Mitsuteru Nakao

Publications of Mitsuteru Nakao

• Complete Genome Sequence of Bradyrhizobium sp. S23321: Insights into Symbiosis Evolution in Soil Oligotrophs.

  Authors: Takashi Okubo, Takahiro Tsukui, Hiroko Maita, Shinobu Okamoto, Kenshiro Oshima, Takatomo Fujisawa, Akihiro Saito, Hiroyuki Futamata, Reiko Hattori, Yumi Shimomura [......] Yuko Takada Hoshino, Hideki Hirakawa, Hisayuki Mitsui, Kimihiro Terasawa, Manabu Itakura, Shusei Sato, Wakako Ikeda-Ohtsubo, Natsuko Sakakura, Eli Kaminuma, Kiwamu Minamisawa

  Microbes and environments / JSME. 03/2012;

  Bradyrhizobium sp. S23321 is an oligotrophic bacterium isolated from paddy field soil. Although S23321 is phylogenetically close to Bradyrhizobium japonicum USDA110, a legume symbiont, it is unableBradyrhizobium sp. S23321 is an oligotrophic bacterium isolated from paddy field soil. Although S23321 is phylogenetically close to Bradyrhizobium japonicum USDA110, a legume symbiont, it is unable to induce root nodules in siratro, a legume often used for testing Nod factor-dependent nodulation. The genome of S23321 is a single circular chromosome, 7,231,841 bp in length, with an average GC content of 64.3%. The genome contains 6,898 potential protein-encoding genes, one set of rRNA genes, and 45 tRNA genes. Comparison of the genome structure between S23321 and USDA110 showed strong colinearity; however, the symbiosis islands present in USDA110 were absent in S23321, whose genome lacked a chaperonin gene cluster (groELS3) for symbiosis regulation found in USDA110. A comparison of sequences around the tRNA-Val gene strongly suggested that S23321 contains an ancestral-type genome that precedes the acquisition of a symbiosis island by horizontal gene transfer. Although S23321 contains a nif (nitrogen fixation) gene cluster, the organization, homology, and phylogeny of the genes in this cluster were more similar to those of photosynthetic bradyrhizobia ORS278 and BTAi1 than to those on the symbiosis island of USDA110. In addition, we found genes encoding a complete photosynthetic system, many ABC transporters for amino acids and oligopeptides, two types (polar and lateral) of flagella, multiple respiratory chains, and a system for lignin monomer catabolism in the S23321 genome. These features suggest that S23321 is able to adapt to a wide range of environments, probably including low-nutrient conditions, with multiple survival strategies in soil and rhizosphere.

• The 2nd DBCLS BioHackathon: interoperable bioinformatics Web services for integrated applications.

  Authors: Toshiaki Katayama, Mark D Wilkinson, Rutger Vos, Takeshi Kawashima, Shuichi Kawashima, Mitsuteru Nakao, Yasunori Yamamoto, Hong-Woo Chun, Atsuko Yamaguchi, Shin Kawano [......] Martin Senger, Jessica Severin, Yasumasa Shigemoto, Hideaki Sugawara, James Taylor, Oswaldo Trelles, Chisato Yamasaki, Riu Yamashita, Noriyuki Satoh, Toshihisa Takagi

  Journal of biomedical semantics. 08/2011; 2:4.

  ABSTRACT: The interaction between biological researchers and the bioinformatics tools they use is still hampered by incomplete interoperability between such tools. To ensure interoperabilityABSTRACT: The interaction between biological researchers and the bioinformatics tools they use is still hampered by incomplete interoperability between such tools. To ensure interoperability initiatives are effectively deployed, end-user applications need to be aware of, and support, best practices and standards. Here, we report on an initiative in which software developers and genome biologists came together to explore and raise awareness of these issues: BioHackathon 2009. Developers in attendance came from diverse backgrounds, with experts in Web services, workflow tools, text mining and visualization. Genome biologists provided expertise and exemplar data from the domains of sequence and pathway analysis and glyco-informatics. One goal of the meeting was to evaluate the ability to address real world use cases in these domains using the tools that the developers represented. This resulted in i) a workflow to annotate 100,000 sequences from an invertebrate species; ii) an integrated system for analysis of the transcription factor binding sites (TFBSs) enriched based on differential gene expression data obtained from a microarray experiment; iii) a workflow to enumerate putative physical protein interactions among enzymes in a metabolic pathway using protein structure data; iv) a workflow to analyze glyco-gene-related diseases by searching for human homologs of glyco-genes in other species, such as fruit flies, and retrieving their phenotype-annotated SNPs. Beyond deriving prototype solutions for each use-case, a second major purpose of the BioHackathon was to highlight areas of insufficiency. We discuss the issues raised by our exploration of the problem/solution space, concluding that there are still problems with the way Web services are modeled and annotated, including: i) the absence of several useful data or analysis functions in the Web service "space"; ii) the lack of documentation of methods; iii) lack of compliance with the SOAP/WSDL specification among and between various programming-language libraries; and iv) incompatibility between various bioinformatics data formats. Although it was still difficult to solve real world problems posed to the developers by the biological researchers in attendance because of these problems, we note the promise of addressing these issues within a semantic framework.

• BioRuby: bioinformatics software for the Ruby programming language.

  Authors: Naohisa Goto, Pjotr Prins, Mitsuteru Nakao, Raoul Bonnal, Jan Aerts, Toshiaki Katayama

  Bioinformatics (Oxford, England). 10/2010; 26(20):2617-9.

  The BioRuby software toolkit contains a comprehensive set of free development tools and libraries for bioinformatics and molecular biology, written in the Ruby programming language. BioRuby hasThe BioRuby software toolkit contains a comprehensive set of free development tools and libraries for bioinformatics and molecular biology, written in the Ruby programming language. BioRuby has components for sequence analysis, pathway analysis, protein modelling and phylogenetic analysis; it supports many widely used data formats and provides easy access to databases, external programs and public web services, including BLAST, KEGG, GenBank, MEDLINE and GO. BioRuby comes with a tutorial, documentation and an interactive environment, which can be used in the shell, and in the web browser. BioRuby is free and open source software, made available under the Ruby license. BioRuby runs on all platforms that support Ruby, including Linux, Mac OS X and Windows. And, with JRuby, BioRuby runs on the Java Virtual Machine. The source code is available from http://www.bioruby.org/. katayama@bioruby.org

• TogoWS: integrated SOAP and REST APIs for interoperable bioinformatics Web services.

  Authors: Toshiaki Katayama, Mitsuteru Nakao, Toshihisa Takagi

  Nucleic acids research. 07/2010; 38(Web Server issue):W706-11.

  Web services have become widely used in bioinformatics analysis, but there exist incompatibilities in interfaces and data types, which prevent users from making full use of a combination of theseWeb services have become widely used in bioinformatics analysis, but there exist incompatibilities in interfaces and data types, which prevent users from making full use of a combination of these services. Therefore, we have developed the TogoWS service to provide an integrated interface with advanced features. In the TogoWS REST (REpresentative State Transfer) API (application programming interface), we introduce a unified access method for major database resources through intuitive URIs that can be used to search, retrieve, parse and convert the database entries. The TogoWS SOAP API resolves compatibility issues found on the server and client-side SOAP implementations. The TogoWS service is freely available at: http://togows.dbcls.jp/.

• Natural Language Query Processing for Life Science Knowledge - Position Paper.

  Authors: Jin-Dong Kim, Yasunori Yamamoto, Atsuko Yamaguchi, Mitsuteru Nakao, Kenta Oouchida, Hong-Woo Chun, Toshihisa Takagi

  Active Media Technology, 6th International Conference, AMT 2010, Toronto, Canada, August 28-30, 2010. Proceedings; 01/2010

• The DBCLS BioHackathon: standardization and interoperability for bioinformatics web services and workflows. The DBCLS BioHackathon Consortium*.

  Authors: Toshiaki Katayama, Kazuharu Arakawa, Mitsuteru Nakao, Keiichiro Ono, Kiyoko F Aoki-Kinoshita, Yasunori Yamamoto, Atsuko Yamaguchi, Shuichi Kawashima, Hong-Woo Chun, Jan Aerts [......] Daron M Standley, Hideaki Sugawara, Toshiyuki Tashiro, Oswaldo Trelles, Rutger A Vos, Mark D Wilkinson, William York, Christian M Zmasek, Kiyoshi Asai, Toshihisa Takagi

  Journal of biomedical semantics. 01/2010; 1(1):8.

  Web services have become a key technology for bioinformatics, since life science databases are globally decentralized and the exponential increase in the amount of available data demands forWeb services have become a key technology for bioinformatics, since life science databases are globally decentralized and the exponential increase in the amount of available data demands for efficient systems without the need to transfer entire databases for every step of an analysis. However, various incompatibilities among database resources and analysis services make it difficult to connect and integrate these into interoperable workflows. To resolve this situation, we invited domain specialists from web service providers, client software developers, Open Bio* projects, the BioMoby project and researchers of emerging areas where a standard exchange data format is not well established, for an intensive collaboration entitled the BioHackathon 2008. The meeting was hosted by the Database Center for Life Science (DBCLS) and Computational Biology Research Center (CBRC) and was held in Tokyo from February 11th to 15th, 2008. In this report we highlight the work accomplished and the common issues arisen from this event, including the standardization of data exchange formats and services in the emerging fields of glycoinformatics, biological interaction networks, text mining, and phyloinformatics. In addition, common shared object development based on BioSQL, as well as technical challenges in large data management, asynchronous services, and security are discussed. Consequently, we improved interoperability of web services in several fields, however, further cooperation among major database centers and continued collaborative efforts between service providers and software developers are still necessary for an effective advance in bioinformatics web service technologies.

• CyanoBase: the cyanobacteria genome database update 2010.

  Authors: Mitsuteru Nakao, Shinobu Okamoto, Mitsuyo Kohara, Tsunakazu Fujishiro, Takatomo Fujisawa, Shusei Sato, Satoshi Tabata, Takakazu Kaneko, Yasukazu Nakamura

  Nucleic acids research. 10/2009;

  CyanoBase (http://genome.kazusa.or.jp/cyanobase) is the genome database for cyanobacteria, which are model organisms for photosynthesis. The database houses cyanobacteria species information,CyanoBase (http://genome.kazusa.or.jp/cyanobase) is the genome database for cyanobacteria, which are model organisms for photosynthesis. The database houses cyanobacteria species information, complete genome sequences, genome-scale experiment data, gene information, gene annotations and mutant information. In this version, we updated these datasets and improved the navigation and the visual display of the data views. In addition, a web service API now enables users to retrieve the data in various formats with other tools, seamlessly.

• Low conservation and species-specific evolution of alternative splicing in humans and mice: comparative genomics analysis using well-annotated full-length cDNAs.

  Authors: Jun-ichi Takeda, Yutaka Suzuki, Ryuichi Sakate, Yoshiharu Sato, Masahide Seki, Takuma Irie, Nono Takeuchi, Takuya Ueda, Mitsuteru Nakao, Sumio Sugano, Takashi Gojobori, Tadashi Imanishi

  Nucleic acids research. 11/2008;

  Using full-length cDNA sequences, we compared alternative splicing (AS) in humans and mice. The alignment of the human and mouse genomes showed that 86% of 199 426 total exons in human AS variantsUsing full-length cDNA sequences, we compared alternative splicing (AS) in humans and mice. The alignment of the human and mouse genomes showed that 86% of 199 426 total exons in human AS variants were conserved in the mouse genome. Of the 20 392 total human AS variants, however, 59% consisted of all conserved exons. Comparing AS patterns between human and mouse transcripts revealed that only 431 transcripts from 189 loci were perfectly conserved AS variants. To exclude the possibility that the full-length human cDNAs used in the present study, especially those with retained introns, were cloning artefacts or prematurely spliced transcripts, we experimentally validated 34 such cases. Our results indicate that even retained-intron type transcripts are typically expressed in a highly controlled manner and interact with translating ribosomes. We found non-conserved AS exons to be predominantly outside the coding sequences (CDSs). This suggests that non-conserved exons in the CDSs of transcripts cause functional constraint. These findings should enhance our understanding of the relationship between AS and species specificity of human genes.

• Genome Structure of the Legume, Lotus japonicus.

  Authors: Shusei Sato, Yasukazu Nakamura, Takakazu Kaneko, Erika Asamizu, Tomohiko Kato, Mitsuteru Nakao, Shigemi Sasamoto, Akiko Watanabe, Akiko Ono, Kumiko Kawashima [......] Chika Takahashi, Tsuyuko Wada, Manabu Yamada, Nobuko Ohmido, Makoto Hayashi, Kiichi Fukui, Tomoya Baba, Tomoko Nakamichi, Hirotada Mori, Satoshi Tabata

  DNA research : an international journal for rapid publication of reports on genes and genomes. 06/2008;

  The legume Lotus japonicus has been widely used as a model system to investigate the genetic background of legume-specific phenomena such as symbiotic nitrogen fixation. Here, we report structuralThe legume Lotus japonicus has been widely used as a model system to investigate the genetic background of legume-specific phenomena such as symbiotic nitrogen fixation. Here, we report structural features of the L. japonicus genome. The 315.1-Mb sequences determined in this and previous studies correspond to 67% of the genome (472 Mb), and are likely to cover 91.3% of the gene space. Linkage mapping anchored 130-Mb sequences onto the six linkage groups. A total of 10 951 complete and 19 848 partial structures of protein-encoding genes were assigned to the genome. Comparative analysis of these genes revealed the expansion of several functional domains and gene families that are characteristic of L. japonicus. Synteny analysis detected traces of whole-genome duplication and the presence of synteny blocks with other plant genomes to various degrees. This study provides the first opportunity to look into the complex and unique genetic system of legumes.

• The H-Invitational Database (H-InvDB), a comprehensive annotation resource for human genes and transcripts.

  Authors: Chisato Yamasaki, Katsuhiko Murakami, Yasuyuki Fujii, Yoshiharu Sato, Erimi Harada, Jun-ichi Takeda, Takayuki Taniya, Ryuichi Sakate, Shingo Kikugawa, Makoto Shimada [......] Yumi Yamaguchi-Kabata, Takeshi Itoh, Teruyoshi Hishiki, Satoshi Fukuchi, Ken Nishikawa, Sumio Sugano, Nobuo Nomura, Yoshio Tateno, Tadashi Imanishi, Takashi Gojobori

  Nucleic acids research. 02/2008; 36(Database issue):D793-9.

  Here we report the new features and improvements in our latest release of the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/), a comprehensive annotation resource for human genes andHere we report the new features and improvements in our latest release of the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/), a comprehensive annotation resource for human genes and transcripts. H-InvDB, originally developed as an integrated database of the human transcriptome based on extensive annotation of large sets of full-length cDNA (FLcDNA) clones, now provides annotation for 120 558 human mRNAs extracted from the International Nucleotide Sequence Databases (INSD), in addition to 54 978 human FLcDNAs, in the latest release H-InvDB_4.6. We mapped those human transcripts onto the human genome sequences (NCBI build 36.1) and determined 34 699 human gene clusters, which could define 34 057 (98.1%) protein-coding and 642 (1.9%) non-protein-coding loci; 858 (2.5%) transcribed loci overlapped with predicted pseudogenes. For all these transcripts and genes, we provide comprehensive annotation including gene structures, gene functions, alternative splicing variants, functional non-protein-coding RNAs, functional domains, predicted sub cellular localizations, metabolic pathways, predictions of protein 3D structure, mapping of SNPs and microsatellite repeat motifs, co-localization with orphan diseases, gene expression profiles, orthologous genes, protein-protein interactions (PPI) and annotation for gene families. The current H-InvDB annotation resources consist of two main views: Transcript view and Locus view and eight sub-databases: the DiseaseInfo Viewer, H-ANGEL, the Clustering Viewer, G-integra, the TOPO Viewer, Evola, the PPI view and the Gene family/group.

• H-DBAS: alternative splicing database of completely sequenced and manually annotated full-length cDNAs based on H-Invitational.

  Authors: Jun-ichi Takeda, Yutaka Suzuki, Mitsuteru Nakao, Tsuyoshi Kuroda, Sumio Sugano, Takashi Gojobori, Tadashi Imanishi

  Nucleic acids research. 02/2007; 35(Database issue):D104-9.

  The Human-transcriptome DataBase for Alternative Splicing (H-DBAS) is a specialized database of alternatively spliced human transcripts. In this database, each of the alternative splicing (AS)The Human-transcriptome DataBase for Alternative Splicing (H-DBAS) is a specialized database of alternatively spliced human transcripts. In this database, each of the alternative splicing (AS) variants corresponds to a completely sequenced and carefully annotated human full-length cDNA, one of those collected for the H-Invitational human-transcriptome annotation meeting. H-DBAS contains 38,664 representative alternative splicing variants (RASVs) in 11,744 loci, in total. The data is retrievable by various features of AS, which were annotated according to manual annotations, such as by patterns of ASs, consequently invoked alternations in the encoded amino acids and affected protein motifs, GO terms, predicted subcellular localization signals and transmembrane domains. The database also records recently identified very complex patterns of AS, in which two distinct genes seemed to be bridged, nested or degenerated (multiple CDS): in all three cases, completely unrelated proteins are encoded by a single locus. By using AS Viewer, each AS event can be analyzed in the context of full-length cDNAs, enabling the user's empirical understanding of the relation between AS event and the consequent alternations in the encoded amino acid sequences together with various kinds of affected protein motifs. H-DBAS is accessible at http://jbirc.jbic.or.jp/h-dbas/.

• Large-scale identification and characterization of alternative splicing variants of human gene transcripts using 56 419 completely sequenced and manually annotated full-length cDNAs

  Authors: Jun-Ichi Takeda, Yutaka Suzuki, Mitsuteru Nakao, Roberto A Barrero, Kanako O Koyanagi, Lihua Jin, Chie Motono, Hiroko Hata, Takao Isogai, Keiichi Nagai, Tetsuji Otsuki, Vladimir Kuryshev, Masafumi Shionyu, Stefan Wiemann, Nobuo Nomura, Sumio Sugano, Takashi Gojobori, Tadashi Imanishi

  Nucleic Acids Research. 08/2006; 34:3917--3928.

  We report the first genome-wide identification and characterization of alternative splicing in human gene transcripts based on analysis of the full-length cDNAs. Applying both manual andWe report the first genome-wide identification and characterization of alternative splicing in human gene transcripts based on analysis of the full-length cDNAs. Applying both manual and computational analyses for 56 419 completely sequenced and precisely annotated full-length cDNAs selected for the H-Invitational human transcriptome annotation meetings, we identified 6877 alternative splicing genes with 18 297 different alternative splicing variants. A total of 37 670 exons were involved in these alternative splicing events. The encoded protein sequences were affected in 6005 of the 6877 genes. Notably, alternative splicing affected protein motifs in 3015 genes, subcellular localiza-tions in 2982 genes and transmembrane domains in 1348 genes. We also identified interesting patterns of alternative splicing, in which two distinct genes seemed to be bridged, nested or having overlapping protein coding sequences (CDSs) of different reading:10.1093/nar/gkl507 frames (multiple CDS). In these cases, completely unrelated proteins are encoded by a single locus. Genome-wide annotations of alternative splicing, relying on full-length cDNAs, should lay firm groundwork for exploring in detail the diversifica-tion of protein function, which is mediated by the fast expanding universe of alternative splicing variants. INTRODUCTION

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• Large-scale identification and characterization of alternative splicing variants of human gene transcripts using 56,419 completely sequenced and manually annotated full-length cDNAs.

  Authors: Jun-ichi Takeda, Yutaka Suzuki, Mitsuteru Nakao, Roberto A Barrero, Kanako O Koyanagi, Lihua Jin, Chie Motono, Hiroko Hata, Takao Isogai, Keiichi Nagai [......] Masafumi Shionyu, Kei Yura, Mitiko Go, Jean Thierry-Mieg, Danielle Thierry-Mieg, Stefan Wiemann, Nobuo Nomura, Sumio Sugano, Takashi Gojobori, Tadashi Imanishi

  Nucleic acids research. 02/2006; 34(14):3917-28.

  We report the first genome-wide identification and characterization of alternative splicing in human gene transcripts based on analysis of the full-length cDNAs. Applying both manual andWe report the first genome-wide identification and characterization of alternative splicing in human gene transcripts based on analysis of the full-length cDNAs. Applying both manual and computational analyses for 56,419 completely sequenced and precisely annotated full-length cDNAs selected for the H-Invitational human transcriptome annotation meetings, we identified 6877 alternative splicing genes with 18 297 different alternative splicing variants. A total of 37,670 exons were involved in these alternative splicing events. The encoded protein sequences were affected in 6005 of the 6877 genes. Notably, alternative splicing affected protein motifs in 3015 genes, subcellular localizations in 2982 genes and transmembrane domains in 1348 genes. We also identified interesting patterns of alternative splicing, in which two distinct genes seemed to be bridged, nested or having overlapping protein coding sequences (CDSs) of different reading frames (multiple CDS). In these cases, completely unrelated proteins are encoded by a single locus. Genome-wide annotations of alternative splicing, relying on full-length cDNAs, should lay firm groundwork for exploring in detail the diversification of protein function, which is mediated by the fast expanding universe of alternative splicing variants.

• Large-scale analysis of human alternative protein isoforms: pattern classification and correlation with subcellular localization signals.

  Authors: Mitsuteru Nakao, Roberto A Barrero, Yuri Mukai, Chie Motono, Makiko Suwa, Kenta Nakai

  Nucleic acids research. 01/2005; 33(8):2355-63.

  We investigated human alternative protein isoforms of >2600 genes based on full-length cDNA clones and SwissProt. We classified the isoforms and examined their co-occurrence for each gene. Further,We investigated human alternative protein isoforms of >2600 genes based on full-length cDNA clones and SwissProt. We classified the isoforms and examined their co-occurrence for each gene. Further, we investigated potential relationships between these changes and differential subcellular localization. The two most abundant patterns were the one with different C-terminal regions and the one with an internal insertion, which together account for 43% of the total. Although changes of the N-terminal region are less common than those of the C-terminal region, extension of the C-terminal region is much less common than that of the N-terminal region, probably because of the difficulty of removing stop codons in one isoform. We also found that there are some frequently used combinations of co-occurrence in alternative isoforms. We interpret this as evidence that there is some structural relationship which produces a repertoire of isoformal patterns. Finally, many terminal changes are predicted to cause differential subcellular localization, especially in targeting either peroxisomes or mitochondria. Our study sheds new light on the enrichment of the human proteome through alternative splicing and related events. Our database of alternative protein isoforms is available through the internet.

• 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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• DBTBS: database of transcriptional regulation in Bacillus subtilis and its contribution to comparative genomics.

  Authors: Yuko Makita, Mitsuteru Nakao, Naotake Ogasawara, Kenta Nakai

  Nucleic acids research. 02/2004; 32(Database issue):D75-7.

  DBTBS (http://dbtbs.hgc.jp) was originally released in 1999 as a reference database of published transcriptional regulation events in Bacillus subtilis, one of the best studied bacteria. It isDBTBS (http://dbtbs.hgc.jp) was originally released in 1999 as a reference database of published transcriptional regulation events in Bacillus subtilis, one of the best studied bacteria. It is essentially a compilation of transcription factors with their regulated genes as well as their recognition sequences, which were experimentally characterized and reported in the literature. Here we report its major update, which contains information on 114 transcription factors, including sigma factors, and 633 promoters of 525 genes. The number of references cited in the database has increased from 291 to 378. It also supports a function to find putative transcription factor binding sites within input sequences by using our collection of weight matrices and consensus patterns. Furthermore, though preliminarily, DBTBS now aims to contribute to comparative genomics by showing the presence or absence of potentially orthologous transcription factors and their corresponding cis-elements on the promoters of their potentially orthologously regulated genes in 50 eubacterial genomes.

• 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.

• BTBS: database of transcriptional regulation in Bacillus subtilis and its contribution to comparative genomics.

  Authors: Yuko Makita, Mitsuteru Nakao, Naotake Ogasawara, Kenta Nakai

  Nucleic Acids Research. 01/2004; 32:75-77.

• Quantitative Estimation of Cross-Hybridization in DNA Microarrays Based on a Linear Model

  Authors: Mitsuteru Nakao, Yoshinori K. Okuji, Minoru Kanehisa

  03/2001;

  Introduction Microarraye(q[(J.[) data contains possible esibl that could be classifie into two typ eJone reflW se ting syste]flJ. este andthe othe reeFWF ting random endomJ Syste)[]T eyste mayIntroduction Microarraye(q[(J.[) data contains possible esibl that could be classifie into two typ eJone reflW se ting syste]flJ. este andthe othe reeFWF ting random endomJ Syste)[]T eyste may occurdue todi#e][ t factors such as shape of spots, purity of probeo sebJ))]W of ree[ transcription (RT) primeFfl highe orde structure oftarge nucleWJ.)F and probeobJ)W( cross-hybridization [1, 2]. In this study, we propose alineT mo de ofsysteqJ.) eyste cause by probeobJ[qW cross-hybridization. We eWFq]J. the influe.)W of suchsysteJ.)W eyste so as tore[q]]J.)W more reeq]]J gee req]]J.) ne works and co-e(TWJ.)[F gegroups bythe profile [3]. 2 Method and Results 2.1 Data preparation We use geq eq]J.TW]F profile that weT me]((flJ bythe microarray, CyanoChip [6] by TaKaRa (Kyoto, apan) that contains almost all ORFs, 3079 ORFseFsJ))(q transp inthe Synechocystis sp. PCC6803 ge803 [4].The probe DNAseJTW(OO we) preTFOJ up tothe le(( of 1,000 nt and spotte

• Genome-scale Gene Expression Analysis and Pathway Reconstruction in KEGG

  Authors: Mitsuteru Nakao, Hidemasa Bono, Shuichi Kawashima, Tomomi Kamiya, Kazushige Sato, Minoru Kanehisa

  01/2000;

  The massively parallel hybridization technologies by DNA chips and microarrays make it possible to monitor expression patterns of the whole set of genes in a genome under various conditions. The vastThe massively parallel hybridization technologies by DNA chips and microarrays make it possible to monitor expression patterns of the whole set of genes in a genome under various conditions. The vast amount of data generated by such technologies necessitates the development of a new database management system that integrates expression data with other molecular biology databases and various analysis tools. We report here an extension of our KEGG (Kyoto Encyclopedia of Genes and Genomes) and DBGET/LinkDB systems for analyzing gene expression data in conjunction with pathway information and genomic information. It is now possible to make use of expression data for the reconstruction of pathways from the complete genome sequences. 1