• Title/Summary/Keyword: ontology enrichment

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Gene Expression Profile and Its Interpretation in Squamous Cell Lung Cancer

  • Park, Dong-Yoon;Kim, Jung-Min;Kim, Ja-Eun;Yoo, Chang-Hyuk;Lee, Han-Yong;Song, Ji-Young;Hwang, Sang-Joon;Yoo, Jae-Cheal;Kim, Sung-Han;Park, Jong-Ho;Yoon, Jeong-Ho
    • Molecular & Cellular Toxicology
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    • v.2 no.4
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    • pp.273-278
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    • 2006
  • 95 squamous cell lung carcinoma samples (normal tissue: 40 samples, tumor: 55 samples) were analyzed with 8 K cDNA microarray. 1-way ANOVA test was employed to select differentially expressed genes in tumor with FDR<0.01. Among the selected 1,655 genes, final 212 genes were chosen according to the expression fold change and used for following analysis. The expression of up-regulated 64 genes was verified with Reverse Transcription PCR and 10 genes were identified as candidates for SCC markers. In our opinion, those candidates can be exploited as diagnostic or therapeutic purposes. Gene Ontology (GO) based analysis was performed using those 212 genes, and following categories were revealed as significant biological processes: Immune response (GO: 0006955), antigen processing (GO: 0030333), inflammatory response (GO: 0006954), Cell adhesion (GO: 0007155), and Epidermis differentiation (GO: 0008544). Gene set enrichment analysis (GSEA) also carried out on overall gene expression profile with 522 functional gene sets. Glycolysis, cell cycle, K-ras and amino acid biosynthesis related gene sets were most distinguished. These results are consistent with the known characteristics of SCC and may be interconnected to rapid cell proliferation. However, the unexpected results from ERK activation in squamous cell carcinoma gripped our attention, and further studies are under progress.

Evolution of the Mir-155 Family and Possible Targets in Cancers and the Immune System

  • Xie, Guang-Bing;Liu, Wei-Jia;Pan, Zhi-Jun;Cheng, Tian-Yin;Luo, Chao
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.18
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    • pp.7547-7552
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    • 2014
  • The mir-155 family is not only involved in a diversity of cancers, but also as a regulator of the immune system. However, the evolutionary history of this family is still unclear. The present study indicates that mir-155 evolved independently with lineage-specific gain of miRNAs. In addition, arm switching has occurred in the mir-155 family, and alternative splicing could produce two different lengths of ancestral sequences, implying the alternative splicing can also drive evolution for intragenic miRNAs. Here we screened validated target genes and immunity-related proteins, followed by analyzation of the mir-155 family function by high-throughput methods like the gene ontology (GO) and Kyoto Eneyclopedin of Genes and Genemes (KEGG) pathway enrichment analysis. The high-throughput analysis showed that the CCND1 and EGFR genes were outstanding in being significantly enriched, and the target genes cebpb and VCAM1 and the protein SMAD2 were also vital in mir-155-related immune reponse activities. Therefore, we conclude that the mir-155 family is highly conserved in evolution, and CCND1 and EGFR genes might be potential targets of mir-155 with regard to progress of cancers, while the cebpb and VCAM1 genes and the protein SMAD2 might be key factors in the mir-155 regulated immune activities.

Partial Least Squares Based Gene Expression Analysis in EBV-Positive and EBV-Negative Posttransplant Lymphoproliferative Disorders

  • Wu, Sa;Zhang, Xin;Li, Zhi-Ming;Shi, Yan-Xia;Huang, Jia-Jia;Xia, Yi;Yang, Hang;Jiang, Wen-Qi
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6347-6350
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    • 2013
  • Post-transplant lymphoproliferative disorder (PTLD) is a common complication of therapeutic immunosuppression after organ transplantation. Gene expression profile facilitates the identification of biological difference between Epstein-Barr virus (EBV) positive and negative PTLDs. Previous studies mainly implemented variance/regression analysis without considering unaccounted array specific factors. The aim of this study is to investigate the gene expression difference between EBV positive and negative PTLDs through partial least squares (PLS) based analysis. With a microarray data set from the Gene Expression Omnibus database, we performed PLS based analysis. We acquired 1188 differentially expressed genes. Pathway and Gene Ontology enrichment analysis identified significantly over-representation of dysregulated genes in immune response and cancer related biological processes. Network analysis identified three hub genes with degrees higher than 15, including CREBBP, ATXN1, and PML. Proteins encoded by CREBBP and PML have been reported to be interact with EBV before. Our findings shed light on expression distinction of EBV positive and negative PTLDs with the hope to offer theoretical support for future therapeutic study.

PRaDA : Web-based analyzer for Pathway Relation and Disease Associated SNP (웹 기반 단일염기다형성 연관 패스웨이 분석 도구)

  • Yu, Kijin;Park, Soo Ho;Ryu, Keun Ho
    • Journal of Digital Contents Society
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    • v.19 no.9
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    • pp.1795-1801
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    • 2018
  • Genome-Wide Association Study (GWAS) have been used to identify susceptibility genes for complex human diseases and many recent studies succeed to report common genetic factors for various diseases. Unfortunately, it is hard to understand all biological functions and mechanisms around the complex disease with GWAS only although the number of known associated genes with diseases is increased drastically because GWAS is a single locus based approach while not a gene but numerous factors may affect a disease associated pathways. PRaDA generates a combined report with genes, pathways and Gene Ontology (GO) using single nucleotide polymorphism (SNP) analysis output. The PRaDA reports not only directly associated pathways but also functionally related ones for identifying accumulated effects of low p-value SNPs. Through integrated information including indirect functional effects, user could have insights of overall disease mechanisms and markers.

Identification of Biomarkers for Diagnosis of Gastric Cancer by Bioinformatics

  • Wang, Da-Guang;Chen, Guang;Wen, Xiao-Yu;Wang, Dan;Cheng, Zhi-Hua;Sun, Si-Qiao
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.4
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    • pp.1361-1365
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    • 2015
  • Background: We aimed to discover potential gene biomarkers for gastric cancer (GC) diagnosis. Materials and Methods: Genechips of 10 GC tissues and 10 gastric mucosa (GM, para-carcinoma tissue, normal control) tissues were generated using an exon array of Affymetrix containing 30,000 genes. The differentially expressed genes (DEGs) between GC tissues and normal control were identified by the Limma package and analyzed by hierarchical clustering analysis. Gene ontology (GO) and pathway enrichment analyses were performed for investigating the functions of DEGs. Receiver operating characteristics (ROC) analysis was performed to measure the effects of biomarker candidates for diagnosis of GC. Results: Totals of 896 up-regulated and 60 down-regulated DEGs were identified to be differentially expressed between GC samples and normal control. Hierarchical clustering analysis showed that DEGs were highly differentially expressed and most DEGs were up-regulated. The most significantly enriched GO-BP term was revealed to be mitotic cell cycle and the most significantly enriched pathway was cell cycle. The intersection analysis showed that most significant DEGs were cyclin B1 (CCNB1) and cyclin B2 (CCNB2). The sensitivities and specificities of CCNB1 and CCNB2 were both high (p<0.0001). Areas under the ROC curve for CCNB1 and CCNB2 were both greater than 0.9 (p<0.0001). Conclusions: CCNB1 and CCNB2, which were involved in cell cycle, played significant roles in the progression and development of GC and these genes may be potential biomarkers for diagnosis and prognosis of GC.

Identifying Differentially Expressed Genes and Screening Small Molecule Drugs for Lapatinib-resistance of Breast Cancer by a Bioinformatics Strategy

  • Zhuo, Wen-Lei;Zhang, Liang;Xie, Qi-Chao;Zhu, Bo;Chen, Zheng-Tang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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    • pp.10847-10853
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    • 2015
  • Background: Lapatinib, a dual tyrosine kinase inhibitor that interrupts the epidermal growth factor receptor (EGFR) and HER2/neu pathways, has been indicated to have significant efficacy in treating HER2-positive breast cancer. However, acquired drug resistance has become a very serious clinical problem that hampers the use of this agent. In this study, we aimed to screen small molecule drugs that might reverse lapatinib-resistance of breast cancer by exploring differentially expressed genes (DEGs) via a bioinformatics method. Materials and Methods: We downloaded the gene expression profile of BT474-J4 (acquired lapatinib-resistant) and BT474 (lapatinib-sensitive) cell lines from the Gene Expression Omnibus (GEO) database and selected differentially expressed genes (DEGs) using dChip software. Then, gene ontology and pathway enrichment analyses were performed with the DAVID database. Finally, a connectivity map was utilized for predicting potential chemicals that reverse lapatinib-resistance. Results: A total of 1, 657 DEGs were obtained. These DEGs were enriched in 10 pathways, including cell cycling, regulation of actin cytoskeleton and focal adhesion associate examples. In addition, several small molecules were screened as the potential therapeutic agents capable of overcoming lapatinib-resistance. Conclusions: The results of our analysis provided a novel strategy for investigating the mechanism of lapatinib-resistance and identifying potential small molecule drugs for breast cancer treatment.

Analysis of cross-population differentiation between Thoroughbred and Jeju horses

  • Lee, Wonseok;Park, Kyung-Do;Taye, Mengistie;Lee, Chul;Kim, Heebal;Lee, Hak-Kyo;Shin, Donghyun
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.8
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    • pp.1110-1118
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    • 2018
  • Objective: This study was intended to identify genes positively selected in Thoroughbred horses (THBs) that potentially contribute to their running performances. Methods: The genomes of THB and Jeju horses (JH, Korean native horse) were compared to identify genes positively selected in THB. We performed cross-population extended haplotype homozygosity (XP-EHH) and cross-population composite likelihood ratio test (XP-CLR) statistical methods for our analysis using whole genome resequencing data of 14 THB and 6 JH. Results: We identified 98 (XP-EHH) and 200 (XP-CLR) genes that are under positive selection in THB. Gene enrichment analysis identified 72 gene ontology biological process (GO BP) terms. The genes and GO BP terms explained some of THB's characteristics such as immunity, energy metabolism and eye size and function related to running performances. GO BP terms that play key roles in several cell signaling mechanisms, which affected ocular size and visual functions were identified. GO BP term Eye photoreceptor cell differentiation is among the terms annotated presumed to affect eye size. Conclusion: Our analysis revealed some positively selected candidate genes in THB related to their racing performances. The genes detected are related to the immunity, ocular size and function, and energy metabolism.

Linking Korean Predicates to Knowledge Base Properties (한국어 서술어와 지식베이스 프로퍼티 연결)

  • Won, Yousung;Woo, Jongseong;Kim, Jiseong;Hahm, YoungGyun;Choi, Key-Sun
    • Journal of KIISE
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    • v.42 no.12
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    • pp.1568-1574
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    • 2015
  • Relation extraction plays a role in for the process of transforming a sentence into a form of knowledge base. In this paper, we focus on predicates in a sentence and aim to identify the relevant knowledge base properties required to elucidate the relationship between entities, which enables a computer to understand the meaning of a sentence more clearly. Distant Supervision is a well-known approach for relation extraction, and it performs lexicalization tasks for knowledge base properties by generating a large amount of labeled data automatically. In other words, the predicate in a sentence will be linked or mapped to the possible properties which are defined by some ontologies in the knowledge base. This lexical and ontological linking of information provides us with a way of generating structured information and a basis for enrichment of the knowledge base.

Transcriptome analysis of Panax ginseng response to high light stress

  • Jung, Je Hyeong;Kim, Ho-Youn;Kim, Hyoung Seok;Jung, Sang Hoon
    • Journal of Ginseng Research
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    • v.44 no.2
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    • pp.312-320
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    • 2020
  • Background: Ginseng (Panax ginseng Meyer) is an essential source of pharmaceuticals and functional foods. Ginseng productivity has been compromised by high light (HL) stress, which is one of the major abiotic stresses during the ginseng cultivation period. The genetic improvement for HL tolerance in ginseng could be facilitated by analyzing its genetic and molecular characteristics associated with HL stress. Methods: Genome-wide analysis of gene expression was performed under HL and recovery conditions in 1-year-old Korean ginseng (P. ginseng cv. Chunpoong) using the Illumina HiSeq platform. After de novo assembly of transcripts, we performed expression profiling and identified differentially expressed genes (DEGs). Furthermore, putative functions of identified DEGs were explored using Gene Ontology terms and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis. Results: A total of 438 highly expressed DEGs in response to HL stress were identified and selected from 29,184 representative transcripts. Among the DEGs, 326 and 114 transcripts were upregulated and downregulated, respectively. Based on the functional analysis, most upregulated and a significant number of downregulated transcripts were related to stress responses and cellular metabolic processes, respectively. Conclusion: Transcriptome profiling could be a strategy to comprehensively elucidate the genetic and molecular mechanisms of HL tolerance and susceptibility. This study would provide a foundation for developing breeding and metabolic engineering strategies to improve the environmental stress tolerance of ginseng.

Comparative transcriptome analysis of heat stress responsiveness between two contrasting ginseng cultivars

  • Jayakodi, Murukarthick;Lee, Sang-Choon;Yang, Tae-Jin
    • Journal of Ginseng Research
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    • v.43 no.4
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    • pp.572-579
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    • 2019
  • Background: Panax ginseng has been used in traditional medicine to strengthen the body and mental well-being of humans for thousands of years. Many elite ginseng cultivars have been developed, and ginseng cultivation has become well established during the last century. However, heat stress poses an important threat to the growth and sustainable production of ginseng. Efforts have been made to study the effects of high temperature on ginseng physiology, but knowledge of the molecular responses to heat stress is still limited. Methods: We sequenced the transcriptomes (RNA-Seq) of two ginseng cultivars, Chunpoong (CP) and Yunpoong (YP), which are sensitive and resistant to heat stress, respectively, after 1- and 3-week heat treatments. Differential gene expression and gene ontology enrichment along with profiled chlorophyll contents were performed. Results: CP is more sensitive to heat stress than YP and exhibited a lower chlorophyll content than YP. Moreover, heat stress reduced the chlorophyll content more rapidly in CP than in YP. A total of 329 heat-responsive genes were identified. Intriguingly, genes encoding chlorophyll a/b-binding proteins, WRKY transcription factors, and fatty acid desaturase were predominantly responsive during heat stress and appeared to regulate photosynthesis. In addition, a genome-wide scan of photosynthetic and sugar metabolic genes revealed reduced transcription levels for ribulose 1,5-bisphosphate carboxylase/oxygenase under heat stress, especially in CP, possibly attributable to elevated levels of soluble sugars. Conclusion: Our comprehensive genomic analysis reveals candidate loci/gene targets for breeding and functional studies related to developing high temperature-tolerant ginseng varieties.