H-InvDB in 2013: an omics study platform for human functional gene and transcript discovery.

H-InvDB (http://www.h-invitational.jp/) is a comprehensive human gene database started in 2004. In the latest version, H-InvDB 8.0, a total of 244 709 human complementary DNA was mapped onto the hg19 reference genome and 43 829 gene loci, including nonprotein-coding ones, were identified. Of these loci, 35 631 were identified as potential protein-coding genes, and 22 898 of these were identical to known genes. In our analysis, 19 309 annotated genes were specific to H-InvDB and not found in RefSeq and Ensembl. In fact, 233 genes of the 19 309 turned out to have protein functions in this version of H-InvDB; they were annotated as unknown protein functions in the previous version. Furthermore, 11 genes were identified as known Mendelian disorder genes. It is advantageous that many biologically functional genes are hidden in the H-InvDB unique genes. As large-scale proteomic projects have been conducted to elucidate the functions of all human proteins, we have enhanced the proteomic information with an advanced protein view and new subdatabase of protein complexes (Protein Complex Database with quality index). We propose that H-InvDB is an important resource for finding novel candidate targets for medical care and drug development.

Full-length transcriptome-based H-InvDB throws a new light on chromosome-centric proteomics.

H-Invitational Database (H-InvDB; http://hinv.jp/ ) is an integrated database of all human genes and transcripts that started in an international collaborative research project for establishing a functional annotation database of human full-length cDNAs. Because H-InvDB contains an abundance of information for human transcripts, including not only well-characterized protein-coding transcripts but also those without experimental evidence at the protein level, this will be a useful information resource for identifying novel and uncharacterized human proteins (so-called missing proteins). By extending predicted protein data in H-InvDB, we developed the H-Inv Extended Protein Database (H-EPD; http://hinv.jp/hinv/h-epd/ ). From now on, we plan to carry out a database-driven proteome research that makes full use of H-EPD to promote discoveries in the current and future C-HPP. Furthermore, we will push forward with the integration of genome, transcriptome, and proteome databases using a unique tool for connecting distributed databases and would like to develop a knowledge discovery system by incorporating data mining tools.

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

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 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.

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

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 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/.

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

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 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/.

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

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 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): hub for Oryza sativa ssp. japonica genome information.

With the completion of the rice genome sequencing, a standardized annotation is necessary so that the information from the genome sequence can be fully utilized in understanding the biology of rice and other cereal crops. An annotation jamboree was held in Japan with the aim of annotating and manually curating all the genes in the rice genome. Here we present the Rice Annotation Project Database (RAP-DB), which has been developed to provide access to the annotation data. The RAP-DB has two different types of annotation viewers, BLAST and BLAT search, and other useful features. By connecting the annotations to other rice genomics data, such as full-length cDNAs and Tos17 mutant lines, the RAP-DB serves as a hub for rice genomics. All of the resources can be accessed through http://rapdb.lab.nig.ac.jp/.

A web tool for comparative genomics: G-compass.

In order to assist the progression of comparative genomics, we have developed a new web-based tool, named G-compass, for browsing and analysis of genome alignments. G-compass utilizes 829,311 pieces of genome alignments between human and mouse that were originally produced for this tool. The quality of the genome alignment set was evaluated by using several statistics. As a result, the alignment set is found to cover approximately 17% of the human genome and 82% of the annotated exons. The averages of nucleotide sequence identity and sequence length are 71.2% and 673.6 bp, respectively. In comparison with public data, it appeared that our data is more expansive and possesses greater genome coverage. G-compass incorporates unique functions such as window analysis of individual alignments. Furthermore, with G-compass and the joint help of H-InvDB, we were able to find highly conserved genomic segments and a human specific antisense transcript candidate, demonstrating that G-compass is useful for facilitating biological discoveries. G-compass is publicly accessible on the WWW at http://www.jbirc.aist.go.jp/g-compass/.

Comparative genome analysis of three eukaryotic parasites with differing abilities to transform leukocytes reveals key mediators of Theileria-induced leukocyte transformation.

We sequenced the genome of Theileria orientalis, a tick-borne apicomplexan protozoan parasite of cattle. The focus of this study was a comparative genome analysis of T. orientalis relative to other highly pathogenic Theileria species, T. parva and T. annulata. T. parva and T. annulata induce transformation of infected cells of lymphocyte or macrophage/monocyte lineages; in contrast, T. orientalis does not induce uncontrolled proliferation of infected leukocytes and multiplies predominantly within infected erythrocytes. While synteny across homologous chromosomes of the three Theileria species was found to be well conserved overall, subtelomeric structures were found to differ substantially, as T. orientalis lacks the large tandemly arrayed subtelomere-encoded variable secreted protein-encoding gene family. Moreover, expansion of particular gene families by gene duplication was found in the genomes of the two transforming Theileria species, most notably, the TashAT/TpHN and Tar/Tpr gene families. Gene families that are present only in T. parva and T. annulata and not in T. orientalis, Babesia bovis, or Plasmodium were also identified. Identification of differences between the genome sequences of Theileria species with different abilities to transform and immortalize bovine leukocytes will provide insight into proteins and mechanisms that have evolved to induce and regulate this process. The T. orientalis genome database is available at http://totdb.czc.hokudai.ac.jp/.

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

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) 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.