25,034 research outputs found
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
SMART: Unique splitting-while-merging framework for gene clustering
Copyright @ 2014 Fa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.Successful clustering algorithms are highly dependent on parameter settings. The clustering performance degrades significantly unless parameters are properly set, and yet, it is difficult to set these parameters a priori. To address this issue, in this paper, we propose a unique splitting-while-merging clustering framework, named “splitting merging awareness tactics” (SMART), which does not require any a priori knowledge of either the number of clusters or even the possible range of this number. Unlike existing self-splitting algorithms, which over-cluster the dataset to a large number of clusters and then merge some similar clusters, our framework has the ability to split and merge clusters automatically during the process and produces the the most reliable clustering results, by intrinsically integrating many clustering techniques and tasks. The SMART framework is implemented with two distinct clustering paradigms in two algorithms: competitive learning and finite mixture model. Nevertheless, within the proposed SMART framework, many other algorithms can be derived for different clustering paradigms. The minimum message length algorithm is integrated into the framework as the clustering selection criterion. The usefulness of the SMART framework and its algorithms is tested in demonstration datasets and simulated gene expression datasets. Moreover, two real microarray gene expression datasets are studied using this approach. Based on the performance of many metrics, all numerical results show that SMART is superior to compared existing self-splitting algorithms and traditional algorithms. Three main properties of the proposed SMART framework are summarized as: (1) needing no parameters dependent on the respective dataset or a priori knowledge about the datasets, (2) extendible to many different applications, (3) offering superior performance compared with counterpart algorithms.National Institute for Health Researc
A nonparametric empirical Bayes framework for large-scale multiple testing
We propose a flexible and identifiable version of the two-groups model,
motivated by hierarchical Bayes considerations, that features an empirical null
and a semiparametric mixture model for the non-null cases. We use a
computationally efficient predictive recursion marginal likelihood procedure to
estimate the model parameters, even the nonparametric mixing distribution. This
leads to a nonparametric empirical Bayes testing procedure, which we call
PRtest, based on thresholding the estimated local false discovery rates.
Simulations and real-data examples demonstrate that, compared to existing
approaches, PRtest's careful handling of the non-null density can give a much
better fit in the tails of the mixture distribution which, in turn, can lead to
more realistic conclusions.Comment: 18 pages, 4 figures, 3 table
Unsupervised Classification for Tiling Arrays: ChIP-chip and Transcriptome
Tiling arrays make possible a large scale exploration of the genome thanks to
probes which cover the whole genome with very high density until 2 000 000
probes. Biological questions usually addressed are either the expression
difference between two conditions or the detection of transcribed regions. In
this work we propose to consider simultaneously both questions as an
unsupervised classification problem by modeling the joint distribution of the
two conditions. In contrast to previous methods, we account for all available
information on the probes as well as biological knowledge like annotation and
spatial dependence between probes. Since probes are not biologically relevant
units we propose a classification rule for non-connected regions covered by
several probes. Applications to transcriptomic and ChIP-chip data of
Arabidopsis thaliana obtained with a NimbleGen tiling array highlight the
importance of a precise modeling and the region classification
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