21,998 research outputs found
Variational approximation for mixtures of linear mixed models
Mixtures of linear mixed models (MLMMs) are useful for clustering grouped
data and can be estimated by likelihood maximization through the EM algorithm.
The conventional approach to determining a suitable number of components is to
compare different mixture models using penalized log-likelihood criteria such
as BIC.We propose fitting MLMMs with variational methods which can perform
parameter estimation and model selection simultaneously. A variational
approximation is described where the variational lower bound and parameter
updates are in closed form, allowing fast evaluation. A new variational greedy
algorithm is developed for model selection and learning of the mixture
components. This approach allows an automatic initialization of the algorithm
and returns a plausible number of mixture components automatically. In cases of
weak identifiability of certain model parameters, we use hierarchical centering
to reparametrize the model and show empirically that there is a gain in
efficiency by variational algorithms similar to that in MCMC algorithms.
Related to this, we prove that the approximate rate of convergence of
variational algorithms by Gaussian approximation is equal to that of the
corresponding Gibbs sampler which suggests that reparametrizations can lead to
improved convergence in variational algorithms as well.Comment: 36 pages, 5 figures, 2 tables, submitted to JCG
Mixtures of Regression Models for Time-Course Gene Expression Data: Evaluation of Initialization and Random Effects
Finite mixture models are routinely applied to time course microarray data.
Due to the complexity and size of this type of data the choice of good starting values plays
an important role. So far initialization strategies have only been investigated for data
from a mixture of multivariate normal distributions. In this work several initialization
procedures are evaluated for mixtures of regression models with and without random
effects in an extensive simulation study on different artificial datasets. Finally these
procedures are also applied to a real dataset from E. coli
Partial mixture model for tight clustering of gene expression time-course
Background: Tight clustering arose recently from a desire to obtain tighter and potentially more informative clusters in gene expression studies. Scattered genes with relatively loose correlations should be excluded from the clusters. However, in the literature there is little work dedicated to
this area of research. On the other hand, there has been extensive use of maximum likelihood techniques for model parameter estimation. By contrast, the minimum distance estimator has been largely ignored.
Results: In this paper we show the inherent robustness of the minimum distance estimator that makes it a powerful tool for parameter estimation in model-based time-course clustering. To apply minimum distance estimation, a partial mixture model that can naturally incorporate replicate
information and allow scattered genes is formulated. We provide experimental results of simulated data fitting, where the minimum distance estimator demonstrates superior performance to the maximum likelihood estimator. Both biological and statistical validations are conducted on a
simulated dataset and two real gene expression datasets. Our proposed partial regression clustering algorithm scores top in Gene Ontology driven evaluation, in comparison with four other popular clustering algorithms.
Conclusion: For the first time partial mixture model is successfully extended to time-course data analysis. The robustness of our partial regression clustering algorithm proves the suitability of the ombination of both partial mixture model and minimum distance estimator in this field. We show that tight clustering not only is capable to generate more profound understanding of the dataset
under study well in accordance to established biological knowledge, but also presents interesting new hypotheses during interpretation of clustering results. In particular, we provide biological evidences that scattered genes can be relevant and are interesting subjects for study, in contrast to prevailing opinion
Bayesian correlated clustering to integrate multiple datasets
Motivation: The integration of multiple datasets remains a key challenge in systems biology and genomic medicine. Modern high-throughput technologies generate a broad array of different data types, providing distinct – but often complementary – information. We present a Bayesian method for the unsupervised integrative modelling of multiple datasets, which we refer to as MDI (Multiple Dataset Integration). MDI can integrate information from a wide range of different datasets and data types simultaneously (including the ability to model time series data explicitly using Gaussian processes). Each dataset is modelled using a Dirichlet-multinomial allocation (DMA) mixture model, with dependencies between these models captured via parameters that describe the agreement among the datasets.
Results: Using a set of 6 artificially constructed time series datasets, we show that MDI is able to integrate a significant number of datasets simultaneously, and that it successfully captures the underlying structural similarity between the datasets. We also analyse a variety of real S. cerevisiae datasets. In the 2-dataset case, we show that MDI’s performance is comparable to the present state of the art. We then move beyond the capabilities of current approaches and integrate gene expression, ChIP-chip and protein-protein interaction data, to identify a set of protein complexes for which genes are co-regulated during the cell cycle. Comparisons to other unsupervised data integration techniques – as well as to non-integrative approaches – demonstrate that MDI is very competitive, while also providing information that would be difficult or impossible to extract using other methods
Network inference and community detection, based on covariance matrices, correlations and test statistics from arbitrary distributions
In this paper we propose methodology for inference of binary-valued adjacency
matrices from various measures of the strength of association between pairs of
network nodes, or more generally pairs of variables. This strength of
association can be quantified by sample covariance and correlation matrices,
and more generally by test-statistics and hypothesis test p-values from
arbitrary distributions. Community detection methods such as block modelling
typically require binary-valued adjacency matrices as a starting point. Hence,
a main motivation for the methodology we propose is to obtain binary-valued
adjacency matrices from such pairwise measures of strength of association
between variables. The proposed methodology is applicable to large
high-dimensional data-sets and is based on computationally efficient
algorithms. We illustrate its utility in a range of contexts and data-sets
A semi-parametric approach to estimate risk functions associated with multi-dimensional exposure profiles: application to smoking and lung cancer
A common characteristic of environmental epidemiology is the multi-dimensional aspect of exposure patterns, frequently reduced to a cumulative exposure for simplicity of analysis. By adopting a flexible Bayesian clustering approach, we explore the risk function linking exposure history to disease. This approach is applied here to study the relationship between different smoking characteristics and lung cancer in the framework of a population based case control study
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