• Journal of Institute of Control, Robotics and Systems
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• v.10 no.12
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• pp.1189-1195
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• 2004

This paper investigates construction of gene (interaction) networks from gene expression time-series data based on evolutionary computation. To illustrate the proposed approach in a comprehensive way, we first assume an artificial gene network and then compare it with the reconstructed network from the gene expression time-series data generated by the artificial network. Next, we employ real gene expression time-series data (Spellman's yeast data) to construct a gene network by applying the proposed approach. From these experiments, we find that the proposed approach can be used as a useful tool for discovering the structure of a gene network as well as the corresponding relations among genes. The constructed gene network can further provide biologists with information to generate/test new hypotheses and ultimately to unravel the gene functions.

• Molecules and Cells
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• v.42 no.8
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• pp.579-588
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• 2019

Gene set enrichment analysis (GSEA) is a popular tool to identify underlying biological processes in clinical samples using their gene expression phenotypes. GSEA measures the enrichment of annotated gene sets that represent biological processes for differentially expressed genes (DEGs) in clinical samples. GSEA may be suboptimal for functional gene sets; however, because DEGs from the expression dataset may not be functional genes per se but dysregulated genes perturbed by bona fide functional genes. To overcome this shortcoming, we developed network-based GSEA (NGSEA), which measures the enrichment score of functional gene sets using the expression difference of not only individual genes but also their neighbors in the functional network. We found that NGSEA outperformed GSEA in identifying pathway gene sets for matched gene expression phenotypes. We also observed that NGSEA substantially improved the ability to retrieve known anti-cancer drugs from patient-derived gene expression data using drug-target gene sets compared with another method, Connectivity Map. We also repurposed FDA-approved drugs using NGSEA and experimentally validated budesonide as a chemical with anti-cancer effects for colorectal cancer. We, therefore, expect that NGSEA will facilitate both pathway interpretation of gene expression phenotypes and anti-cancer drug repositioning. NGSEA is freely available at www.inetbio.org/ngsea.

• Genomics & Informatics
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• v.21 no.3
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• pp.38.1-38.8
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• 2023

Non-small cell lung cancer (NSCLC) is an important cause of cancer-associated deaths worldwide. Therefore, the exact molecular mechanisms of NSCLC are unidentified. The present investigation aims to identify the miRNAs with predictive value in NSCLC. The two datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DEmiRNA) and mRNAs (DEmRNA) were selected from the normalized data. Next, miRNA-mRNA interactions were determined. Then, co-expression network analysis was completed using the WGCNA package in R software. The co-expression network between DEmiRNAs and DEmRNAs was calculated to prioritize the miRNAs. Next, the enrichment analysis was performed for DEmiRNA and DEmRNA. Finally, the drug-gene interaction network was constructed by importing the gene list to dgidb database. A total of 3,033 differentially expressed genes and 58 DEmiRNA were recognized from two datasets. The co-expression network analysis was utilized to build a gene co- expression network. Next, four modules were selected based on the Z_summary score. In the next step, a bipartite miRNA-gene network was constructed and hub miRNAs (let-7a-2-3p, let-7d-5p, let-7b-5p, let-7a-5p, and let-7b-3p) were selected. Finally, a drug-gene network was constructed while SUNITINIB, MEDROXYPROGESTERONE ACETATE, DOFETILIDE, HALOPERIDOL, and CALCITRIOL drugs were recognized as a beneficial drug in NSCLC. The hub miRNAs and repurposed drugs may act a vital role in NSCLC progression and treatment, respectively; however, these results must validate in further clinical and experimental assessments.

• International Journal of Advanced Culture Technology
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• v.6 no.4
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• pp.275-283
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• 2018

Cancer show distinct pattern of gene expression when it is compared to normal. This difference results malignant characteristic of cancer. Many cancer drugs are targeting this difference so that it can selectively kill cancer cells. One of the recent demand for personalized treating cancer is retrieving normal tissue from a patient so that the gene expression difference between cancer and normal be assessed. However, in most clinical situation it is hard to retrieve normal tissue from a patient. This is because biopsy of normal tissues may cause damage to the organ function or a risk of infection or side effect what a patient to take. Thus, there is a challenge to estimate normal cell's gene expression where cancers are originated from without taking additional biopsy. In this paper, we propose in-silico based prediction of normal cell's gene expression from gene expression data of a tumor sample. We call this challenge as reverting the cancer into normal. We divided this challenge into two parts. The first part is making a generator that is able to fool a pretrained discriminator. Pretrained discriminator is from the training of public data (9,601 cancers, 7,240 normals) which shows 0.997 of accuracy to discriminate if a given gene expression pattern is cancer or normal. Deceiving this pretrained discriminator means our method is capable of generating very normal-like gene expression data. The second part of the challenge is to address whether generated normal is similar to true reverse form of the input cancer data. We used, cycle-consistent adversarial networks to approach our challenges, since this network is capable of translating one domain to the other while maintaining original domain's feature and at the same time adding the new domain's feature. We evaluated that, if we put cancer data into a cycle-consistent adversarial network, it could retain most of the information from the input (cancer) and at the same time change the data into normal. We also evaluated if this generated gene expression of normal tissue would be the biological reverse form of the gene expression of cancer used as an input.

• Genomics & Informatics
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• v.9 no.4
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• pp.173-180
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• 2011

Recent trends in generating multiple, large-scale datasets provide new challenges to manipulating the relationship of different types of components, such as gene expression and drug response data. Integrative analysis of compound response and gene expression datasets generates an opportunity to capture the possible mechanism of compounds by using signature genes on diverse types of cancer cell lines. Here, we integrated datasets of compound response and gene expression profiles on NCI60 cell lines and constructed a network, revealing the relationship for 801 compounds and 341 gene probes. As examples, obtusol, which shows an exclusive sensitivity on a small number of colon cell lines, is related to a set of gene probes that have unique overexpression in colon cell lines. We also found that the SLC7A11 gene, a direct target of miR-26b, might be a key element in understanding the action of many diverse classes of anticancer compounds. We demonstrated that this network might be useful for studying the mechanisms of varied compound response on diverse cancer cell lines.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.77-77
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• 2003

Gene expression in a cell is regulated by mutual activations or repressions between genes. Identifying the gene regulation network will be one of the most important research topics in the post genomic era. We propose a linear dynamic model of gene regulation for the yeast cell cycle. A small gene network consisting of about 40 genes is reconstructed from the analysis of micro-array gene expression data of yeast S. cerevisiae published by P. Spellman et al. We show that the network construction is consistent with the result of the hierarchical cluster analysis.

• Reproductive and Developmental Biology
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• v.37 no.4
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• pp.185-192
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• 2013

Many countries have implemented genetic evaluation for fertility traits in recent years. In particular, reproductive trait is a complex trait and need to require a system-level approach for identifying candidate genes related to the trait. To find the candidate gene associated with reproductive trait, we applied a weighted gene co-expression network analysis from expression value of bovine genes. We identified three co-expressed modules associated with reproductive trait from bovine microarray data. Hub genes (ZP4, FHL2 and EGR4) were determined in each module; they were topologically centered with statistically significant value in the gene co-expression network. We were able to find the highly co-expressed gene pairs with a correlation coefficient. Finally, the crucial functions of co-expressed modules were reported from functional enrichment analysis. We suggest that the network-based approach in livestock may an important method for analyzing the complex effects of candidate genes associated with economic traits like reproduction.

• Proceedings of the KSRS Conference
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• v.2
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• pp.623-626
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• 2006

Group of genes controls the functioning of a cell by complex interactions. These interacting gene groups are called Gene Regulatory Networks (GRNs). Two previous data mining approaches, clustering and classification have been used to analyze gene expression data. While these mining tools are useful for determining membership of genes by homology, they don't identify the regulatory relationships among genes found in the same class of molecular actions. Furthermore, we need to understand the mechanism of how genes relate and how they regulate one another. In order to detect regulatory relationships among genes from time-series Microarray data, we propose a novel approach using frequent pattern mining and chain rule. In this approach, we propose a method for transforming gene expression data to make suitable for frequent pattern mining, and detect gene expression patterns applying FP-growth algorithm. And then, we construct gene regulatory network from frequent gene patterns using chain rule. Finally, we validated our proposed method by showing that our experimental results are consistent with published results.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3145-3149
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• 2014

Gene expression profiling facilitates the understanding of biological characteristics of gliomas. Previous studies mainly used regression/variance analysis without considering various background biological and environmental factors. The aim of this study was to investigate gene expression differences between grade III and IV gliomas through partial least squares (PLS) based analysis. The expression data set was from the Gene Expression Omnibus database. PLS based analysis was performed with the R statistical software. A total of 1,378 differentially expressed genes were identified. Survival analysis identified four pathways, including Prion diseases, colorectal cancer, CAMs, and PI3K-Akt signaling, which may be related with the prognosis of the patients. Network analysis identified two hub genes, ELAVL1 and FN1, which have been reported to be related with glioma previously. Our results provide new understanding of glioma pathogenesis and prognosis with the hope to offer theoretical support for future therapeutic studies.

• Genomics & Informatics
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• v.13 no.3
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• pp.76-80
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• 2015

Type 2 diabetes mellitus is a complex metabolic disorder associated with multiple genetic, developmental and environmental factors. The recent advances in gene expression microarray technologies as well as network-based analysis methodologies provide groundbreaking opportunities to study type 2 diabetes mellitus. In the present study, we used previously published gene expression microarray datasets of human skeletal muscle samples collected from 20 insulin sensitive individuals before and after insulin treatment in order to construct insulin-mediated regulatory network. Based on a motif discovery method implemented by iRegulon, a Cytoscape app, we identified 25 candidate regulons, motifs of which were enriched among the promoters of 478 up-regulated genes and 82 down-regulated genes. We then looked for a hierarchical network of the candidate regulators, in such a way that the conditional combination of their expression changes may explain those of their target genes. Using Genomica, a software tool for regulatory network construction, we obtained a hierarchical network of eight regulons that were used to map insulin downstream signaling network. Taken together, the results illustrate the benefits of combining completely different methods such as motif-based regulatory factor discovery and expression level-based construction of regulatory network of their target genes in understanding insulin induced biological processes and signaling pathways.