Chisato Yamasaki

Publications of Chisato Yamasaki

• A prioritization analysis of disease association by data-mining of functional annotation of human genes.

  Authors: Takayuki Taniya, Susumu Tanaka, Yumi Yamaguchi-Kabata, Hideki Hanaoka, Chisato Yamasaki, Harutoshi Maekawa, Roberto A Barrero, Boris Lenhard, Milton W Datta, Mary Shimoyama, Roger Bumgarner, Ranajit Chakraborty, Ian Hopkinson, Libin Jia, Winston Hide, Charles Auffray, Shinsei Minoshima, Tadashi Imanishi, Takashi Gojobori

  Genomics. 01/2012; 99(1):1-9.

  Complex diseases result from contributions of multiple genes that act in concert through pathways. Here we present a method to prioritize novel candidates of disease-susceptibility genes depending onComplex diseases result from contributions of multiple genes that act in concert through pathways. Here we present a method to prioritize novel candidates of disease-susceptibility genes depending on the biological similarities to the known disease-related genes. The extent of disease-susceptibility of a gene is prioritized by analyzing seven features of human genes captured in H-InvDB. Taking rheumatoid arthritis (RA) and prostate cancer (PC) as two examples, we evaluated the efficiency of our method. Highly scored genes obtained included TNFSF12 and OSM as candidate disease genes for RA and PC, respectively. Subsequent characterization of these genes based upon an extensive literature survey reinforced the validity of these highly scored genes as possible disease-susceptibility genes. Our approach, Prioritization ANalysis of Disease Association (PANDA), is an efficient and cost-effective method to narrow down a large set of genes into smaller subsets that are most likely to be involved in the disease pathogenesis.

• 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.

• CIPRO 2.5:

  Authors: Toshinori Endo, Keisuke Ueno, Kouki Yonezawa, Katsuhiko Mineta, Kohji Hotta, Yutaka Satou, Lixy Yamada, Michio Ogasawara, Hiroki Takahashi, Ayako Nakajima, Mia Nakachi, Mamoru Nomura, Junko Yaguchi, Yasunori Sasakura, Chisato Yamasaki, Miho Sera, Akiyasu C. Yoshizawa, Tadashi Imanishi, Hisaaki Taniguchi, Kazuo Inaba

  Nucleic Acids Research. 01/2011; 39:807-814.

• Towards BioDBcore: a community-defined information specification for biological databases.

  Authors: Pascale Gaudet, Amos Bairoch, Dawn Field, Susanna-Assunta Sansone, Chris F. Taylor, Teresa K. Attwood, Alex Bateman, Judith A. Blake, Carol J. Bult, J. Michael Cherry [......] Lorna Richardson, Philippe Rocca-Serra, Paul N. Schofield, Damian Smedley, Christopher Southan, Tin Wee Tan, Tatiana A. Tatusova, Patricia L. Whetzel, Owen White, Chisato Yamasaki

  Nucleic Acids Research. 01/2011; 39:7-10.

• Towards BioDBcore: a community-defined information specification for biological databases.

  Authors: Pascale Gaudet, Amos Bairoch, Dawn Field, Susanna-Assunta Sansone, Chris Taylor, Teresa K Attwood, Alex Bateman, Judith A Blake, Carol J Bult, J Michael Cherry [......] Lorna Richardson, Philippe Rocca-Serra, Paul N Schofield, Damian Smedley, Christopher Southan, Tin Wee Tan, Tatiana Tatusova, Patricia L Whetzel, Owen White, Chisato Yamasaki

  Nucleic acids research. 01/2011; 39(Database issue):D7-10.

  The present article proposes the adoption of a community-defined, uniform, generic description of the core attributes of biological databases, BioDBCore. The goals of these attributes are to provideThe present article proposes the adoption of a community-defined, uniform, generic description of the core attributes of biological databases, BioDBCore. The goals of these attributes are to provide a general overview of the database landscape, to encourage consistency and interoperability between resources and to promote the use of semantic and syntactic standards. BioDBCore will make it easier for users to evaluate the scope and relevance of available resources. This new resource will increase the collective impact of the information present in biological databases.

• CIPRO 2.5: Ciona intestinalis protein database, a unique integrated repository of large-scale omics data, bioinformatic analyses and curated annotation, with user rating and reviewing functionality.

  Authors: Toshinori Endo, Keisuke Ueno, Kouki Yonezawa, Katsuhiko Mineta, Kohji Hotta, Yutaka Satou, Lixy Yamada, Michio Ogasawara, Hiroki Takahashi, Ayako Nakajima, Mia Nakachi, Mamoru Nomura, Junko Yaguchi, Yasunori Sasakura, Chisato Yamasaki, Miho Sera, Akiyasu C Yoshizawa, Tadashi Imanishi, Hisaaki Taniguchi, Kazuo Inaba

  Nucleic acids research. 11/2010; 39(Database issue):D807-14.

  The Ciona intestinalis protein database (CIPRO) is an integrated protein database for the tunicate species C. intestinalis. The database is unique in two respects: first, because of its phylogeneticThe Ciona intestinalis protein database (CIPRO) is an integrated protein database for the tunicate species C. intestinalis. The database is unique in two respects: first, because of its phylogenetic position, Ciona is suitable model for understanding vertebrate evolution; and second, the database includes original large-scale transcriptomic and proteomic data. Ciona intestinalis has also been a favorite of developmental biologists. Therefore, large amounts of data exist on its development and morphology, along with a recent genome sequence and gene expression data. The CIPRO database is aimed at collecting those published data as well as providing unique information from unpublished experimental data, such as 3D expression profiling, 2D-PAGE and mass spectrometry-based large-scale analyses at various developmental stages, curated annotation data and various bioinformatic data, to facilitate research in diverse areas, including developmental, comparative and evolutionary biology. For medical and evolutionary research, homologs in humans and major model organisms are intentionally included. The current database is based on a recently developed KH model containing 36,034 unique sequences, but for higher usability it covers 89,683 all known and predicted proteins from all gene models for this species. Of these sequences, more than 10,000 proteins have been manually annotated. Furthermore, to establish a community-supported protein database, these annotations are open to evaluation by users through the CIPRO website. CIPRO 2.5 is freely accessible at http://cipro.ibio.jp/2.5.

• H-InvDB in 2009: extended database and data mining resources for human genes and transcripts.

  Authors: Chisato Yamasaki, Katsuhiko Murakami, Jun-ichi Takeda, Yoshiharu Sato, Akiko Noda, Ryuichi Sakate, Takuya Habara, Hajime Nakaoka, Fusano Todokoro, Akihiro Matsuya, Tadashi Imanishi, Takashi Gojobori

  Nucleic acids research. 11/2009;

  We report the extended database and data mining resources newly released in the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). H-InvDB is a comprehensive annotation resource ofWe report the extended database and data mining resources newly released in the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). H-InvDB is a comprehensive annotation resource of human genes and transcripts, and consists of two main views and six sub-databases. The latest release of H-InvDB (release 6.2) provides the annotation for 219 765 human transcripts in 43 159 human gene clusters based on human full-length cDNAs and mRNAs. H-InvDB now provides several new annotation features, such as mapping of microarray probes, new gene models, relation to known ncRNAs and information from the Glycogene database. H-InvDB also provides useful data mining resources-'Navigation search', 'H-InvDB Enrichment Analysis Tool (HEAT)' and web service APIs. 'Navigation search' is an extended search system that enables complicated searches by combining 16 different search options. HEAT is a data mining tool for automatically identifying features specific to a given human gene set. HEAT searches for H-InvDB annotations that are significantly enriched in a user-defined gene set, as compared with the entire H-InvDB representative transcripts. H-InvDB now has web service APIs of SOAP and REST to allow the use of H-InvDB data in programs, providing the users extended data accessibility.

• VarySysDB: a human genetic polymorphism database based on all H-InvDB transcripts.

  Authors: Makoto K Shimada, Ryuzou Matsumoto, Yosuke Hayakawa, Ryoko Sanbonmatsu, Craig Gough, Yumi Yamaguchi-Kabata, Chisato Yamasaki, Tadashi Imanishi, Takashi Gojobori

  Nucleic acids research. 11/2008;

  Creation of a vast variety of proteins is accomplished by genetic variation and a variety of alternative splicing transcripts. Currently, however, the abundant available data on genetic variation andCreation of a vast variety of proteins is accomplished by genetic variation and a variety of alternative splicing transcripts. Currently, however, the abundant available data on genetic variation and the transcriptome are stored independently and in a dispersed fashion. In order to provide a research resource regarding the effects of human genetic polymorphism on various transcripts, we developed VarySysDB, a genetic polymorphism database based on 187 156 extensively annotated matured mRNA transcripts from 36 073 loci provided by H-InvDB. VarySysDB offers information encompassing published human genetic polymorphisms for each of these transcripts separately. This allows comparisons of effects derived from a polymorphism on different transcripts. The published information we analyzed includes single nucleotide polymorphisms and deletion-insertion polymorphisms from dbSNP, copy number variations from Database of Genomic Variants, short tandem repeats and single amino acid repeats from H-InvDB and linkage disequilibrium regions from D-HaploDB. The information can be searched and retrieved by features, functions and effects of polymorphisms, as well as by keywords. VarySysDB combines two kinds of viewers, GBrowse and Sequence View, to facilitate understanding of the positional relationship among polymorphisms, genome, transcripts, loci and functional domains. We expect that VarySysDB will yield useful information on polymorphisms affecting gene expression and phenotypes. VarySysDB is available at http://h-invitational.jp/varygene/.

• 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.

• The Rice Annotation Project Database (RAP-DB): 2008 update.

  Authors: Tsuyoshi Tanaka, Baltazar A Antonio, Shoshi Kikuchi, Takashi Matsumoto, Yoshiaki Nagamura, Hisataka Numa, Hiroaki Sakai, Jianzhong Wu, Takeshi Itoh, Takuji Sasaki [......] Andrea Zuccolo, Rod A Wing, Kan Nobuta, Pamela J Green, Cheng Lu, Blake C Meyers, Cristian Chaparro, Benoit Piegu, Olivier Panaud, Manuel Echeverria

  Nucleic acids research. 02/2008; 36(Database issue):D1028-33.

  The Rice Annotation Project Database (RAP-DB) was created to provide the genome sequence assembly of the International Rice Genome Sequencing Project (IRGSP), manually curated annotation of theThe Rice Annotation Project Database (RAP-DB) was created to provide the genome sequence assembly of the International Rice Genome Sequencing Project (IRGSP), manually curated annotation of the sequence, and other genomics information that could be useful for comprehensive understanding of the rice biology. Since the last publication of the RAP-DB, the IRGSP genome has been revised and reassembled. In addition, a large number of rice-expressed sequence tags have been released, and functional genomics resources have been produced worldwide. Thus, we have thoroughly updated our genome annotation by manual curation of all the functional descriptions of rice genes. The latest version of the RAP-DB contains a variety of annotation data as follows: clone positions, structures and functions of 31 439 genes validated by cDNAs, RNA genes detected by massively parallel signature sequencing (MPSS) technology and sequence similarity, flanking sequences of mutant lines, transposable elements, etc. Other annotation data such as Gnomon can be displayed along with those of RAP for comparison. We have also developed a new keyword search system to allow the user to access useful information. The RAP-DB is available at: http://rapdb.dna.affrc.go.jp/ and http://rapdb.lab.nig.ac.jp/.

• Evola: Ortholog database of all human genes in H-InvDB with manual curation of phylogenetic trees.

  Authors: Akihiro Matsuya, Ryuichi Sakate, Yoshihiro Kawahara, Kanako O Koyanagi, Yoshiharu Sato, Yasuyuki Fujii, Chisato Yamasaki, Takuya Habara, Hajime Nakaoka, Fusano Todokoro [......] Katsuhiko Murakami, Akiko Ogura Noda, Naomi Saichi, Ryoko Sanbonmatsu, Mami Suzuki, Jun-ichi Takeda, Masayuki Tanaka, Takashi Gojobori, Tadashi Imanishi, Takeshi Itoh

  Nucleic acids research. 02/2008; 36(Database issue):D787-92.

  Orthologs are genes in different species that evolved from a common ancestral gene by speciation. Currently, with the rapid growth of transcriptome data of various species, more reliable orthologyOrthologs are genes in different species that evolved from a common ancestral gene by speciation. Currently, with the rapid growth of transcriptome data of various species, more reliable orthology information is prerequisite for further studies. However, detection of orthologs could be erroneous if pairwise distance-based methods, such as reciprocal BLAST searches, are utilized. Thus, as a sub-database of H-InvDB, an integrated database of annotated human genes (http://h-invitational.jp/), we constructed a fully curated database of evolutionary features of human genes, called 'Evola'. In the process of the ortholog detection, computational analysis based on conserved genome synteny and transcript sequence similarity was followed by manual curation by researchers examining phylogenetic trees. In total, 18 968 human genes have orthologs among 11 vertebrates (chimpanzee, mouse, cow, chicken, zebrafish, etc.), either computationally detected or manually curated orthologs. Evola provides amino acid sequence alignments and phylogenetic trees of orthologs and homologs. In 'd(N)/d(S) view', natural selection on genes can be analyzed between human and other species. In 'Locus maps', all transcript variants and their exon/intron structures can be compared among orthologous gene loci. We expect the Evola to serve as a comprehensive and reliable database to be utilized in comparative analyses for obtaining new knowledge about human genes. Evola is available at http://www.h-invitational.jp/evola/.

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• Curated genome annotation of Oryza sativa ssp. japonica and comparative genome analysis with Arabidopsis thaliana.

  Authors: Takeshi Itoh, Tsuyoshi Tanaka, Roberto A Barrero, Chisato Yamasaki, Yasuyuki Fujii, Phillip B. Hilton, Baltazar A Antonio, Hideo Aono, Rolf Apweiler, Richard Bruskiewich [......] Kaori Yamaguchi, Mayu Yamamoto, Naoyuki Yamamoto, Yeisoo Yu, Hao Zhang, Qiang Zhao, Kenichi Higo, Benjamin Burr, Takashi Gojobori, Takuji Sasaki

  Genome research. 03/2007; 17(2):175-83.

  We present here the annotation of the complete genome of rice Oryza sativa L. ssp. japonica cultivar Nipponbare. All functional annotations for proteins and non-protein-coding RNA (npRNA) candidatesWe present here the annotation of the complete genome of rice Oryza sativa L. ssp. japonica cultivar Nipponbare. All functional annotations for proteins and non-protein-coding RNA (npRNA) candidates were manually curated. Functions were identified or inferred in 19,969 (70%) of the proteins, and 131 possible npRNAs (including 58 antisense transcripts) were found. Almost 5000 annotated protein-coding genes were found to be disrupted in insertional mutant lines, which will accelerate future experimental validation of the annotations. The rice loci were determined by using cDNA sequences obtained from rice and other representative cereals. Our conservative estimate based on these loci and an extrapolation suggested that the gene number of rice is approximately 32,000, which is smaller than previous estimates. We conducted comparative analyses between rice and Arabidopsis thaliana and found that both genomes possessed several lineage-specific genes, which might account for the observed differences between these species, while they had similar sets of predicted functional domains among the protein sequences. A system to control translational efficiency seems to be conserved across large evolutionary distances. Moreover, the evolutionary process of protein-coding genes was examined. Our results suggest that natural selection may have played a role for duplicated genes in both species, so that duplication was suppressed or favored in a manner that depended on the function of a gene.

• TACT: Transcriptome Auto-annotation Conducting Tool of H-InvDB.

  Authors: Chisato Yamasaki, Hiroaki Kawashima, Fusano Todokoro, Yasuhiro Imamizu, Makoto Ogawa, Motohiko Tanino, Takeshi Itoh, Takashi Gojobori, Tadashi Imanishi

  Nucleic acids research. 08/2006; 34(Web Server issue):W345-9.

  Transcriptome Auto-annotation Conducting Tool (TACT) is a newly developed web-based automated tool for conducting functional annotation of transcripts by the integration of sequence similarityTranscriptome Auto-annotation Conducting Tool (TACT) is a newly developed web-based automated tool for conducting functional annotation of transcripts by the integration of sequence similarity searches and functional motif predictions. We developed the TACT system by integrating two kinds of similarity searches, FASTY and BLASTX, against protein sequence databases, UniProtKB (Swiss-Prot/TrEMBL) and RefSeq, and a unified motif prediction program, InterProScan, into the ORF-prediction pipeline originally designed for the 'H-Invitational' human transcriptome annotation project. This system successively applies these constituent programs to an mRNA sequence in order to predict the most plausible ORF and the function of the protein encoded. In this study, we applied the TACT system to 19 574 non-redundant human transcripts registered in H-InvDB and evaluated its predictive power by the degree of agreement with human-curated functional annotation in H-InvDB. As a result, the TACT system could assign functional description to 12 559 transcripts (64.2%), the remainder being hypothetical proteins. Furthermore, the overall agreement of functional annotation with H-InvDB, including those transcripts annotated as hypothetical proteins, was 83.9% (16 432/19 574). These results show that the TACT system is useful for functional annotation and that the prediction of ORFs and protein functions is highly accurate and close to the results of human curation. TACT is freely available at http://www.jbirc.aist.go.jp/tact/.

• Investigation of protein functions through data-mining on integrated human transcriptome database, H-Invitational database (H-InvDB).

  Authors: Chisato Yamasaki, Kanako O Koyanagi, Yasuyuki Fujii, Takeshi Itoh, Roberto Barrero, Takuro Tamura, Yumi Yamaguchi-Kabata, Motohiko Tanino, Jun-ichi Takeda, Satoshi Fukuchi, Satoru Miyazaki, Nobuo Nomura, Sumio Sugano, Tadashi Imanishi, Takashi Gojobori

  Gene. 01/2006; 364:99-107.

  H-Invitational Database (H-InvDB; ) is a human transcriptome database, containing integrative annotation of 41,118 full-length cDNA clones originated from 21,037 loci. H-InvDB is a product of theH-Invitational Database (H-InvDB; ) is a human transcriptome database, containing integrative annotation of 41,118 full-length cDNA clones originated from 21,037 loci. H-InvDB is a product of the H-Invitational project, an international collaboration to systematically and functionally validate human genes by analysis of a unique set of high quality full-length cDNA clones using automatic annotation and human curation under unified criteria. Here, 19,574 proteins encoded by these cDNAs were classified into 11,709 function-known and 7865 function-unknown hypothetical proteins by similarity with protein databases and motif prediction (InterProScan). The proportion of "hypothetical proteins" in H-InvDB was as high as 40.4%. In this study, we thus conducted data-mining in H-InvDB with the aim of assigning advanced functional annotations to those hypothetical proteins. First, by data-mining in the H-InvDB version of GTOP, we identified 337 SCOP domains within 7865 H-Inv hypothetical proteins. Second, by data-mining of predicted subcellular localization by SOSUI and TMHMM in H-InvDB, we found 1032 transmembrane proteins within H-Inv hypothetical proteins. These results clearly demonstrate that structural prediction is effective for functional annotation of proteins with unknown functions. All the data in H-InvDB are shown in two main views, the cDNA view and the Locus view, and five auxiliary databases with web-based viewers; DiseaseInfo Viewer, H-ANGEL, Clustering Viewer, G-integra and TOPO Viewer; the data also are provided as flat files and XML files. The data consists of descriptions of their gene structures, novel alternative splicing isoforms, functional RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein 3D structure, mapping of SNPs and microsatellite repeat motifs in relation with orphan diseases, gene expression profiling, and comparisons with mouse full-length cDNAs in the context of molecular evolution. This unique integrative platform for conducting in silico data-mining represents a substantial contribution to resources required for the exploration of human biology and pathology.

• Genome Informatics 14: 454--455 (2003) Improvement in the Accuracy of Gene Prediction in

  Authors: Fusano Todokoro, Takeshi Itoh, Chisato Yamasaki, Hiroaki Kawashima, Tadashi Imanishi, Takashi Gojobori

  07/2004;

  Introduction GeneMark is a gene prediction program which has been designed to predict prokaryotic genes [2]. In addition the program may be used to search for eukaryotic genes in cDNA sequences andIntroduction GeneMark is a gene prediction program which has been designed to predict prokaryotic genes [2]. In addition the program may be used to search for eukaryotic genes in cDNA sequences and also to locate errors in sequence such as frame shifts. The program bases its calculations for gene prediction on a set of standard training data. Eukaryotic genes are predicted by using a separate module for the program which requires matrices based on coding and non-coding regions of sequences from training data [3]. In this study, we investigated the e#ect of varying the GC content of the training data on matrix preparation and in turn its e#ects on the accuracy of gene prediction in human cDNA sequences. 2 Method and Results 2.1 Dataset We obtained 9,657 human cDNA sequences from the DDBJ and calculated the GC content of the each cDNA. Among them, 4,829 cDNA sequences were used as a standard training dataset described in 2.2. The remaining 4,828 cDNA sequences were used for gene pre

• 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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• Induction of cytokines by toxins that have an identical RNA N-glycosidase activity: Shiga toxin, ricin, and modeccin.

  Authors: Chisato Yamasaki, Kiyotaka Nishikawa, Xun-Ting Zeng, Yukie Katayama, Yumiko Natori, Nobukazu Komatsu, Tatsuya Oda, Yasuhiro Natori

  Biochimica et biophysica acta. 04/2004; 1671(1-3):44-50.

  Shiga toxin (Stx) has an A1-B5 subunit structure, and the A subunit is an RNA N-glycosidase that inhibits cellular protein synthesis. We previously reported that in Caco-2 cells Stx induced cytokinesShiga toxin (Stx) has an A1-B5 subunit structure, and the A subunit is an RNA N-glycosidase that inhibits cellular protein synthesis. We previously reported that in Caco-2 cells Stx induced cytokines and that the RNA N-glycosidase activity was essential for the cytokine induction. It is known that the binding of the Stx-B subunit to its receptor glycolipid, Gb3, mediates an A subunit-independent signal in some types of cells, but the involvement of this signal in the cytokine induction is unclear. In this study, we investigated whether RNA N-glycosidase itself induces cytokines. IL-8 production was enhanced by Stx, ricin, and modeccin, three toxins that inhibit protein synthesis through an identical RNA N-glycosidase activity, but not by two other types of protein synthesis inhibitors, diphtheria toxin and cycloheximide. The RNA N-glycosidase-type toxins showed a similar induction pattern of cytokine mRNAs. Brefeldin A, a Golgi apparatus inhibitor, completely suppressed the cytokine induction by the toxins. Analysis by using inhibitors of toxin binding and also Stx-B subunit showed that the cytokine-inducing activity was independent of Gb3-mediated signaling. These results indicate that RNA N-glycosidase itself induces the cytokine production and that intracellular transport of toxins through the Golgi apparatus is essential for the activity.

• 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 therapeutic agent with oriented carbohydrates for treatment of infections by Shiga toxin-producing Escherichia coli O157:H7.

  Authors: Kiyotaka Nishikawa, Koji Matsuoka, Eiji Kita, Noriko Okabe, Masashi Mizuguchi, Kumiko Hino, Shinobu Miyazawa, Chisato Yamasaki, Junken Aoki, Sachio Takashima, Yoshio Yamakawa, Masahiro Nishijima, Daiyo Terunuma, Hiroyoshi Kuzuhara, Yasuhiro Natori

  Proceedings of the National Academy of Sciences of the United States of America. 06/2002; 99(11):7669-74.

  Infection with Shiga toxin (Stx)-producing Escherichia coli O157:H7, which causes diarrhea and hemorrhagic colitis in humans, often results in fatal systemic complications, such as neurologicalInfection with Shiga toxin (Stx)-producing Escherichia coli O157:H7, which causes diarrhea and hemorrhagic colitis in humans, often results in fatal systemic complications, such as neurological damage and hemolytic-uremic syndrome. Because Stx circulating in the blood is a major causative factor of these complications, the development of a Stx neutralizer that functions in the circulation holds promise as a viable therapy. Here we developed a series of carbosilane dendrimers, in which trisaccharides of globotriaosyl ceramide, a receptor for Stx, were variously oriented at their termini (referred to as SUPER TWIG), and identified a SUPER TWIG with six trisaccharides as a Stx neutralizer functioning in the circulation. This SUPER TWIG specifically bound to Stx with high affinity (K(d) = 1.1 x 10(-6) M) and inhibited the incorporation of the toxin into target cells. Intravenous administration of the SUPER TWIG along with Stx to mice substantially reduced the fatal brain damage and completely suppressed the lethal effect of Stx. Moreover, the SUPER TWIG protected mice from challenge with a fatal dose of E. coli O157:H7, even when administered after the establishment of the infection. The SUPER TWIG neutralized Stx in vivo by a mechanism in which the accumulation and immediate degradation of Stx by phagocytic macrophages present in the reticuloendothelial system were induced. Taken together, our findings indicate that this SUPER TWIG is therapeutic agent against infections by Stx-producing E. coli.

• H-InvDB release 6, a comprehensive annotation resource for human genes and transcripts

  Authors: Chisato Yamasaki, Katsuhiko Murakami, Jun-ichi Takeda, Yoshiharu Sato, Akiko Noda, Ryuichi Sakate, Takuya Habara, Hajime Nakaoka, Fusano Todokoro, Akihiro Matsuya, Tadashi Imanishi, Takashi Gojobori

  Nature Precedings.

  H-Invitational Database (H-InvDB; "http://www.h-invitational.jp/":http://www.h-invitational.jp/) is an integrated database of human genes and transcripts. By extensive analyses of all humanH-Invitational Database (H-InvDB; "http://www.h-invitational.jp/":http://www.h-invitational.jp/) is an integrated database of human genes and transcripts. By extensive analyses of all human transcripts, we provide curated annotations of human genes and transcripts that include gene structures, alternative splicing isoforms, non-coding functional RNAs, protein functions, functional domains, sub-cellular localizations, metabolic pathways, protein 3D structure, genetic polymorphisms, relation with diseases, gene expression profiling, molecular evolutionary features, protein-protein interactions (PPIs) and gene families/groups. The latest release of H-InvDB (release 6.0) provide annotation for 219,765 human transcripts in 43,159 human gene clusters based on human FLcDNAs and mRNAs. H-InvDB consists of two main views, the Transcript view and the Locus view, and six auxiliary databases with web-based viewers; G-integra, H-ANGEL, DiseaseInfo Viewer, Evola, PPI view and Gene Family/Group view. We also provides several data mining tools such as “Navi search”: consists of 16 search contents each of which includes items for the search condition ("http://www.h-invitational.jp/hinv/c-search/hinvNaviTop.jsp":http://www.h-invitational.jp/hinv/c-search/hinvNaviTop.jsp), “PANDA”: Priority ANalysis for Disease Association (PANDA) system ("http://www.h-invitational.jp/panda/app":http://www.h-invitational.jp/panda/app), H-InvDB now provides web service APIs of SOAP and REST to use H-InvDB data in programs. ("http://www.h-invitational.jp/hinv/hws/doc/":http://www.h-invitational.jp/hinv/hws/doc/)