Integrative Analysis of Microarray Data with Gene Ontology to Select Perturbed Molecular Functions using Gene Ontology Functional Code

김창식,최지원,윤석준 한국유전체학회 2009 Genomics & informatics Vol.7 No.2

A systems biology approach for the identification of perturbed molecular functions is required to understand the complex progressive disease such as breast cancer. In this study, we analyze the microarray data with Gene Ontology terms of molecular functions to select perturbed molecular functional modules in breast cancer tissues based on the definition of Gene ontology Functional Code. The Gene Ontology is three structured vocabularies describing genes and its products in terms of their associated biological processes, cellular components and molecular functions. The Gene Ontology is hierarchically classified as a directed acyclic graph. However, it is difficult to visualize Gene Ontology as a directed tree since a Gene Ontology term may have more than one parent by providing multiple paths from the root. Therefore, we applied the definition of Gene Ontology codes by defining one or more GO code(s) to each GO term to visualize the hierarchical classification of GO terms as a network. The selected molecular functions could be considered as perturbed molecular functional modules that putatively contributes to the progression of disease. We evaluated the method by analyzing microarray dataset of breast cancer tissues; i.e., normal and invasive breast cancer tissues. Based on the integration approach, we selected several interesting perturbed molecular functions that are implicated in the progression of breast cancers. Moreover, these selected molecular functions include several known breast cancer-related genes. It is concluded from this study that the present strategy is capable of selecting perturbed molecular functions that putatively play roles in the progression of diseases and provides an improved interpretability of GO terms based on the definition of Gene Ontology codes.

Integrative Analysis of Microarray Data with Gene Ontology to Select Perturbed Molecular Functions using Gene Ontology Functional Code

Kim, Chang-Sik,Choi, Ji-Won,Yoon, Suk-Joon Korea Genome Organization 2009 Genomics & informatics Vol.7 No.2

A systems biology approach for the identification of perturbed molecular functions is required to understand the complex progressive disease such as breast cancer. In this study, we analyze the microarray data with Gene Ontology terms of molecular functions to select perturbed molecular functional modules in breast cancer tissues based on the definition of Gene ontology Functional Code. The Gene Ontology is three structured vocabularies describing genes and its products in terms of their associated biological processes, cellular components and molecular functions. The Gene Ontology is hierarchically classified as a directed acyclic graph. However, it is difficult to visualize Gene Ontology as a directed tree since a Gene Ontology term may have more than one parent by providing multiple paths from the root. Therefore, we applied the definition of Gene Ontology codes by defining one or more GO code(s) to each GO term to visualize the hierarchical classification of GO terms as a network. The selected molecular functions could be considered as perturbed molecular functional modules that putatively contributes to the progression of disease. We evaluated the method by analyzing microarray dataset of breast cancer tissues; i.e., normal and invasive breast cancer tissues. Based on the integration approach, we selected several interesting perturbed molecular functions that are implicated in the progression of breast cancers. Moreover, these selected molecular functions include several known breast cancer-related genes. It is concluded from this study that the present strategy is capable of selecting perturbed molecular functions that putatively play roles in the progression of diseases and provides an improved interpretability of GO terms based on the definition of Gene Ontology codes.

GO Guide : 생물학 온톨로지를 위한 브라우저 및 질의 변환

정준원(Jun-Won Jung),박형우(Hyoung-Woo Park),임동혁(Dong-Hhyuk Im),이강표(Kang-Pyo Lee),김형주(Hyoung-Joo Kim) 한국정보과학회 2006 정보과학회 컴퓨팅의 실제 논문지 Vol.12 No.3

생물학 분야에서 유전자에 대한 연구가 활발하게 이루어지면서 유전자에 대한 정보 구축 및 통합에 대한 필요성이 대두 되었다. 그 결과 Gene Ontology Consortium은 W3C에서 제정한 온톨로지 기술언어인 OWL로 유전자에 대한 정보와 분류를 담고 있는 Gene Ontology를 구축하였다. 하지만 Gene Ontology를 위한 기존의 브라우저들은 키워드, 트리, 그래프 기반의 단순 검색만을 지원할 뿐 다양한 관계를 고려한 고급 정보 검색이 불가능하다. 본 논문은 실제 생물학 연구를 수행하는 사용자들이 Gene Ontology를 효과적이고 편리하게 사용할 수 있도록 하기 위해 다양한 온톨로지 검색 기법을 통합적으로 지원하는 방법을 제안하였다. 또한 질의어 입력대신 검색 중에 손쉽게 질의를 생성하는 기법과 생성된 질의를 SeRQL 질의로 변환하는 기법을 제안함으로써 온톨로지에서 지원하는 질의어에 독립적으로 손쉽게 질의를 생성하고 고급정보를 얻을 수 있도록 하였다. 그리고 이렇게 구축한 GO Guide 브라우저를 통해 Gene Ontology의 방대한 정보를 효과적으로 이용할 수 있음을 확인하였다. As genetic research is getting more active, data construction of genes are needed in the field of biology. Therefore, Gene Ontology Consortium has constructed genetic information by OWL, which is Ontology description language published by W3C. However, previous browsers for Gene Ontology only support simple searching mechanisms based on keyword, tree, and graph, but it is not able to search high quality information considering various relationships. In this paper, we suggest browsing technique which integratesvarious searching methods to support researchers who are doing actually experiment in biology field. Also, instead of typing a query, we propose query generation technique which constructs query while browsing and query translation technique which translate generated query into SeRQL query. It is convenient for user and enables user to obtain high quality information. And by this GO Guide browser, it has been shown that the information of Gene Ontology could be used efficiently.

Integrated omics analysis of root-preferred genes across diverse rice varieties including Japonica and indica cultivars

Moon, Sunok,Chandran, Anil Kumar Nalini,Gho, Yun-Shil,Park, Sun-A,Kim, Sung-Ryul,Yoo, Yo-Han,Jung, Ki-Hong G. Fischer 2018 Journal of plant physiology Vol. No.

<P>Plant root systems play essential roles in developmental processes, such as the absorption of water and inorganic nutrients, and structural support. Gene expression is affected by growth conditions and the genetic background of plants. To identify highly conserved root-preferred genes in rice across diverse growth conditions and varieties, we used two independent meta-anatomical expression profiles based on a large collection of Affymetrix and Agilent 44 K microarray data sets available for public use. We then identified 684 loci with root-preferred expression, which were validated with in silico analysis using both meta-expression profiles. The expression patterns of four candidate genes were confirmed in vivo by monitoring expression of beta-glucuronidase under control of the candidate-gene promoters, providing new tools to manipulate agronomic traits associated with roots. We also utilized real-time PCR to examine the root-preferential expression of 14 genes across four rice varieties, including japonica and indica cultivars. Using a database of rice genes with known functions, we identified the reported functions of 39 out of the 684 candidate genes. Sixteen genes are directly involved in root development, while the remaining are involved in processes indirectly related to root development (i.e., soil-stress tolerance or growth retardation). This indicates the importance of our candidate genes for studies on root development and function. Gene ontology enrichment analysis in the 'biological processes' category revealed that root-preferred genes in rice are closely associated with nutrient transport-related genes, indicating that the primary role of roots is the uptake of nutrients from soil. In addition, predicted protein-protein interaction analysis suggested a molecular network for root development composed of 215 interactions associated with 44 root-preferred or root development-related genes. Taken together, our data provide an important foundation for future research on root development in rice.</P>

Array2GO: a simple web-based tool to search gene ontology for analysis of multi genes expression

김준섭,김승준,이승용,한정,안유리,김아랑,황승용 한국바이오칩학회 2010 BioChip Journal Vol.4 No.4

As a result of population and universality in high-throughput omics technologies in the last decade, such as microarray methods, many researchers who study their genes of interest that are similarly or differently expressed in cellular states, diseases, functional,or environmental element conditions have been possessed of the ability to identify biological validation on the genomic scale. In parallel with the advancement of omics experiments, the number of biological databases, which contain the biological annotations, genetic functionalities, metabolic pathways, and mutational information or functional interactions between genes or proteins, has increased. Fortunately, these datasets have been mainly opened to computational network protocols, such as FTP or SSH, and have freely served as web search tools to enable users to retrieve a biological annotation with queries. Of these databases, GO (Gene Ontology) provides controlled vocabulary terms for describing biological annotation of a gene or gene product in tree aspects that are classified as biological process, cellular component, and molecular function across various species. Also, GO gives researchers a publicly accessible tool for identification of a gene or gene product with GO terms. The result of this tool displays the hierarchical tree-type html format or DAGs (Directed Acyclic Graphs) graphtype format to users according to the three aspects of GO. However, as this permits users to ask only one keyword at a time, it is difficult to search many interesting gene sets in gene expression profiles obtained from microarray experiments at once. A few GO search tools have been developed to help in analysis of GO annotation for multi genes. However they have not satisfied user demands in terms of the simplicity of the user interface and visualization of analysis results. For these reasons, Array2GO, which has been based on a web environment, has been developed and is freely accessible at http://www.koreagene.co.kr/cgi-bin/service/service1.pl.

영하의 저온에 노출된 ‘Campbell Early’와 ‘Muscat Bailey A’ 포도나무 신초의전사체 비교

김선애,윤해근 한국식물생명공학회 2016 JOURNAL OF PLANT BIOTECHNOLOGY Vol.43 No.2

To understand the responses of grapevines in response to cold stress causing the limited growth and development, differentially expressed genes (DEGs) were screened through transcriptome analysis of shoots from 2 grapevine cultivars (‘Campbell Early’ and ‘Muscat Baily A’) kept at -2°C for 4 days. In gene ontology analysis of DEGs from ‘Campbell Early’, there were 17,424 clones related with biological process, 28,954 with cellular component, and 6,972 with molecular function genes in response to freezing temperature. The major induced genes included dehydrin xero 1, K-box region and MADS-box transcription factor family protein, and MYB domain protein 36, and inhibited genes included light-harvesting chlorophyll B-binding protein 3, FASCICLIN-like arabinoogalactan 9, and pectin methylesterase 61 in ‘Campbell Early’ grapevines. In gene ontology analysis of DEGs from ‘Muscat Baily A’, there were 1,157 clones related with biological process, 1,350 with cellular component, and 431 with molecular function gene. The major induced genes of ‘Muscat Baily A’ included NB-ARC domain-containing disease resistance protein, fatty acid hydrozylase superfamily, and isopentenyltransferase 3, and inhibited genes included binding, IAP-like protein 1, and pentatricopeptide repeat superfamily protein. All major DEGs were shown to be expressed differentially by freezing temperature in real time-PCR analysis. Protein domain analysis using InterPro Scan revealed that ubiquitin-protein ligase was redundant in both tested grapevines. Transcriptome profile of shoots exposed to cold can provide new insights into the molecular basis of tolerance to low-temperature in grapevines, and can be used as resources for development new grapevines tolerant to coldness. 환경스트레스 중의 하나인 저온에 대한 생육기의 포도나무의 반응을 분석하고자 -2°C에서 4일 동안 저온처리 한두 품종(‘Campbell Early’와 ‘Muscat Baily A’)의 포도나무잎을 이용하여 전사체를 분석하였고 특이발현유전자(differentially expressed genes, DEGs)를 검색하였다. 영하의 저온에 반응한 ‘Campbell Early’의 DEG를 기능별로 분석한결과 생물대사에서 17,424개, 세포구성에서 28,954개, 분자기능에서는 6,972개의 유전자와 관련이 있었다. 발현이 유도되는 유전자로는 dehydrin xero 1, K-box region and MADS-box transcription factor family protein과 MYB domain protein 36이 있으며, 억제되는 유전자로는 light-harvesting chlorophyll B-binding protein 3, FASCICLIN-like arabinoogalactan 9와 pectin methylesterase 61 등이 있었다. ‘Muscat Baily A’ 의 DEG는 생물대사에서 1,157개, 세포구성에서 1,350개, 분자기능에서는 431개의 유전자와 관련이 있었다. 발현이 유도되는 유전자로는 NB-ARC domain-containing disease resistance protein, fatty acid hydrozylase syperfamily와 isopentenyltransferase 3이 있으며, 억제되는 유전자로는 binding, IAP-like protein 1과 pentatricopeptide repeat superfamily protein 등이 있었다. Real-time PCR을 이용하여 영하의 저온에서특이적으로 발현하는 유전자들을 검정하였으며, InterPro Scan을 통해 단백질 도메인을 분석한 결과 두 품종 모두에서 ubiquitin-protein ligase가 가장 많았다. 영하의 저온에노출된 신초의 전사체 정보를 바탕으로 포도나무에서 저온 내성을 발현하는 기작을 연하는 데에 분자수준의 정보를 제공하고, 내한성 포도를 육종하는데 이용될 수 있을 것이다.

영하의 저온에 노출된 'Campbell Early'와 'Muscat Bailey A' 포도나무 신초의 전사체 비교

김선애,윤해근,Kim, Seon Ae,Yun, Hae Keun 한국식물생명공학회 2016 식물생명공학회지 Vol.43 No.2

환경스트레스 중의 하나인 저온에 대한 생육기의 포도나무의 반응을 분석하고자 -$2^{\circ}C$에서 4일 동안 저온처리 한두 품종('Campbell Early'와 'Muscat Baily A')의 포도나무잎을 이용하여 전사체를 분석하였고 특이발현유전자(differentially expressed genes, DEGs)를 검색하였다. 영하의 저온에 반응한 'Campbell Early'의 DEG를 기능별로 분석한 결과 생물대사에서 17,424개, 세포구성에서 28,954개, 분자기능에서는 6,972개의 유전자와 관련이 있었다. 발현이 유도되는 유전자로는 dehydrin xero 1, K-box region and MADS-box transcription factor family protein과 MYB domain protein 36이 있으며, 억제되는 유전자로는 light-harvesting chlorophyll B-binding protein 3, FASCICLIN-like arabinoogalactan 9와 pectin methylesterase 61 등이 있었다. 'Muscat Baily A'의 DEG는 생물대사에서 1,157개, 세포구성에서 1,350개, 분자기능에서는 431개의 유전자와 관련이 있었다. 발현이 유도되는 유전자로는 NB-ARC domain-containing disease resistance protein, fatty acid hydrozylase syperfamily와 isopentenyltransferase 3이 있으며, 억제되는 유전자로는 binding, IAP-like protein 1과 pentatricopeptide repeat superfamily protein 등이 있었다. Real-time PCR을 이용하여 영하의 저온에서 특이적으로 발현하는 유전자들을 검정하였으며, InterPro Scan을 통해 단백질 도메인을 분석한 결과 두 품종 모두에서 ubiquitin-protein ligase가 가장 많았다. 영하의 저온에 노출된 신초의 전사체 정보를 바탕으로 포도나무에서 저온 내성을 발현하는 기작을 연하는 데에 분자수준의 정보를 제공하고, 내한성 포도를 육종하는데 이용될 수 있을 것이다. To understand the responses of grapevines in response to cold stress causing the limited growth and development, differentially expressed genes (DEGs) were screened through transcriptome analysis of shoots from 2 grapevine cultivars ('Campbell Early' and 'Muscat Baily A') kept at -$2^{\circ}C$ for 4 days. In gene ontology analysis of DEGs from 'Campbell Early', there were 17,424 clones related with biological process, 28,954 with cellular component, and 6,972 with molecular function genes in response to freezing temperature. The major induced genes included dehydrin xero 1, K-box region and MADS-box transcription factor family protein, and MYB domain protein 36, and inhibited genes included light-harvesting chlorophyll B-binding protein 3, FASCICLIN-like arabinoogalactan 9, and pectin methylesterase 61 in 'Campbell Early' grapevines. In gene ontology analysis of DEGs from 'Muscat Baily A', there were 1,157 clones related with biological process, 1,350 with cellular component, and 431 with molecular function gene. The major induced genes of 'Muscat Baily A' included NB-ARC domain-containing disease resistance protein, fatty acid hydrozylase superfamily, and isopentenyltransferase 3, and inhibited genes included binding, IAP-like protein 1, and pentatricopeptide repeat superfamily protein. All major DEGs were shown to be expressed differentially by freezing temperature in real time-PCR analysis. Protein domain analysis using InterPro Scan revealed that ubiquitin-protein ligase was redundant in both tested grapevines. Transcriptome profile of shoots exposed to cold can provide new insights into the molecular basis of tolerance to low-temperature in grapevines, and can be used as resources for development new grapevines tolerant to coldness.

Dose-response functional gene analysis by exposure to 3 different polycyclic aromatic hydrocarbons in human hepatocytes

송미경,김연정,송미,최한심,류재천 대한독성 유전단백체 학회 2011 Molecular & cellular toxicology Vol.7 No.3

Polycyclic aromatic hydrocarbons (PAHs)are known as carcinogen and have been studied to show modulation of gene expression by exposure to various PAHs. However, few studies have been reported on microarray analysis of dose-response relationships of gene expression patterns. For comprehensive examination of dose-response effects of PAHs on gene expression,we elicited the genes which were changed more than 1.5-fold by analysis of gene expression profiles in human hepatocellular carcinoma (HepG2) cells, exposed for 48 h to nontoxic (NT) and IC20 doses of 3 different PAHs (benzo[a]anthracene (B[a]A), benzo[k]fluoranthene (B[k]F) and indeno[1,2,3-c,d]pyrene (IND)) by using human oligonucleotide chip. Transcriptomic profiling shows different gene expression patterns in NT and IC_(20) exposure groups and shows higher sensitivity to gene alteration in IC_(20) exposure group than NT group. Through the clustering analysis of gene expression profiles, we identified 7 up- and 3 down-regulated NT dose specific genes and 401 up- and 562 downregulated IC_(20) dose specific genes. After Gene Ontology (GO) analysis on IC_(20) dose specific genes, we determined several key pathways which are known as related to increase hepatotoxicity such as metabolism of xenobiotics by cytochrome P450, Jak-STAT signaling pathway, cytokine-cytokine receptor interaction and complement and coagulation cascade. But we did not find hepatotoxicity-related pathways through GO analysis on NT dose-specific genes. Genes that are expressed in only IC_(20) exposure group were regarded as biomarker of PAHs-induced hepatotoxicity. In conclusion,this study describes changes in gene expression profiles in hepatocytes in response to exposure to 3PAHs with different doses and relates these gene expression changes to hepatotoxicity related pathways. Moreover, potential new leads to genes and pathways that could play a role in liver disease prevention by PAHs were identified.

An Efficient Functional Analysis Method for Micro-array Data Using Gene Ontology

Hong, Dong-Wan,Lee, Jong-Keun,Park, Sung-Soo,Hong, Sang-Kyoon,Yoon, Jee-Hee Korea Information Processing Society 2007 Journal of information processing systems Vol.3 No.1

Microarray data includes tens of thousands of gene expressions simultaneously, so it can be effectively used in identifying the phenotypes of diseases. However, the retrieval of functional information from a large corpus of gene expression data is still a time-consuming task. In this paper, we propose an efficient method for identifying functional categories of differentially expressed genes from a micro-array experiment by using Gene Ontology (GO). Our method is as follows: (1) The expression data set is first filtered to include only genes with mean expression values that differ by at least 3-fold between the two groups. (2) The genes are then ranked based on the t-statistics. The 100 most highly ranked genes are selected as informative genes. (3) The t-value of each informative gene is imposed as a score on the associated GO terms. High-scoring GO terms are then listed with their associated genes and represent the functional category information of the micro-array experiment. A system called HMDA (Hallym Micro-array Data analysis) is implemented on publicly available micro-array data sets and validated. Our results were also compared with the original analysis.

Gene-set based genome-wide association analysis for the speed of sound in two skeletal sites of Korean women

( Ji Sun Kwon ),( Sang Soo Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2014 BMB Reports Vol.47 No.6

The speed of sound (SOS) value is an indicator of bone mineral density (BMD). Previous genome-wide association (GWA) studies have identified a number of genes, whose variations may affect BMD levels. However, their biological implications have been elusive. We re-analyzed the GWA study dataset for the SOS values in skeletal sites of 4,659 Korean women, using a gene-set analysis software, GSA-SNP. We identified 10 common representative GO terms, and 17 candidate genes between these two traits (PGS < 0.05). Implication of these GO terms and genes in the bone mechanism is well supported by the literature survey. Interestingly, the significance levels of some member genes were inversely related, in several gene-sets that were shared between two skeletal sites. This implies that biological process, rather than SNP or gene, is the substantial unit of genetic association for SOS in bone. In conclusion, our findings may provide new insights into the biological mechanisms for BMD. [BMB Reports 2014; 47(6): 348-353]