DNA Data Bank of Japan: 30th anniversary.

The DNA Data Bank of Japan (DDBJ) Center (http://www.ddbj.nig.ac.jp) has been providing public data services for 30 years since 1987. We are collecting nucleotide sequence data and associated biological information from researchers as a member of the International Nucleotide Sequence Database Collaboration (INSDC), in collaboration with the US National Center for Biotechnology Information and the European Bioinformatics Institute. The DDBJ Center also services the Japanese Genotype-phenotype Archive (JGA) with the National Bioscience Database Center to collect genotype and phenotype data of human individuals. Here, we outline our database activities for INSDC and JGA over the past year, and introduce submission, retrieval and analysis services running on our supercomputer system and their recent developments. Furthermore, we highlight our responses to the amended Japanese rules for the protection of personal information and the launch of the DDBJ Group Cloud service for sharing pre-publication data among research groups.

DNA Data Bank of Japan.

The DNA Data Bank of Japan (DDBJ) (http://www.ddbj.nig.ac.jp) has been providing public data services for thirty years (since 1987). We are collecting nucleotide sequence data from researchers as a member of the International Nucleotide Sequence Database Collaboration (INSDC, http://www.insdc.org), in collaboration with the US National Center for Biotechnology Information (NCBI) and European Bioinformatics Institute (EBI). The DDBJ Center also services Japanese Genotype-phenotype Archive (JGA), with the National Bioscience Database Center to collect human-subjected data from Japanese researchers. Here, we report our database activities for INSDC and JGA over the past year, and introduce retrieval and analytical services running on our supercomputer system and their recent modifications. Furthermore, with the Database Center for Life Science, the DDBJ Center improves semantic web technologies to integrate and to share biological data, for providing the RDF version of the sequence data.

DNA data bank of Japan (DDBJ) progress report.

The DNA Data Bank of Japan Center (DDBJ Center; http://www.ddbj.nig.ac.jp) maintains and provides public archival, retrieval and analytical services for biological information. The contents of the DDBJ databases are shared with the US National Center for Biotechnology Information (NCBI) and the European Bioinformatics Institute (EBI) within the framework of the International Nucleotide Sequence Database Collaboration (INSDC). Since 2013, the DDBJ Center has been operating the Japanese Genotype-phenotype Archive (JGA) in collaboration with the National Bioscience Database Center (NBDC) in Japan. In addition, the DDBJ Center develops semantic web technologies for data integration and sharing in collaboration with the Database Center for Life Science (DBCLS) in Japan. This paper briefly reports on the activities of the DDBJ Center over the past year including submissions to databases and improvements in our services for data retrieval, analysis, and integration.

The DDBJ Japanese Genotype-phenotype Archive for genetic and phenotypic human data.

The DNA Data Bank of Japan Center (DDBJ Center; http://www.ddbj.nig.ac.jp) maintains and provides public archival, retrieval and analytical services for biological information. Since October 2013, DDBJ Center has operated the Japanese Genotype-phenotype Archive (JGA) in collaboration with our partner institute, the National Bioscience Database Center (NBDC) of the Japan Science and Technology Agency. DDBJ Center provides the JGA database system which securely stores genotype and phenotype data collected from individuals whose consent agreements authorize data release only for specific research use. NBDC has established guidelines and policies for sharing human-derived data and reviews data submission and usage requests from researchers. In addition to the JGA project, DDBJ Center develops Semantic Web technologies for data integration and sharing in collaboration with the Database Center for Life Science. This paper describes the overview of the JGA project, updates to the DDBJ databases, and services for data retrieval, analysis and integration.

DDBJ progress report: a new submission system for leading to a correct annotation.

The DNA Data Bank of Japan (DDBJ; http://www.ddbj.nig.ac.jp) maintains and provides archival, retrieval and analytical resources for biological information. This database content is shared with the US National Center for Biotechnology Information (NCBI) and the European Bioinformatics Institute (EBI) within the framework of the International Nucleotide Sequence Database Collaboration (INSDC). DDBJ launched a new nucleotide sequence submission system for receiving traditional nucleotide sequence. We expect that the new submission system will be useful for many submitters to input accurate annotation and reduce the time needed for data input. In addition, DDBJ has started a new service, the Japanese Genotype-phenotype Archive (JGA), with our partner institute, the National Bioscience Database Center (NBDC). JGA permanently archives and shares all types of individual human genetic and phenotypic data. We also introduce improvements in the DDBJ services and databases made during the past year.

DDBJ read annotation pipeline: a cloud computing-based pipeline for high-throughput analysis of next-generation sequencing data.

High-performance next-generation sequencing (NGS) technologies are advancing genomics and molecular biological research. However, the immense amount of sequence data requires computational skills and suitable hardware resources that are a challenge to molecular biologists. The DNA Data Bank of Japan (DDBJ) of the National Institute of Genetics (NIG) has initiated a cloud computing-based analytical pipeline, the DDBJ Read Annotation Pipeline (DDBJ Pipeline), for a high-throughput annotation of NGS reads. The DDBJ Pipeline offers a user-friendly graphical web interface and processes massive NGS datasets using decentralized processing by NIG supercomputers currently free of charge. The proposed pipeline consists of two analysis components: basic analysis for reference genome mapping and de novo assembly and subsequent high-level analysis of structural and functional annotations. Users may smoothly switch between the two components in the pipeline, facilitating web-based operations on a supercomputer for high-throughput data analysis. Moreover, public NGS reads of the DDBJ Sequence Read Archive located on the same supercomputer can be imported into the pipeline through the input of only an accession number. This proposed pipeline will facilitate research by utilizing unified analytical workflows applied to the NGS data. The DDBJ Pipeline is accessible at http://p.ddbj.nig.ac.jp/.

DDBJ new system and service refactoring.

The DNA data bank of Japan (DDBJ, http://www.ddbj.nig.ac.jp) maintains a primary nucleotide sequence database and provides analytical resources for biological information to researchers. This database content is exchanged with the US National Center for Biotechnology Information (NCBI) and the European Bioinformatics Institute (EBI) within the framework of the International Nucleotide Sequence Database Collaboration (INSDC). Resources provided by the DDBJ include traditional nucleotide sequence data released in the form of 27 316 452 entries or 16 876 791 557 base pairs (as of June 2012), and raw reads of new generation sequencers in the sequence read archive (SRA). A Japanese researcher published his own genome sequence via DDBJ-SRA on 31 July 2012. To cope with the ongoing genomic data deluge, in March 2012, our computer previous system was totally replaced by a commodity cluster-based system that boasts 122.5 TFlops of CPU capacity and 5 PB of storage space. During this upgrade, it was considered crucial to replace and refactor substantial portions of the DDBJ software systems as well. As a result of the replacement process, which took more than 2 years to perform, we have achieved significant improvements in system performance.

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

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 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.

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 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.

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 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.

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 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.

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 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-L'EXPO: a tool to extract knowledge From transcriptomes and find 'Literature-Sparse' relationships between genes and tissues.

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 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.

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

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 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.

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 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.

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 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.

Quantification of gene expression in mouse and human renal proximal tubules.

The kidney consists of many functional modules called nephrons. Each nephron has a tubular structure made up of several structurally and functionally distinct segments. The analysis of individual segments requires the use of microdissection techniques. We describe protocols that have been used to successfully isolate messenger RNA from proximal tubules of both freshly prepared and archival samples using laser capture microdissection and laser-manipulated microdissection.