Kousaku Okubo

Publications of Kousaku Okubo

• The DNA Data Bank of Japan launches a new resource, the DDBJ Omics Archive of functional genomics experiments.

  Authors: Yuichi Kodama, Jun Mashima, Eli Kaminuma, Takashi Gojobori, Osamu Ogasawara, Toshihisa Takagi, Kousaku Okubo, Yasukazu Nakamura

  Nucleic acids research. 11/2011; 40(Database issue):D38-42.

  The DNA Data Bank of Japan (DDBJ; http://www.ddbj.nig.ac.jp) maintains and provides archival, retrieval and analytical resources for biological information. The central DDBJ resource consists ofThe DNA Data Bank of Japan (DDBJ; http://www.ddbj.nig.ac.jp) maintains and provides archival, retrieval and analytical resources for biological information. The central DDBJ resource consists of public, open-access nucleotide sequence databases including raw sequence reads, assembly information and functional annotation. Database content is exchanged with EBI and NCBI within the framework of the International Nucleotide Sequence Database Collaboration (INSDC). In 2011, DDBJ launched two new resources: the 'DDBJ Omics Archive' (DOR; http://trace.ddbj.nig.ac.jp/dor) and BioProject (http://trace.ddbj.nig.ac.jp/bioproject). DOR is an archival database of functional genomics data generated by microarray and highly parallel new generation sequencers. Data are exchanged between the ArrayExpress at EBI and DOR in the common MAGE-TAB format. BioProject provides an organizational framework to access metadata about research projects and the data from the projects that are deposited into different databases. In this article, we describe major changes and improvements introduced to the DDBJ services, and the launch of two new resources: DOR and BioProject.

• DDBJ progress report.

  Authors: Eli Kaminuma, Takehide Kosuge, Yuichi Kodama, Hideo Aono, Jun Mashima, Takashi Gojobori, Hideaki Sugawara, Osamu Ogasawara, Toshihisa Takagi, Kousaku Okubo, Yasukazu Nakamura

  Nucleic acids research. 11/2010; 39(Database issue):D22-7.

  The DNA Data Bank of Japan (DDBJ, http://www.ddbj.nig.ac.jp) provides a nucleotide sequence archive database and accompanying database tools for sequence submission, entry retrieval and annotationThe DNA Data Bank of Japan (DDBJ, http://www.ddbj.nig.ac.jp) provides a nucleotide sequence archive database and accompanying database tools for sequence submission, entry retrieval and annotation analysis. The DDBJ collected and released 3,637,446 entries/2,272,231,889 bases between July 2009 and June 2010. A highlight of the released data was archive datasets from next-generation sequencing reads of Japanese rice cultivar, Koshihikari submitted by the National Institute of Agrobiological Sciences. In this period, we started a new archive for quantitative genomics data, the DDBJ Omics aRchive (DOR). The DOR stores quantitative data both from the microarray and high-throughput new sequencing platforms. Moreover, we improved the content of the DDBJ patent sequence, released a new submission tool of the DDBJ Sequence Read Archive (DRA) which archives massive raw sequencing reads, and enhanced a cloud computing-based analytical system from sequencing reads, the DDBJ Read Annotation Pipeline. In this article, we describe these new functions of the DDBJ databases and support tools.

• DDBJ launches a new archive database with analytical tools for next-generation sequence data.

  Authors: Eli Kaminuma, Jun Mashima, Yuichi Kodama, Takashi Gojobori, Osamu Ogasawara, Kousaku Okubo, Toshihisa Takagi, Yasukazu Nakamura

  Nucleic acids research. 10/2009;

  The DNA Data Bank of Japan (DDBJ) (http://www.ddbj.nig.ac.jp) has collected and released 1 701 110 entries/1 116 138 614 bases between July 2008 and June 2009. A few highlighted data releases fromThe DNA Data Bank of Japan (DDBJ) (http://www.ddbj.nig.ac.jp) has collected and released 1 701 110 entries/1 116 138 614 bases between July 2008 and June 2009. A few highlighted data releases from DDBJ were the complete genome sequence of an endosymbiont within protist cells in the termite gut and Cap Analysis Gene Expression tags for human and mouse deposited from the Functional Annotation of the Mammalian cDNA consortium. In this period, we started a novel user announcement service using Really Simple Syndication (RSS) to deliver a list of data released from DDBJ on a daily basis. Comprehensive visualization of a DDBJ release data was attempted by using a word cloud program. Moreover, a new archive for sequencing data from next-generation sequencers, the 'DDBJ Read Archive' (DRA), was launched. Concurrently, for read data registered in DRA, a semi-automatic annotation tool called the 'DDBJ Read Annotation Pipeline' was released as a preliminary step. The pipeline consists of two parts: basic analysis for reference genome mapping and de novo assembly and high-level analysis of structural and functional annotations. These new services will aid users' research and provide easier access to DDBJ databases.

• On theoretical models of gene expression evolution with random genetic drift and natural selection.

  Authors: Osamu Ogasawara, Kousaku Okubo

  PloS one. 01/2009; 4(11):e7943.

  BACKGROUND: The relative contributions of natural selection and random genetic drift are a major source of debate in the study of gene expression evolution, which is hypothesized to serve as a bridgeBACKGROUND: The relative contributions of natural selection and random genetic drift are a major source of debate in the study of gene expression evolution, which is hypothesized to serve as a bridge from molecular to phenotypic evolution. It has been suggested that the conflict between views is caused by the lack of a definite model of the neutral hypothesis, which can describe the long-run behavior of evolutionary change in mRNA abundance. Therefore previous studies have used inadequate analogies with the neutral prediction of other phenomena, such as amino acid or nucleotide sequence evolution, as the null hypothesis of their statistical inference. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we introduced two novel theoretical models, one based on neutral drift and the other assuming natural selection, by focusing on a common property of the distribution of mRNA abundance among a variety of eukaryotic cells, which reflects the result of long-term evolution. Our results demonstrated that (1) our models can reproduce two independently found phenomena simultaneously: the time development of gene expression divergence and Zipf's law of the transcriptome; (2) cytological constraints can be explicitly formulated to describe long-term evolution; (3) the model assuming that natural selection optimized relative mRNA abundance was more consistent with previously published observations than the model of optimized absolute mRNA abundances. CONCLUSIONS/SIGNIFICANCE: The models introduced in this study give a formulation of evolutionary change in the mRNA abundance of each gene as a stochastic process, on the basis of previously published observations. This model provides a foundation for interpreting observed data in studies of gene expression evolution, including identifying an adequate time scale for discriminating the effect of natural selection from that of random genetic drift of selectively neutral variations.

• BodyParts3D: 3D structure database for anatomical concepts.

  Authors: Nobutaka Mitsuhashi, Kaori Fujieda, Takuro Tamura, Shoko Kawamoto, Toshihisa Takagi, Kousaku Okubo

  Nucleic acids research. 11/2008;

  BodyParts3D is a dictionary-type database for anatomy in which anatomical concepts are represented by 3D structure data that specify corresponding segments of a 3D whole-body model for an adult humanBodyParts3D is a dictionary-type database for anatomy in which anatomical concepts are represented by 3D structure data that specify corresponding segments of a 3D whole-body model for an adult human male. It encompasses morphological and geometrical knowledge in anatomy and complements ontological representation. Moreover, BodyParts3D introduces a universal coordinate system in human anatomy, which may facilitate management of samples and data in biomedical research and clinical practice. As of today, 382 anatomical concepts, sufficient for mapping materials in most molecular medicine experiments, have been specified. Expansion of the dictionary by adding further segments and details to the whole-body model will continue in collaboration with clinical researchers until sufficient resolution and accuracy for most clinical application are achieved. BodyParts3D is accessible at: http://lifesciencedb.jp/ag/bp3d/.

• Gene-LfEXPO: a Tool to Extract Knowledge From Transcriptomes and Find eLiterature-Sparsef Relationships Between Genes and Tissues.

  Authors: Teruyoshi Hishiki, Issei Tamada, Kousaku Okubo

  AMIA ... Annual Symposium proceedings / AMIA Symposium. AMIA Symposium. 02/2008;

  The increasing volume and diversity of transcriptome data in the public domain offer an opportunity to advance new questions and hypotheses. We anticipate that tools that can visualize the gap in theThe increasing volume and diversity of transcriptome data in the public domain offer an opportunity to advance new questions and hypotheses. We anticipate that tools that can visualize the gap in the distribution of information between the scientific literature and actual data would prompt such questions. We focused on the roles played by various genes in tissues, and have developed a database that contrasts information on gene expression in tissues with PubMed text and transcriptome data. Data pairs of tissues and the genes that might be expressed there were automatically extracted from text with vocabularies for the genes and tissues. The anatomical categories of various expressed sequence tag (EST) libraries were also automatically determined. These types of information were linked using the hierarchical structure of the Metathesaurus in UMLS. The database, named Gene-LfEXPO, is accessible at http://www.genelexpo.jp.

• DDBJ with new system and face.

  Authors: Hideaki Sugawara, Osamu Ogasawara, Kousaku Okubo, Takashi Gojobori, Yoshio Tateno

  Nucleic Acids Research. 01/2008; 36:22-24.

• Cornichon-like protein facilitates secretion of HB-EGF and regulates proper development of cranial nerves.

  Authors: Hideharu Hoshino, Tsukasa Uchida, Toshiaki Otsuki, Shoko Kawamoto, Kousaku Okubo, Masatoshi Takeichi, Osamu Chisaka

  Molecular biology of the cell. 05/2007; 18(4):1143-52.

  During their migration to the periphery, cranial neural crest cells (NCCs) are repulsed by an ErbB4-dependent cue(s) in the mesenchyme adjoining rhombomeres (r) 3 and 5, which are segmented hindbrainDuring their migration to the periphery, cranial neural crest cells (NCCs) are repulsed by an ErbB4-dependent cue(s) in the mesenchyme adjoining rhombomeres (r) 3 and 5, which are segmented hindbrain neuromeres. ErbB4 has many ligands, but which ligand functions in the above system has not yet been clearly determined. Here we found that a cornichon-like protein/cornichon homolog 2 (CNIL/CNIH2) gene was expressed in the developing chick r3 and r5. In a cell culture system, its product facilitated the secretion of heparin-binding epidermal growth factor-like growth factor (HB-EGF), one of the ligands of ErbB4. When CNIL function was perturbed in chick embryos by forced expression of a truncated form of CNIL, the distribution of NCCs was affected, which resulted in abnormal nerve fiber connections among the cranial sensory ganglia. Also, knockdown of CNIL or HB-EGF with siRNAs yielded a similar phenotype. This phenotype closely resembled that of ErbB4 knockout mouse embryos. Because HB-EGF was uniformly expressed in the embryonic hindbrain, CNIL seems to confine the site of HB-EGF action to r3 and r5 in concert with ErbB4.

• DDBJ in preparation for overview of research activities behind data submissions.

  Authors: Kousaku Okubo, Hideaki Sugawara, Takashi Gojobori, Yoshio Tateno

  Nucleic acids research. 02/2006; 34(Database issue):D6-9.

  In the past year, DDBJ (http://www.ddbj.nig.ac.jp) collected and released 1,956,826 entries or 1,741,313,111 bases. The released data include approximately 90,000 ESTs and cDNAs of MacacaIn the past year, DDBJ (http://www.ddbj.nig.ac.jp) collected and released 1,956,826 entries or 1,741,313,111 bases. The released data include approximately 90,000 ESTs and cDNAs of Macaca fascicularis, and 280 million bases of mouse GSS. In addition to the data collection, we have indexed the submitted data to the International Nucleotide Sequence Database Collaboration (INSDC, http://www.insdc.org) to classify the entries into research projects behind data submissions. They are expected to be useful to the data submitters and users for enhancing the data submission, retrieval and systematic data analyses at INSDC. The results of indexing also allow one to grasp research projects in life sciences that promoted and produced the DNA sequences submitted to INSDC.

• BodyMap-Xs: anatomical breakdown of 17 million animal ESTs for cross-species comparison of gene expression.

  Authors: Osamu Ogasawara, Makiko Otsuji, Kouji Watanabe, Takayasu Iizuka, Takuro Tamura, Teruyoshi Hishiki, Shoko Kawamoto, Kousaku Okubo

  Nucleic acids research. 02/2006; 34(Database issue):D628-31.

  BodyMap-Xs (http://bodymap.jp) is a database for cross-species gene expression comparison. It was created by the anatomical breakdown of 17 million animal expressed sequence tag (EST) records in DDBJBodyMap-Xs (http://bodymap.jp) is a database for cross-species gene expression comparison. It was created by the anatomical breakdown of 17 million animal expressed sequence tag (EST) records in DDBJ using a sorting program tailored for this purpose. In BodyMap-Xs, users are allowed to compare the expression patterns of orthologous and paralogous genes in a coherent manner. This will provide valuable insights for the evolutionary study of gene expression and identification of a responsive motif for a particular expression pattern. In addition, starting from a concise overview of the taxonomical and anatomical breakdown of all animal ESTs, users can navigate to obtain gene expression ranking of a particular tissue in a particular animal. This method may lead to the understanding of the similarities and differences between the homologous tissues across animal species. BodyMap-Xs will be automatically updated in synchronization with the major update in DDBJ, which occurs periodically.

• [Human transcriptome]

  Authors: Motohiko Tanino, Yutaka Suzuki, Tadashi Imanishi, Teruyoshi Hishiki, Kousaku Okubo, Takashi Gojobori, Sumio Sugano

  Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme. 01/2006; 50(16 Suppl):2059-64.

• The Human Anatomic Gene Expression Library (H-ANGEL), the H-Inv integrative display of human gene expression across disparate technologies and platforms.

  Authors: Motohiko Tanino, Marie-Anne Debily, Takuro Tamura, Teruyoshi Hishiki, Osamu Ogasawara, Katsuji Murakawa, Shoko Kawamoto, Kouichi Itoh, Shinya Watanabe, Sandro José de Souza [......] Eric Eveno, Phillip Hilton, Yukio Sudo, Janet Kelso, Kazuho Ikeo, Tadashi Imanishi, Takashi Gojobori, Charles Auffray, Winston Hide, Kousaku Okubo

  Nucleic acids research. 02/2005; 33(Database issue):D567-72.

  The Human Anatomic Gene Expression Library (H-ANGEL) is a resource for information concerning the anatomical distribution and expression of human gene transcripts. The tool contains proteinThe Human Anatomic Gene Expression Library (H-ANGEL) is a resource for information concerning the anatomical distribution and expression of human gene transcripts. The tool contains protein expression data from multiple platforms that has been associated with both manually annotated full-length cDNAs from H-InvDB and RefSeq sequences. Of the H-Inv predicted genes, 18 897 have associated expression data generated by at least one platform. H-ANGEL utilizes categorized mRNA expression data from both publicly available and proprietary sources. It incorporates data generated by three types of methods from seven different platforms. The data are provided to the user in the form of a web-based viewer with numerous query options. H-ANGEL is updated with each new release of cDNA and genome sequence build. In future editions, we will incorporate the capability for expression data updates from existing and new platforms. H-ANGEL is accessible at http://www.jbirc.aist.go.jp/hinv/h-angel/.

• DDBJ in collaboration with mass-sequencing teams on annotation.

  Authors: Yoshio Tateno, Naruya Saitou, Kousaku Okubo, Hideaki Sugawara, Takashi Gojobori

  Nucleic Acids Research. 01/2005; 33:25-28.

• Integrative annotation of 21,037 human genes validated by full-length cDNA clones.

  Authors: Tadashi Imanishi, Takeshi Itoh, Yutaka Suzuki, Claire O'Donovan, Satoshi Fukuchi, Kanako O Koyanagi, Roberto A Barrero, Takuro Tamura, Yumi Yamaguchi-Kabata, Motohiko Tanino [......] Rolf Apweiler, Kousaku Okubo, Lukas Wagner, Stefan Wiemann, Robert L Strausberg, Takao Isogai, Charles Auffray, Nobuo Nomura, Takashi Gojobori, Sumio Sugano

  PLoS biology. 07/2004; 2(6):e162.

  The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in thisThe human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.

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• Identification and characterization of a novel component of the cornified envelope, cornifelin.

  Authors: Hideo Michibata, Hiroaki Chiba, Koji Wakimoto, Mariko Seishima, Satoshi Kawasaki, Kousaku Okubo, Hiroshi Mitsui, Hideshi Torii, Yuji Imai

  Biochemical and biophysical research communications. 07/2004; 318(4):803-13.

  Psoriasis is recognized as a chronic inflammatory disease characterized by epidermal hyperproliferation. To identify psoriasis-related genes, we compared the mRNA populations of normal and psoriaticPsoriasis is recognized as a chronic inflammatory disease characterized by epidermal hyperproliferation. To identify psoriasis-related genes, we compared the mRNA populations of normal and psoriatic skin. We identified one gene, designated as cornifelin, which showed increased expression in psoriatic skin. Human cornifelin contains 112 amino acids and is expressed in the uterus, cervix, and skin. In situ hybridization analysis demonstrated the presence of human cornifelin in the granular cell layer of the epidermis. To investigate the function of cornifelin, we established a transgenic mouse line overexpressing human cornifelin. Using these mice, we have shown that cornifelin is directly or indirectly cross-linked to at least two other cornified envelope proteins, loricrin and involucrin, in vivo. Overexpression of human cornifelin correlated with decreased loricrin expression and increased involucrin expression in the transgenic mouse. However, abnormality of epidermal differentiation was not observed in the transgenic mouse.

• Cloning of a gene for a novel epithelium-specific cytosolic phospholipase A2, cPLA2delta, induced in psoriatic skin.

  Authors: Hiroaki Chiba, Hideo Michibata, Koji Wakimoto, Mariko Seishima, Satoshi Kawasaki, Kousaku Okubo, Hiroshi Mitsui, Hideshi Torii, Yuji Imai

  The Journal of biological chemistry. 04/2004; 279(13):12890-7.

  Psoriasis is a common skin disease characterized by hyperplastic regenerative epidermal growth and infiltration of immunocytes. The etiology of psoriasis is unknown, although several genetic andPsoriasis is a common skin disease characterized by hyperplastic regenerative epidermal growth and infiltration of immunocytes. The etiology of psoriasis is unknown, although several genetic and cellular factors have been elucidated. To find new psoriasis-related genes, we have cloned cDNAs that are differentially expressed between normal and psoriatic skins. Among these clones, we have identified a new gene that codes for a new member of the type IV cytosolic phospholipase A(2) (cPLA(2)) family. We refer to this gene as cPLA(2)delta. It encodes a polypeptide of 818 amino acids that has significant homology with known cPLA(2) proteins in the C2 and catalytic domains. The cPLA(2)delta gene was mapped to the 15q13-14 chromosomal locus, near to the locus of the cPLA(2)beta gene, from which it is separated by a physical distance of about 220 kb. To identify the phospholipase A(2) activity of cPLA(2)delta, we transfected COS-7 cells with His-tagged cPLA(2)delta. The cell lysate from these cells had calcium-dependent phospholipase A(2) activity. Northern blot analysis revealed that a cPLA(2)delta transcript of about 4 kb is expressed in stratified squamous epithelia, such as those in skin and cervix, but not in other tissues. In situ hybridization and immunohistochemistry revealed that cPLA(2)delta is expressed strongly in the upper spinous layer of the psoriatic epidermis, expressed weakly and discontinuously in atopic dermatitis and mycosis fungoides, and not detected in the epidermis of normal skin; cPLA(2)alpha is not detected in either normal or psoriatic skin. These results suggest that cPLA(2)delta exhibits a unique distribution pattern compared with that of known cPLA(2) subtypes, and it may play a critical role in inflammation in psoriatic lesions.

• Indexing anatomical concepts to OMIM Clinical Synopsis using the UMLS Metathesaurus.

  Authors: Teruyoshi Hishiki, Osamu Ogasawara, Yoshimasa Tsuruoka, Kousaku Okubo

  In silico biology. 02/2004; 4(1):31-54.

  As a first step toward the quantitative comparison of clinical features of diseases, we indexed the text descriptions in the Clinical Synopsis section of the Online Mendelian Inheritance in ManAs a first step toward the quantitative comparison of clinical features of diseases, we indexed the text descriptions in the Clinical Synopsis section of the Online Mendelian Inheritance in Man (OMIM) with concepts for the body parts, organs, and tissues contained in the Metathesaurus of the Unified Medical Language System (UMLS). We also indexed the text with the diseases and disorders having links to body parts specified in the thesaurus. The vocabulary size was approximately 177,540 representations for 81,435 concepts, and 2,161 concepts were indexed to 3,779 OMIM entries. The indexed concepts included 134 concepts for the noun forms of anatomical concepts and 985 indexed concepts for diseases and disorders that were linked to 132 and 408 anatomical concepts, respectively. We report herein that the retrieval of OMIM entries for diseases affecting specific organs can be made more comprehensive through the anatomical concepts indexed to the Clinical Synopsis or linked to the indexed concepts, as compared to simply matching organ names to the Clinical Synopsis text. The recall and precision of identifying relevant body parts in the Clinical Synopsis were calculated as 78% and 92.5%, respectively, based on random sampling. The examination of the unidentified body parts due to lack of indexed diseases and disorders showed that although most of the concepts for diseases and disorders were contained in the Metathesaurus, their relations to body parts were not. The indexing result proved the effectiveness of the Metathesaurus as a resource for the identification of concepts indicating body parts, diseases, and disorders.

• Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones

  Authors: Tadashi Imanishi, Takeshi Itoh, Yutaka Suzuki, Claire O'Donovan, Satoshi Fukuchi, Koyanagi Kanako O, Barrero Roberto A, Takuro Tamura, Yumi Yamaguchi-Kabata, Motohiko Tanino [......] Rolf Apweiler, Kousaku Okubo, Lukas Wagner, Stefan Wiemann, Strausberg Robert L, Takao Isogai, Charles Auffray, Nobuo Nomura, Takashi Gojobori, Sumio Sugano

  PLoS Biology. 01/2004;

  The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in thisThe human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/ ). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.

• A novel diacylglycerol acyltransferase (DGAT2) is decreased in human psoriatic skin and increased in diabetic mice.

  Authors: Koji Wakimoto, Hiroaki Chiba, Hideo Michibata, Mariko Seishima, Satoshi Kawasaki, Kousaku Okubo, Hiroshi Mitsui, Hideshi Torii, Yuji Imai

  Biochemical and biophysical research communications. 11/2003; 310(2):296-302.

  Psoriasis is a skin disease with epidermal keratinocyte hyperproliferation and altered differentiation. To identify novel psoriasis-related genes, we investigated differentially expressed genesPsoriasis is a skin disease with epidermal keratinocyte hyperproliferation and altered differentiation. To identify novel psoriasis-related genes, we investigated differentially expressed genes between normal and psoriatic skin. We identified a novel acyl CoA:diacylglycerol acyltransferase 2 (DGAT2) gene, which was decreased in human psoriatic skin. DGAT2 mRNA was expressed in sebaceous glands of normal human skin. DGAT2 protein was detected on endoplasmic reticulum. DGAT2 catalyzes the final step in the production of triglycerides and the accumulation of triglycerides in the tissues is considered to be related to insulin resistance. Therefore, we also investigated the expression of the DGAT2 gene in diabetic mice. DGAT2 mRNA was increased in the adipose, small intestine, and skeletal muscle in diabetic mice.

• Integration of Diverse Knowledge and Data

  Authors: Yoshimasa Tsuruoka, Teruyoshi Hishiki, Osamu Ogasawara, Kousaku Okubo

  08/2003;

  After the accomplishment of human draft sequence, more and more efforts are being made in the mapping of the data-driven patterns to background knowledge, hoping to efficiently produce hypotheses outAfter the accomplishment of human draft sequence, more and more efforts are being made in the mapping of the data-driven patterns to background knowledge, hoping to efficiently produce hypotheses out of the flood of data. Here we propose a framework of biomedical data and knowledge that has a high adaptability to the automated data interpretation. Then, we show that biomedical databases with heterogeneous scopes and structures can be converted to the format, and possible roles of ontology of biomedical objects combined with natural language processing techniques. Lastly, we present applications of formatted biomedical knowledge to scientific discovery.