• Title/Summary/Keyword: significant genes

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Possibility of the Use of Public Microarray Database for Identifying Significant Genes Associated with Oral Squamous Cell Carcinoma

  • Kim, Ki-Yeol;Cha, In-Ho
    • Genomics & Informatics
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    • v.10 no.1
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    • pp.23-32
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    • 2012
  • There are lots of studies attempting to identify the expression changes in oral squamous cell carcinoma. Most studies include insufficient samples to apply statistical methods for detecting significant gene sets. This study combined two small microarray datasets from a public database and identified significant genes associated with the progress of oral squamous cell carcinoma. There were different expression scales between the two datasets, even though these datasets were generated under the same platforms - Affymetrix U133A gene chips. We discretized gene expressions of the two datasets by adjusting the differences between the datasets for detecting the more reliable information. From the combination of the two datasets, we detected 51 significant genes that were upregulated in oral squamous cell carcinoma. Most of them were published in previous studies as cancer-related genes. From these selected genes, significant genetic pathways associated with expression changes were identified. By combining several datasets from the public database, sufficient samples can be obtained for detecting reliable information. Most of the selected genes were known as cancer-related genes, including oral squamous cell carcinoma. Several unknown genes can be biologically evaluated in further studies.

Finding significant genes using factor analysis (요인 분석을 이용한 유의한 유전자 추출)

  • Lee, Jeong-Wha;Lee, Hye-Seon;Park, Hae-Sang;Jun, Chi-Hyuck
    • Proceedings of the Korean Operations and Management Science Society Conference
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    • 2006.11a
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    • pp.427-430
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    • 2006
  • Clustering for gene expression data without filtering out noise genes may be distorted or derived inappropriate inference. Identifying significant genes and deleting noise before major analysis is necessary fur meaningful discovery from genes expression pattern. We proposed a new method of finding significant genes using factor analysis which is done on transposed data matrix. We construct significance score that is sum of factor loadings for declared significant number of factor, and set threshold through replication. Our proposed method works well for simulated time-course data for finding significant genes even though variance level gets larger.

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Identifying literature-based significant genes and discovering novel drug indications on PPI network

  • Park, Minseok;Jang, Giup;Lee, Taekeon;Yoon, Youngmi
    • Journal of the Korea Society of Computer and Information
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    • v.22 no.3
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    • pp.131-138
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    • 2017
  • New drug development is time-consuming and costly. Hence, it is necessary to repurpose old drugs for finding new indication. We suggest the way that repurposing old drug using massive literature data and biological network. We supposed a disease-drug relationship can be available if signal pathways of the relationship include significant genes identified in literature data. This research is composed of three steps-identifying significant gene using co-occurrence in literature; analyzing the shortest path on biological network; and scoring a relationship with comparison between the significant genes and the shortest paths. Based on literatures, we identify significant genes based on the co-occurrence frequency between a gene and disease. With the network that include weight as possibility of interaction between genes, we use shortest paths on the network as signal pathways. We perform comparing genes that identified as significant gene and included on signal pathways, calculating the scores and then identifying the candidate drugs. With this processes, we show the drugs having new possibility of drug repurposing and the use of our method as the new method of drug repurposing.

Molecular Biological Study of The Effects of Gilgyung-Tang(GGT) on Cellular Proliferation and Viability of Normal Human Lung Fibriblast Cell (길경탕(桔梗湯)이 인체(人體) 폐세포(肺細胞)에 미치는 영향(影響)에 관(關)한 분자생물학적(分子生物學的) 연구(硏究))

  • Rhee, Hyung-Koo
    • The Journal of Korean Medicine
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    • v.20 no.2
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    • pp.88-97
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    • 1999
  • To characterize the effects of Gilgyung-Tang(GGT) on cellular proliferation and viability of normal lung fibroblast cells, we examined the cell cycle progression and cell cycle-related gene expression in T3891 using a flow cytometry and a quantitative RT-PCR analysis. 1. The significant surpression effect of cellular proliferations of GGT was observed in proportion to a certain concentration and time. 2. GGT was identified to induce apoptotic death of damaged cells by treatment with a DNA-damage agent and etoposide, while it stimulated the recovery of cellular viability of normal cells. 3 The significant reductions of mRNA expression of PCAN, c-Fos treated by GGT were observed. 4. The significant inductions of mRNA expression of p53, CDKN1. Gadd45 treated by GGT were observed. 5. The apoptosis caused by the reduction of Bcl-2 genes was significant and the Bax genes were increased. but the amount of Fas genes were not changed. These results strongly suggest that GGT triggers arrest of the cell cycle at G1 phase, and thus causes an inhibition of cellular proliferation of human normal lung cells through the transcriptional up-regulation of cell cycle inhibitory genes and down-regulation of induction of cell cycle stimulating genes respectably.

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Genomic Insights into the Rice Blast Fungus through Estimation of Gene Emergence Time in Phylogenetic Context

  • Choi, Jaeyoung;Lee, Jong-Joon;Jeon, Junhyun
    • Mycobiology
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    • v.46 no.4
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    • pp.361-369
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    • 2018
  • The rice blast fungus, Magnaporthe oryzae, is an important pathogen of rice plants. It is well known that genes encoded in the genome have different evolutionary histories that are related to their functions. Phylostratigraphy is a method that correlates the evolutionary origin of genes with evolutionary transitions. Here we applied phylostratigraphy to partition total gene content of M. oryzae into distinct classes (phylostrata), which we designated PS1 to PS7, based on estimation of their emergence time. Genes in individual phylostrata did not show significant biases in their global distribution among seven chromosomes, but at the local level, clustering of genes belonging to the same phylostratum was observed. Our phylostrata-wide analysis of genes revealed that genes in the same phylostratum tend to be similar in many physical and functional characteristics such as gene length and structure, GC contents, codon adaptation index, and level of transcription, which correlates with biological functions in evolutionary context. We also found that a significant proportion of genes in the genome are orphans, for which no orthologs can be detected in the database. Among them, we narrowed down to seven orphan genes having transcriptional and translational evidences, and showed that one of them is implicated in asexual reproduction and virulence, suggesting ongoing evolution in this fungus through lineage-specific genes. Our results provide genomic basis for linking functions of pathogenicity factors and gene emergence time.

Genome-Wide Association Studies Associated with Backfat Thickness in Landrace and Yorkshire Pigs

  • Lee, Young-Sup;Shin, Donghyun
    • Genomics & Informatics
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    • v.16 no.3
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    • pp.59-64
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    • 2018
  • Although pork quality traits are important commercially, genome-wide association studies (GWASs) have not well considered Landrace and Yorkshire pigs worldwide. Landrace and Yorkshire pigs are important pork-providing breeds. Although quantitative trait loci of pigs are well-developed, significant genes in GWASs of pigs in Korea must be studied. Through a GWAS using the PLINK program, study of the significant genes in Korean pigs was performed. We conducted a GWAS and surveyed the gene ontology (GO) terms associated with the backfat thickness (BF) trait of these pigs. We included the breed information (Yorkshire and Landrace pigs) as a covariate. The significant genes after false discovery rate (<0.01) correction were AFG1L, SCAI, RIMS1, and SPDEF. The major GO terms for the top 5% of genes were related to neuronal genes, cell morphogenesis and actin cytoskeleton organization. The neuronal genes were previously reported as being associated with backfat thickness. However, the genes in our results were novel, and they included ZNF280D, BAIAP2, LRTM2, GABRA5, PCDH15, HERC1, DTNBP1, SLIT2, TRAPPC9, NGFR, APBB2, RBPJ, and ABL2. These novel genes might have roles in important cellular and physiological functions related to BF accumulation. The genes related to cell morphogenesis were NOX4, MKLN1, ZNF280D, BAIAP2, DNAAF1, LRTM2, PCDH15, NGFR, RBPJ, MYH9, APBB2, DTNBP1, TRIM62, and SLIT2. The genes that belonged to actin cytoskeleton organization were MKLN1, BAIAP2, PCDH15, BCAS3, MYH9, DTNBP1, ABL2, ADD2, and SLIT2.

Integrated bioinformatics analysis of validated and circulating miRNAs in ovarian cancer

  • Dogan, Berkcan;Gumusoglu, Ece;Ulgen, Ege;Sezerman, Osman Ugur;Gunel, Tuba
    • Genomics & Informatics
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    • v.20 no.2
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    • pp.20.1-20.13
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    • 2022
  • Recent studies have focused on the early detection of ovarian cancer (OC) using tumor materials by liquid biopsy. The mechanisms of microRNAs (miRNAs) to impact OC and signaling pathways are still unknown. This study aims to reliably perform functional analysis of previously validated circulating miRNAs' target genes by using pathfindR. Also, overall survival and pathological stage analyses were evaluated with miRNAs' target genes which are common in the The Cancer Genome Atlas and GTEx datasets. Our previous studies have validated three downregulated miRNAs (hsa-miR-885-5p, hsa-miR-1909-5p, and hsa-let7d-3p) having a diagnostic value in OC patients' sera, with high-throughput techniques. The predicted target genes of these miRNAs were retrieved from the miRDB database (v6.0). Active-subnetwork-oriented Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted by pathfindR using the target genes. Enrichment of KEGG pathways assessed by the analysis of pathfindR indicated that 24 pathways were related to the target genes. Ubiquitin-mediated proteolysis, spliceosome and Notch signaling pathway were the top three pathways with the lowest p-values (p < 0.001). Ninety-three common genes were found to be differentially expressed (p < 0.05) in the datasets. No significant genes were found to be significant in the analysis of overall survival analyses, but 24 genes were found to be significant with pathological stages analysis (p < 0.05). The findings of our study provide in-silico evidence that validated circulating miRNAs' target genes and enriched pathways are related to OC and have potential roles in theranostics applications. Further experimental investigations are required to validate our results which will ultimately provide a new perspective for translational applications in OC management.

Paradigm of Time-sequence Development of the Intestine of Suckling Piglets with Microarray

  • Sun, Yunzi;Yu, Bing;Zhang, Keying;Chen, Xijian;Chen, Daiwen
    • Asian-Australasian Journal of Animal Sciences
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    • v.25 no.10
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    • pp.1481-1492
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    • 2012
  • The interaction of the genes involved in intestinal development is the molecular basis of the regulatory mechanisms of intestinal development. The objective of this study was to identify the significant pathways and key genes that regulate intestinal development in Landrace piglets, and elucidate their rules of operation. The differential expression of genes related to intestinal development during suckling time was investigated using a porcine genome array. Time sequence profiles were analyzed for the differentially expressed genes to obtain significant expression profiles. Subsequently, the most significant profiles were assayed using Gene Ontology categories, pathway analysis, network analysis, and analysis of gene co-expression to unveil the main biological processes, the significant pathways, and the effective genes, respectively. In addition, quantitative real-time PCR was carried out to verify the reliability of the results of the analysis of the array. The results showed that more than 8000 differential expression transcripts were identified using microarray technology. Among the 30 significant obtained model profiles, profiles 66 and 13 were the most significant. Analysis of profiles 66 and 13 indicated that they were mainly involved in immunity, metabolism, and cell division or proliferation. Among the most effective genes in these two profiles, CN161469, which is similar to methylcrotonoyl-Coenzyme A carboxylase 2 (beta), and U89949.1, which encodes a folate binding protein, had a crucial influence on the co-expression network.

Identification of genes related to intramuscular fat content of pigs using genome-wide association study

  • Won, Sohyoung;Jung, Jaehoon;Park, Eungwoo;Kim, Heebal
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.2
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    • pp.157-162
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    • 2018
  • Objective: The aim of this study is to identify single nucleotide polymorphisms (SNPs) and genes related to pig IMF and estimate the heritability of intramuscular fat content (IMF). Methods: Genome-wide association study (GWAS) on 704 inbred Berkshires was performed for IMF. To consider the inbreeding among samples, associations of the SNPs with IMF were tested as random effects in a mixed linear model using the genetic relationship matrix by GEMMA. Significant genes were compared with reported pig IMF quantitative trait loci (QTL) regions and functional classification of the identified genes were also performed. Heritability of IMF was estimated by GCTA tool. Results: Total 365 SNPs were found to be significant from a cutoff of p-value <0.01 and the 365 significant SNPs were annotated across 120 genes. Twenty five genes were on pig IMF QTL regions. Bone morphogenetic protein-binding endothelial cell precursor-derived regulator, forkhead box protein O1, ectodysplasin A receptor, ring finger protein 149, cluster of differentiation, tyrosine-protein phosphatase non-receptor type 1, SRY (sex determining region Y)-box 9 (SOX9), MYC proto-oncogene, and macrophage migration inhibitory factor were related to mitogen-activated protein kinase pathway, which regulates the differentiation to adipocytes. These genes and the genes mapped on QTLs could be the candidate genes affecting IMF. Heritability of IMF was estimated as 0.52, which was relatively high, suggesting that a considerable portion of the total variance of IMF is explained by the SNP information. Conclusion: Our results can contribute to breeding pigs with better IMF and therefore, producing pork with better sensory qualities.

Differentially Expressed Genes in Metastatic Advanced Egyptian Bladder Cancer

  • Zekri, Abdel-Rahman N;Hassan, Zeinab Korany;Bahnassy, Abeer A;Khaled, Hussein M;El-Rouby, Mahmoud N;Haggag, Rasha M;Abu-Taleb, Fouad M
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.8
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    • pp.3543-3549
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    • 2015
  • Background: Bladder cancer is one of the most common cancers worldwide. Gene expression profiling using microarray technologies improves the understanding of cancer biology. The aim of this study was to determine the gene expression profile in Egyptian bladder cancer patients. Materials and Methods: Samples from 29 human bladder cancers and adjacent non-neoplastic tissues were analyzed by cDNA microarray, with hierarchical clustering and multidimensional analysis. Results: Five hundred and sixteen genes were differentially expressed of which SOS1, HDAC2, PLXNC1, GTSE1, ULK2, IRS2, ABCA12, TOP3A, HES1, and SRP68 genes were involved in 33 different pathways. The most frequently detected genes were: SOS1 in 20 different pathways; HDAC2 in 5 different pathways; IRS2 in 3 different pathways. There were 388 down-regulated genes. PLCB2 was involved in 11 different pathways, MDM2 in 9 pathways, FZD4 in 5 pathways, p15 and FGF12 in 4 pathways, POLE2 in 3 pathways, and MCM4 and POLR2E in 2 pathways. Thirty genes showed significant differences between transitional cell cancer (TCC) and squamous cell cancer (SCC) samples. Unsupervised cluster analysis of DNA microarray data revealed a clear distinction between low and high grade tumors. In addition 26 genes showed significant differences between low and high tumor stages, including fragile histidine triad, Ras and sialyltransferase 8 (alpha) and 16 showed significant differences between low and high tumor grades, like methionine adenosyl transferase II, beta. Conclusions: The present study identified some genes, that can be used as molecular biomarkers or target genes in Egyptian bladder cancer patients.