• Communications for Statistical Applications and Methods
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• v.12 no.2
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• pp.335-348
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• 2005

The rapid development of microarray technologies enabled the monitoring of expression levels of thousands of genes simultaneously. Recently, the time course gene expression data are often measured to study dynamic biological systems and gene regulatory networks. For the data, biologists are attempting to group genes based on the temporal pattern of their expression levels. We apply the consensus clustering algorithm to a time course gene expression data in order to infer statistically meaningful information from the measurements. We evaluate each of consensus clustering and existing clustering methods with various validation measures. In this paper, we consider hierarchical clustering and Diana of existing methods, and consensus clustering with hierarchical clustering, Diana and mixed hierachical and Diana methods and evaluate their performances on a real micro array data set and two simulated data sets.

• The Korean Journal of Applied Statistics
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• v.18 no.2
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• pp.371-379
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• 2005

In this paper, we propose a pattern consistency index for detecting heterogeneous time series that deviate from the representative pattern of each cluster in clustering time course gene expression data using the Pearson correlation coefficient. We examine its usefulness by applying this index to serum time course gene expression data from microarrays.

• The Korean Journal of Applied Statistics
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• v.33 no.3
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• pp.269-280
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• 2020

Time course gene expression data is a large amount of data observed over time in microarray experiments. This data can also simultaneously identify the level of gene expression. However, the experiment process is complex, resulting in frequent missing values due to various causes. In this paper, we propose a pattern consistency index adaptive nearest neighbors as a method of missing value imputation. This method combines the adaptive nearest neighbors (ANN) method that reflects local characteristics and the pattern consistency index that considers consistent degree for gene expression between observations over time points. We conducted a Monte Carlo simulation study to evaluate the usefulness of proposed the pattern consistency index adaptive nearest neighbors (PANN) method for two yeast time course data.

• The Korean Journal of Applied Statistics
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• v.26 no.3
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• pp.389-399
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• 2013

This article introduces Gaussian process regression and shows its application with time-course microarray gene expression data. Gene screening for yeast cell cycle microarray expression data is accomplished with a ratio of log marginal likelihood that uses Gaussian process regression with a squared exponential covariance kernel function. Gaussian process regression fitting with each gene is done and shown with the nine top ranking genes. With the screened data the Gaussian model-based clustering is done and its silhouette values are calculated for cluster validity.

• The Korean Journal of Applied Statistics
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• v.21 no.2
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• pp.275-290
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• 2008

The size of microarray gene expression data is very big and its observation process is also very complex. Thus missing values are frequently occurred. In this paper we propose the sequential partial least squares(SPLS) regression fitting method to estimate missing values for time course gene expression data that has correlations among observations over time points. The SPLS method is to combine the sequential technique with the partial least squares(PLS) regression fitting method. The usefulness of method proposed is evaluated through some simulation study for three yeast time course data.

• The Korean Journal of Applied Statistics
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• v.20 no.2
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• pp.409-422
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• 2007

Filtering genes that do not appear to contribute to regulation prior to the statistical analysis of time course gene expression data can reduce the dimensions of data and the possibility of misinterpretation due to noise or lack of variation. In this paper, we compare six different functions for filtering genes with flat pattern under the percentile criterion on an observed sample and that on a bootstrap sample. The result of applying to the yeast cell cycle data shows that the variance function is most similar in both samples.

• The Korean Journal of Applied Statistics
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• v.19 no.1
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• pp.13-32
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• 2006

Biologists are attempting to group genes based on the temporal pattern of gene expression levels. So far, a number of methods have been proposed for clustering microarray data. However, the results of clustering depends on the genes selection, therefore the gene selection with significant expression difference is also very important to cluster for microarray data. Thus, this paper present the results of broad comparative studies to time course microarray data by considering methods of gene selection, clustering and cluster validation.

• Molecules and Cells
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• v.26 no.4
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• pp.338-343
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• 2008

An embryonic stem cell is a powerful tool for investigation of early development in vitro. The study of embryonic stem cell mediated neuronal differentiation allows for improved understanding of the mechanisms involved in embryonic neuronal development. We investigated expression profile changes using time course cDNA microarray to identify clues for the signaling network of neuronal differentiation. For the short time course microarray data, pattern analysis based on the quadratic regression method is an effective approach for identification and classification of a variety of expressed genes that have biological relevance. We studied the expression patterns, at each of 5 stages, after neuronal induction at the mRNA level of embryonic stem cells using the quadratic regression method for pattern analysis. As a result, a total of 316 genes (3.1%) including 166 (1.7%) informative genes in 8 possible expression patterns were identified by pattern analysis. Among the selected genes associated with neurological system, all three genes showing linearly increasing pattern over time, and one gene showing decreasing pattern over time, were verified by RT-PCR. Therefore, an increase in gene expression over time, in a linear pattern, may be associated with embryonic development. The genes: Tcfap2c, Ttr, Wnt3a, Btg2 and Foxk1 detected by pattern analysis, and verified by RT-PCR simultaneously, may be candidate markers associated with the development of the nervous system. Our study shows that pattern analysis, using the quadratic regression method, is very useful for investigation of time course cDNA microarray data. The pattern analysis used in this study has biological significance for the study of embryonic stem cells.

• Journal of Trauma and Injury
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• v.21 no.2
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• pp.120-127
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• 2008

Purpose: Many studies on the time course of inducible nitric oxide synthase (iNOS) gene expression have been performed in the LPS (Lipopolysaccharide)-induced endotoxemic model, but there have been few experimental approaches to continuous peritonitis-induced sepsis model. We conducted this study to establish basic data for future sepsis-related research by investigating the time course of iNOS gene expression and the relationship with the production of inflammatory mediators in the early sepsis model induced by cecal ligation and puncture (CLP). Methods: Male Sprague-Dawley rats were operated on by sing the CLP method to induce of peritonitis; and then, they were sacrificed and samples of blood and lung tissues were obtained at various times (1,2,3,6,9 and 12 h after CLP). We observed the expression of iNOS mRNA from lung tissues and measured the synthesis of nitric oxide, $IL-1{\beta}$, and $TNF-{\alpha}$ from the blood. Results: iNOS mRNA began to be expressed at 3 h and was maintained untill 12 h after CLP. The nitric oxide concentration was increased significantly at 6 h, reached its peak level at 9 h, and maintained a plateau untill 12 h after CLP. $TNF-{\alpha}$ began to be detected at 3 h, increased gradually, and decreased steeply from 9 h after CLP. $IL-1{\beta}$ showed its peak level at 6 h after CLP, and tended to decrease without significance. Conclusion: We observed that the iNOS gene was expressed later in peritonitis-induced sepsis than in LPS-induced sepsis. Nitric oxide and key inflammatory mediators were also expressed later in peritonitis-induced sepsis than in LPS-induced sepsis.

• Molecules and Cells
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• v.21 no.1
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• pp.82-88
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• 2006

The global pattern of growth-dependent gene expression in Streptococcus pneumoniae strains was evaluated using a high-density DNA microarray. Total RNAs obtained from an avirulent S. pneumoniae strain R6 and a virulent strain AMC96-6 were used to compare the expression patterns at seven time points (2.5, 3.5, 4.5, 5.5, 6.0, 6.5, and 8.0 h). The expression profile of strain R6 changed between log and stationary growth (the Log-Stat switch). There were clear differences between the growth-dependent gene expression profiles of the virulent and avirulent pneumococcal strains in 367 of 1,112 genes. Transcripts of genes associated with bacterial competence and capsular polysaccharide formation, as well as clpP and cbpA, were higher in the virulent strain. Our data suggest that late log or early stationary phase may be the most virulent phase of S. pneumoniae.