• Genomics & Informatics
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• v.1 no.1
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• pp.32-39
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• 2003

We present a latent variable model-based approach to the analysis of gene expression patterns, coupled with topographic clustering. Aspect model, a latent variable model for dyadic data, is applied to extract latent patterns underlying complex variations of gene expression levels. Then a topographic clustering is performed to find coherent groups of genes, based on the extracted latent patterns as well as individual gene expression behaviors. Applied to cell cycle­regulated genes of the yeast Saccharomyces cerevisiae, the proposed method could discover biologically meaningful patterns related with characteristic expression behavior in particular cell cycle phases. In addition, the display of the variation in the composition of these latent patterns on the cluster map provided more facilitated interpretation of the resulting cluster structure. From this, we argue that latent variable models, coupled with topographic clustering, are a promising tool for explorative analysis of gene expression data.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.111-116
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• 2013

Background: Cigarette smoking is the major risk factor for development of lung cancer. Identification of effects of tobacco on airway gene expression may provide insight into the causes. This research aimed to compare gene expression of large airway epithelium cells in normal smokers (n=13) and non-smokers (n=9) in order to find genes which discriminate the two groups and assess cigarette smoking effects on large airway epithelium cells.Materials and Methods: Genes discriminating smokers from non-smokers were identified by applying a neural network clustering method, growing self-organizing maps (GSOM), to microarray data according to class discrimination scores. An index was computed based on differentiation between each mean of gene expression in the two groups. This clustering approach provided the possibility of comparing thousands of genes simultaneously. Results: The applied approach compared the mean of 7,129 genes in smokers and non-smokers simultaneously and classified the genes of large airway epithelium cells which had differently expressed in smokers comparing with non-smokers. Seven genes were identified which had the highest different expression in smokers compared with the non-smokers group: NQO1, H19, ALDH3A1, AKR1C1, ABHD2, GPX2 and ADH7. Most (NQO1, ALDH3A1, AKR1C1, H19 and GPX2) are known to be clinically notable in lung cancer studies. Furthermore, statistical discriminate analysis showed that these genes could classify samples in smokers and non-smokers correctly with 100% accuracy. With the performed GSOM map, other nodes with high average discriminate scores included genes with alterations strongly related to the lung cancer such as AKR1C3, CYP1B1, UCHL1 and AKR1B10. Conclusions: This clustering by comparing expression of thousands of genes at the same time revealed alteration in normal smokers. Most of the identified genes were strongly relevant to lung cancer in the existing literature. The genes may be utilized to identify smokers with increased risk for lung cancer. A large sample study is now recommended to determine relations between the genes ABHD2 and ADH7 and smoking.

• 한국데이터정보과학회:학술대회논문집
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• 2005.10a
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• pp.153-159
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• 2005

Microarray gene expression technology has applications that could refine diagnosis and therapeutic monitoring as well as improve disease prevention through risk assessment and early detection. Especially, microarray expression data can provide important information regarding specific genes related with metastasis through an appropriate analysis. Various methods for clustering analysis microarray data have been introduced so far. We used twostep clustering fot ascertain metastasis related gene through t-test. Through t-test between two groups for two publicly available medulloblastoma microarray data sets, we intended to find significant gene for metastasis. The paper describes the process in detail showing how the process is applied to clustering analysis and t-test for microarray datasets and how the metastasis-associated genes are explorated.

• Molecular & Cellular Toxicology
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• v.3 no.4
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• pp.246-253
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• 2007

Doxorubicin and daunorubicin are excellent chemotherapeutic agents utilized for several types of cancer but the irreversible cardiac damage is the major limitation for its use. The biochemical mechanisms of doxorubicin- and daunorubicin- induced cardiotoxicity remain unclear. There are many reports on toxicity of doxorubicin and doxorubicin in cardiomyocytes, but effects in cardiovascular system by these drugs are almost not reported. In this study, we investigated gene expression profiles in human umbilical vein endothelial cells (HUVECs) to better understand the causes of doxorubicin and doxorubicininduced cardiovascular toxicity and to identify differentially expressed genes (DEGs). Through the clustering analysis of gene expression profiles, we identified 124 up-regulated common genes and 298 down-regulated common genes changed by more than 1.5-fold by all two cardiac toxicants. HUVECs responded to doxorubicin and doxorubicin damage by increasing levels of apoptosis, oxidative stress, EGF and lipid metabolism related genes. By clustering analysis, we identified some genes as potential markers on apoptosis effects of doxorubicin and doxorubicin. Six genes of these, BBC3, APLP1, FAS, TP53INP, BIRC5 and DAPK were the most significantly affected by doxorubicin and doxorubicin. Thus, this study suggests that these differentially expressed genes may play an important role in the cardiovascular toxic effects and have significant potential as novel biomarkers to doxorubicin and doxorubicin exposure.

• Genomics & Informatics
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• v.7 no.2
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• pp.85-96
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• 2009

The differentiation of neural precursor cells (NPCs) into neurons and astrocytes is a process that is tightly controlled by complicated and ill-defined gene networks. To extend our knowledge to gene networks, we performed a temporal analysis of gene expression during the differentiation (2, 4, and 8 days) of spinal cord-derived NPCs using oligonucleotide microarray technology. Out of 32,996 genes analyzed, 1878 exhibited significant changes in expression level (fold change>2, p<0.05) at least once throughout the differentiation process. These 1878 genes were classified into 12 groups by k-means clustering, based on their expression patterns. K-means clustering analysis revealed that the genes involved in astrogenesis were categorized into the clusters containing constantly upregulated genes, whereas the genes involved in neurogenesis were grouped to the cluster showing a sudden decrease in gene expression on Day 8. Functional analysis of the differentially expressed genes indicated the enrichment of genes for Pax6- NeuroD signaling.TGFb-SMAD and BMP-SMAD.which suggest the implication of these genes in the differentiation of NPCs and, in particular, key roles for Nova1 and TGFBR1 in the neurogenesis/astrogenesis of mouse spinal cord.

• The KIPS Transactions:PartD
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• v.17D no.3
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• pp.175-184
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• 2010

Experiments and research on genes have become very convenient by using DNA chips, which provide large amounts of data from various experiments. The data provided by the DNA chips could be represented as a two dimensional matrix, in which one axis represents genes and the other represents samples. By performing an efficient and good quality clustering on such data, the classification work which follows could be more efficient and accurate. In this paper, we use a bio-inspired algorithm called the Particle Swarm Optimization algorithm to propose an efficient clustering mechanism for large amounts of DNA chip data, and show through experimental results that the clustering technique using the PSO algorithm provides a faster yet good quality result compared with other existing clustering solutions.

• Genomics & Informatics
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• v.2 no.1
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• pp.19-29
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• 2004

Gene expression profiles may offer more information than morphology and provide an alternative to morphology- based tumor classification systems. Informative gene selection is finding gene subsets that are able to discriminate between tumor types, and may have clear biological interpretation. Gene selection is a fundamental issue in gene expression based tumor classification. In this report, techniques for selecting informative genes are illustrated and supervised shaving introduced as a gene selection method in the place of a clustering algorithm. The supervised shaving method showed good performance in gene selection and classification, even though it is a clustering algorithm. Almost selected genes are related to leukemia disease. The expression profiles of 3051 genes were analyzed in 27 acute lymphoblastic leukemia and 11 myeloid leukemia samples. Through these examples, the supervised shaving method has been shown to produce biologically significant genes of more than $94\%$ accuracy of classification. In this report, SVM has also been shown to be a practicable method for gene expression-based classification.

• The Korean Journal of Applied Statistics
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• v.33 no.4
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• pp.511-526
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• 2020

Single-cell RNA-sequencing (scRNA-seq) data consists of each cell's RNA expression extracted from large populations of cells. One main purpose of using scRNA-seq data is to identify inter-cellular heterogeneity. However, scRNA-seq data pose statistical challenges when applying traditional clustering methods because they have many missing values and high level of noise due to technical and sampling issues. In this paper, motivated by analyzing scRNA-seq data, we propose a novel spectral-based clustering method by imposing different weights on genes when computing a similarity between cells. Assigning weights on genes and clustering cells are performed simultaneously in the proposed clustering framework. We solve the proposed non-convex optimization using an iterative algorithm. Both real data application and simulation study suggest that the proposed clustering method better identifies underlying clusters compared with existing clustering methods.

• Journal of KIISE:Software and Applications
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• v.31 no.12
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• pp.1591-1601
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• 2004

Clustering, a technique for the analysis of the genes, organizes the patterns into groups by the similarity of the dataset and has been used for identifying the functions of the genes in the cluster or analyzing the functions of unknown gones. Since the genes usually belong to multiple functional families, fuzzy clustering methods are more appropriate than the conventional hard clustering methods which assign a sample to a group. In this paper, a Bayesian validation method is proposed to evaluate the fuzzy partitions effectively. Bayesian validation method is a probability-based approach, selecting a fuzzy partition with the largest posterior probability given the dataset. At first, the proposed Bayesian validation method is compared to the 4 representative conventional fuzzy cluster validity measures in 4 well-known datasets where foray c-means algorithm is used. Then, we have analyzed the results of Saccharomyces cell cycle expression data evaluated by the proposed method.

• Genomics & Informatics
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• v.5 no.3
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• pp.124-128
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• 2007

Microarray technology enables us to measure the expression of tens of thousands of genes simultaneously under various experimental conditions. Clustering analysis is one of the most successful methods for analyzing microarray data using the assumption that co-expressed genes may be co-regulated. It is important to extract meaningful clusters from a long unordered list of clusters and to evaluate the functional homogeneity and heterogeneity of clusters. Many quality measures for clustering results have been suggested in different conditions. In the present study, we consider biological pathways as a collection of biological knowledge and used them as a reference for measuring the quality of clustering results and functional homogeneities. PathTalk visualizes and evaluates functional relationships between gene clusters and biological pathways.