal of submillimeter spatial resolution and high detection efficiency, which will allow us to minimize the radiation dose to the animal and to shorten the time needed for the imaging study. Our design will use 8 x 24 mm2 PSAPD detector modules coupled to thallium-doped cesium iodide [CsI(Tl)] scintillators, which can achieve an intrinsic spatial resolution of 0.5 mm at 140 keV. These detectors will be arranged in rings of 24 modules each; the animal is positioned in the center of the 9 stationary detector rings which capture projection data from the animal with a cylindrical tungsten multipinhole collimator. The animal is supported on a bed which can be rocked about the central axis to increase angular sampling of the object. In contrast to conventional SPECT pinhole systems, in our design each pinhole views only a portion of the object. However, the ensemble of projection data from all of the multipinhole detectors provide angular sampling that is sufficient to reconstruct tomographic data from the object. The performance of this multipinhole PSAPD imaging system was simulated using a ray tracing program that models the appropriate point spread functions and then was compared against the performance of a dual-headed pinhole SPECT system. The detection efficiency of both systems was simulated and projection data of a hot rod phantom were generated and reconstructed to assess spatial resolution. Appropriate Poisson noise was added to the data to simulate an acquisition time of 15 min and an activity of 18.5 MBq distributed in the phantom. Both sets of data were reconstructed with an ML-EM reconstruction algorithm. In addition, the imaging performance of both systems was evaluated with a uniformity phantom and a realistic digital mouse phantom. Simulations show that our proposed system produces a spatial resolution of 0.8 mm and an average detection efficiency of 630 cps/MBq. In contrast, simulations of the dual-headed pinhole SPECT system produce a spatial resolution of 1.1 mm and an average detection efficiency of 53 cps/MBq. These results suggest that our novel design will achieve high spatial resolution and will improve the detection efficiency by more than an order of magnitude compared to a dual-headed pinhole SPECT system. We expect that this system can perform SPECT with submillimeter spatial resolution, high throughput, and low radiation dose suitable for in vivo imaging of small animals.

Animals↗

PubMed2005

Interactive effects of common beta2-adrenoceptor haplotypes and age on susceptibility to hypertension and receptor function.

Few studies have examined to what extent genetic variants of the beta2-adrenoceptor (ADRB2) are involved in the development of hypertension with age, although beta2-adrenergic receptor responsiveness declines in older subjects. To investigate this, 10 common single-nucleotide polymorphisms (SNPs) in the promoter and coding regions of the ADRB2 gene were genotyped in an unrelated population consisting of 2 ethnic groups: European American (EA; n=610) and African American (AA; n=420). ADRB2 haplotypes were estimated by expectation maximization (EM) algorithm-based methods. In the general population for EAs and AAs, the variants of the ADRB2 gene, including the individual SNPs and their haplotypes, were not associated with hypertension. However, there was a significant interaction between age and one of the common haplotypes (haplotype 1) in EAs (P=0.01). Haplotype 1 was associated with protection against hypertension in young (< or =50 years of age) but not in old (>50 years of age) EAs (odds ratio, 0.5; 95% confidence interval, 0.27 to 0.91; P=0.02). This age-specific effect was further supported by the observations that young subjects carrying > or =1 copy of haplotype 1 had significantly lower diastolic blood pressure and nearly 2-fold higher ADRB2 binding density than the noncarriers (P<0.05). With aging, their ADRB2 numbers decreased to the level of the noncarriers, along with increased body mass index (7%; P<0.05) and decreased heart rate (7%; P<0.001). Our study suggests that age is an important modifier for the effects of ADRB2 polymorphisms on ADRB2 function and the development of hypertension.

Adult↗

PubMed2005

The impact of using related individuals for haplotype reconstruction in population studies.

Recent studies have highlighted the dangers of using haplotypes reconstructed directly from population data for a fine-scale mapping analysis. Family data may help resolve ambiguity, yet can be costly to obtain. This study is concerned with the following question: How much family data (if any) should be used to facilitate haplotype reconstruction in a population study? We conduct a simulation study to evaluate how changes in family information can affect the accuracy of haplotype frequency estimates and phase reconstruction. To reconstruct haplotypes, we introduce an EM-based algorithm that can efficiently accommodate unrelated individuals, parent-child trios, and arbitrarily large half-sib pedigrees. Simulations are conducted for a diverse set of haplotype frequency distributions, all of which have been previously published in empirical studies. A wide variety of important results regarding the effectiveness of using pedigree data in a population study are presented in a coherent, unified framework. Insight into the different properties of the haplotype frequency distribution that can influence experimental design is provided. We show that a preliminary estimate of the haplotype frequency distribution can be valuable in large population studies with fixed resources.

Algorithms↗

PubMed1993

Restricted maximum likelihood estimation of variance components from field data for number of pigs born alive.

Variance components for number of pigs born alive (NBA) were estimated from sow productivity field records collected by purebred breed associations. Data sets analyzed were as follows: Hampshire (n = 13,537), Landrace (n = 10,822), and Spotted (n = 3,949). Variance components for service sire, sire of sow, dam of sow, and residual effects on NBA (adjusted for parity) were estimated. The single-trait model included relationships between service sires, sires of sows, and dams of sows. The model was implemented using an expectation maximization (EM) REML algorithm. A sparse-matrix solver was also used. Heritability estimates for NBA were .13, .13, and .12 for Hampshire, Spotted, and Landrace, respectively. Estimates of maternal genetic (co)variances (m2) expressed as a proportion of the phenotypic variance were .05, .01, and .03 for Hampshire, Spotted, and Landrace, respectively. Results indicated that service sires account for 1 to 2% of the total variation for NBA. Genetic effects influencing NBA seem to be small in these data sets, but selection for increased NBA should be effective.

Analysis of Variance↗

PubMed1994

Genetic correlations in the feed conversion complex of primiparous cows at a recommended and a reduced plane of nutrition.

An experiment at the Agricultural University of Norway provided data to estimate genetic parameters of roughage intake (RI), fat-corrected milk yield (FCM), smoothed BW (SW), weight change (WC), and energy balance (EB). Weekly measurements were averaged in four consecutive 6-wk periods after parturition for each of 331 primiparous Norwegian cows of 20 sires. Amount of concentrate fed was adjusted according to stage of lactation and cows were randomly assigned to a normal or a low level. Animals were given ad libitum access to grass silage. Multiple-trait animal models with all additive genetic relationships incorporated were applied to the subsets of all averages of one trait and all averages in one period. Each model contained for every trait 165 observations, 24 mo-year seasons of calving, and 313 additive genetic effects. (Co)variance components were estimated by an EM-REML algorithm. The heritability of RI increased with negative energy balance from .25 to .86, whereas the estimates were approximately .2 for FCM, .6 to .7 for SW, and .03 to .4 for WC and EB. The correlations between RI and FCM were .37 to .58 phenotypically and -.11 to .88 genetically; between RI and SW they were .57 to .73 phenotypically and .7 to 1 genetically; between FCM and SW they were -.06 to .35 phenotypically and -.33 to .70 genetically; and between WC and EB they were .52 to .92 phenotypically and -.09 to .88 genetically. Correlations between WC and EB and other traits were inconsistent over periods and had very high SE.

Animal Nutritional Physiological Phenomena↗