Food safety and epidemiology: new database of functional food factors

More than 600 functional non-nutrient food factors (FFFs) in vegetables and fruits are considered to be effective for health promotion and disease prevention. However, phytochemicals studied thus far have failed to yield predicted results in randomized intervention studies. To assess the health effects of phytochemicals, a breakthrough in epidemiological methods was necessary. We constructed a database of non-nutrient FFFs to estimate the chemical classes and total amount of FFF-intake in order to facilitate estimation and calculation for nutritional research. So far, flavonoids, terpenoids, carotenoids, and sulfur compounds are included in our FFF database. We calculated the intake of various phytochemicals per capita from 79 subjects' dietary records by FFF database, and estimated that subjects ingested more than 10 micromole per day of phytochemicals such as catechin, isoflavones, isothiocyanate, ferulic acid, quercetin, cinnamic acid and chlorogenic acid. Chief component analysis yielded 12 factors (80%), of which only a few factors showed negative associations with serum cholesterol and LDL concentration. Many factors showed adverse relationships with liver function and serum triacylglycerol concentration. Weekly self-reported daily dietary records including name of dish, constituent foods and their amounts were separately collected for 6 months and analyzed in Kyoto women. Seasonal changes of phytochemical intake showed significant variation according to the seasonal consumption of fruits and vegetables. Lycopene increased in the summer due to watermelon and tomato intake in this season. Seasonal variation of FFF was quite large compared to the variation of macro- and micronutrients. Careful evaluation of the effects of FFF intake on health is necessary, especially when supplements are also consumed. The most effective combinations of FFF intake for human health could be elucidated by using our FFF-DB in conjunction with population-based cohort studies.     

RIBDB: an SRS based infrastructure for REALIS

The REALIS project is an EU-funded consortium for the post genomic analysis of the food pathogen Listeria monocytogenes. The data generated by the consortium members is stored under the RIBDB database, a system built using SRS which integrates consortium data, public databases, and applications for analysis. RIBDB is available to all consortium members through a web server, with the option of installing a local mirror of the main server for local analysis.     

High performance web server architecture with Kernel-level caching

In this work we are focusing on reducing response time and bandwidth requirements for high performance web server. Many researches have been done in order to improve web server performance by modifying the web server architecture. In contrast to these approaches, we take a different point of view, in which we consider the web server performance in OS perspective rather than web server architecture itself. To achieve these purposes we are exploring two different approaches. The first is running web server within OS kernel. We use kHTTPd as our basis for implementation. But it has a several drawbacks such as copying data redundantly, synchronous write, and processing only static data. We propose some techniques to improve these flaws. The second approach is caching dynamic data. Dynamic data can seriously reduce the performance of web servers. Caching dynamic data has been thought difficult to cache because it often change a lot more frequently than static pages and because web server needs to access database to provide service with dynamic data. To this end, we propose a solution for higher performance web service by caching dynamic data using content separation between static and dynamic portions. Benchmark results using WebStone show that our architecture can improve server performance by up to 18 percent and can reduce user’s perceived latency significantly.     

A web application to manage a database for liquid nitrogen tanks

Summary We have developed a software, Cell Database, for archiving records about cells stored in liquid nitrogen tanks. Once installed on a web server, the database is accessed through a standard web browser. This user-friendly and self-explanatory application is independent of computer platform and periodic upgrades of a commercial software. Our web application allows import of data from other database programs and adaptation to different tank formats, types of samples, and archiving needs.     

REGANOR

With >1,000 prokaryotic genome sequencing projects ongoing or already finished, comprehensive comparative analysis of the gene content of these genomes has become viable. To allow for a meaningful comparative analysis, gene prediction of the various genomes should be as accurate as possible. It is clear that improving the state of genome annotation requires automated gene identification methods to cope with the influence of artifacts, such as genomic GC content. There is currently still room for improvement in the state of annotations. We present a web server and a database of high-quality gene predictions. The web server is a resource for gene identification in prokaryote genome sequences. It implements our previously described, accurate gene finding method REGANOR. We also provide novel gene predictions for 241 complete, or almost complete, prokaryotic genomes. We demonstrate how this resource can easily be utilised to identify promising candidates for currently missing genes from genome annotations with several examples. All data sets are available online. AVAILABILITY: The gene finding server is accessible via https://www.cebitec.uni-bielefeld.de/groups/brf/software/reganor/cgi-bin/reganor_upload.cgi. The server software is available with the GenDB genome annotation system (version 2.2.1 onwards) under the GNU general public license. The software can be downloaded from https://sourceforge.net/projects/gendb/. More information on installing GenDB and REGANOR and the system requirements can be found on the GenDB project page http://www.cebitec.uni-bielefeld.de/groups/brf/software/wiki/GenDBWiki/AdministratorDocumentation/GenDBInstallation     

BBProF: An Asynchronous Application Server for Rapid Identification of Proteins Associated with Bacterial Bioleaching

Recovery of metal value, especially from low-grade ores and overburden minerals using acidophilic bacteria through the process of bioleaching is an environmentally benign and commercially scalable biotechnology. In recent years, while the “OMICS” landscape has been witnessing extensive application of computational tools to understand and interpret global biological sequence data, a dedicated bioinformatic server for analysis of bacterial information in the context of its bioleaching ability is not available. We have developed an on-line Bacterial Bioleaching Protein Finder (BBProF) System, which rapidly identifies novel proteins involved in a bacterial bioleaching process and also performs phylogenetic analysis of 16S rRNA genes. BBProF uses the features of Asynchronous Java Script and XML (AJAX) to provide an efficient and fast user experience with minimal requirement of network bandwidth. In the input module the server accepts any bacterial or archaeal complete genome sequence in RAW format and provides a list of proteins involved in the microbial leaching process. BBProF web server is integrated with the European Bioinformatics Institute (EBI) web services such as BLAST for homology search and InterProScan for functional characterization of output protein sequences. Studying evolutionary relationship of bacterial strains of interest using Muscle and ClustalW2 phylogeny web services from EBI is another key feature of our server, where 16S rRNA gene sequences are considered as input through a JQUERY interface along with the sequences present in the BBProF database library. Complete genome sequences of 24 bioleaching microorganism characterized by genomic and physiological study in the laboratory and their respective 16S rRNA gene sequences were stored in the database of the BBProF library. To our knowledge BBProF is the first integrated bioinformatic web server that demonstrates its utility in identifying potential bioleaching bacteria. We hope that the server facilitate ongoing comparative genomic studies on of bioleaching microorganisms and also assist in identification and design of novel microbial consortia that are optimally efficient bioleaching agents.     

siRNA specificity searching incorporating mismatch tolerance data

Artificially synthesized short interfering RNAs (siRNAs) are widely used in functional genomics to knock down specific target genes. One ongoing challenge is to guarantee that the siRNA does not elicit off-target effects. Initial reports suggested that siRNAs were highly sequence-specific; however, subsequent data indicates that this is not necessarily the case. It is still uncertain what level of similarity and other rules are required for an off-target effect to be observed, and scoring schemes have not been developed to look beyond simple measures such as the number of mismatches or the number of consecutive matching bases present. We created design rules for predicting the likelihood of a non-specific effect and present a web server that allows the user to check the specificity of a given siRNA in a flexible manner using a combination of methods. The server finds potential off-target matches in the corresponding RefSeq database and ranks them according to a scoring system based on experimental studies of specificity. AVAILABILITY: The server is available at http://informatics-eskitis.griffith.edu.au/SpecificityServer.     

国内外生物信息学数据库服务新进展

生物信息学是生命科学中最活跃的领域之一. 各类生物信息学数据库在近年不断出现,其规模呈爆炸趋势增长,同时数据结构日趋复杂. 目前生物信息学数据库服务已实现了高度的计算机和网络化. 算法和软件的进步、数据库的一体化、服务器-客户模式的建立使之成为生物、医药、农业等学科的强有力工具. 在国内北京大学物理化学研究所于1996年建立了第一家生物信息学网络服务器. 现已为国内外科学家提供了7万余次服务,在国际上具有一定影响.     

CASVM: web server for SVM-based prediction of caspase substrates cleavage sites

Caspases belong to a unique class of cysteine proteases which function as critical effectors of apoptosis, inflammation and other important cellular processes. Caspases cleave substrates at specific tetrapeptide sites after a highly conserved aspartic acid residue. Prediction of such cleavage sites will complement structural and functional studies on substrates cleavage as well as discovery of new substrates. We have recently developed a support vector machines (SVM) method to address this issue. Our algorithm achieved an accuracy ranging from 81.25 to 97.92%, making it one of the best methods currently available. CASVM is the web server implementation of our SVM algorithms, written in Perl and hosted on a Linux platform. The server can be used for predicting non-canonical caspase substrate cleavage sites. We have also included a relational database containing experimentally verified caspase substrates retrievable using accession IDs, keywords or sequence similarity. AVAILABILITY: http://www.casbase.org/casvm/index.html     

A protein short motif search tool using amino acid sequence and their secondary structure assignment

We present the development of a web server, a protein short motif search tool that allows users to simultaneously search for a protein sequence motif and its secondary structure assignments. The web server is able to query very short motifs searches against PDB structural data from the RCSB Protein Databank, with the users defining the type of secondary structures of the amino acids in the sequence motif. The output utilises 3D visualisation ability that highlights the position of the motif in the structure and on the corresponding sequence. Researchers can easily observe the locations and conformation of multiple motifs among the results. Protein short motif search also has an application programming interface (API) for interfacing with other bioinformatics tools. AVAILABILITY: The database is available for free at http://birg3.fbb.utm.my/proteinsms.     

CBS Genome Atlas Database: a dynamic storage for bioinformatic results and sequence data

SUMMARY: Currently, new bacterial genomes are being published on a monthly basis. With the growing amount of genome sequence data, there is a demand for a flexible and easy-to-maintain structure for storing sequence data and results from bioinformatic analysis. More than 150 sequenced bacterial genomes are now available, and comparisons of properties for taxonomically similar organisms are not readily available to many biologists. In addition to the most basic information, such as AT content, chromosome length, tRNA count and rRNA count, a large number of more complex calculations are needed to perform detailed comparative genomics. DNA structural calculations like curvature and stacking energy, DNA compositions like base skews, oligo skews and repeats at the local and global level are just a few of the analysis that are presented on the CBS Genome Atlas Web page. Complex analysis, changing methods and frequent addition of new models are factors that require a dynamic database layout. Using basic tools like the GNU Make system, csh, Perl and MySQL, we have created a flexible database environment for storing and maintaining such results for a collection of complete microbial genomes. Currently, these results counts to more than 220 pieces of information. The backbone of this solution consists of a program package written in Perl, which enables administrators to synchronize and update the database content. The MySQL database has been connected to the CBS web-server via PHP4, to present a dynamic web content for users outside the center. This solution is tightly fitted to existing server infrastructure and the solutions proposed here can perhaps serve as a template for other research groups to solve database issues. AVAILABILITY: A web based user interface which is dynamically linked to the Genome Atlas Database can be accessed via www.cbs.dtu.dk/services/GenomeAtlas/. SUPPLEMENTARY INFORMATION: This paper has a supplemental information page which links to the examples presented: www.cbs.dtu.dk/services/GenomeAtlas/suppl/bioinfdatabase.     

LOC3D: annotate sub-cellular localization for protein structures

LOC3D (http://cubic.bioc.columbia.edu/db/LOC3d/) is both a weekly-updated database and a web server for predictions of sub-cellular localization for eukaryotic proteins of known three-dimensional (3D) structure. Localization is predicted using four different methods: (i) PredictNLS, prediction of nuclear proteins through nuclear localization signals; (ii) LOChom, inferring localization through sequence homology; (iii) LOCkey, inferring localization through automatic text analysis of SWISS-PROT keywords; and (iv) LOC3Dini, ab initio prediction through a system of neural networks and vector support machines. The final prediction is based on the method that predicts localization with the highest confidence. The LOC3D database currently contains predictions for >8700 eukaryotic protein chains taken from the Protein Data Bank (PDB). The web server can be used to predict sub-cellular localization for proteins for which only a predicted structure is available from threading servers. This makes the resource of particular interest to structural genomics initiatives.     

GenBank.

The GenBank sequence database continues to expand its data coverage, quality control, annotation content and retrieval services for the scientific community. Besides handling direct submissions of sequence data from authors, GenBank also incorporates DNA sequences from all available public sources; an integrated retrieval system, known as Entrez, also makes available data from the major protein sequence and structural databases, and from U.S. and European patents. MIDLINE abstracts from published articles describing the sequences are also included as an additional source of biological annotation for sequence entries. GenBank supports distribution of the data via FTP, CD-ROM, and E-mail servers. Network server-client programs provide access to an integrated database for literature retrieval and sequence similarity searching.     

Tools for comparative protein structure modeling and analysis

The following resources for comparative protein structure modeling and analysis are described (http://salilab.org): MODELLER, a program for comparative modeling by satisfaction of spatial restraints; MODWEB, a web server for automated comparative modeling that relies on PSI-BLAST, IMPALA and MODELLER; MODLOOP, a web server for automated loop modeling that relies on MODELLER; MOULDER, a CPU intensive protocol of MODWEB for building comparative models based on distant known structures; MODBASE, a comprehensive database of annotated comparative models for all sequences detectably related to a known structure; MODVIEW, a Netscape plugin for Linux that integrates viewing of multiple sequences and structures; and SNPWEB, a web server for structure-based prediction of the functional impact of a single amino acid substitution.     

SFESA: a web server for pairwise alignment refinement by secondary structure shifts

Background

Protein sequence alignment is essential for a variety of tasks such as homology modeling and active site prediction. Alignment errors remain the main cause of low-quality structure models. A bioinformatics tool to refine alignments is needed to make protein alignments more accurate.

Results

We developed the SFESA web server to refine pairwise protein sequence alignments. Compared to the previous version of SFESA, which required a set of 3D coordinates for a protein, the new server will search a sequence database for the closest homolog with an available 3D structure to be used as a template. For each alignment block defined by secondary structure elements in the template, SFESA evaluates alignment variants generated by local shifts and selects the best-scoring alignment variant. A scoring function that combines the sequence score of profile-profile comparison and the structure score of template-derived contact energy is used for evaluation of alignments. PROMALS pairwise alignments refined by SFESA are more accurate than those produced by current advanced alignment methods such as HHpred and CNFpred. In addition, SFESA also improves alignments generated by other software.

Conclusions

SFESA is a web-based tool for alignment refinement, designed for researchers to compute, refine, and evaluate pairwise alignments with a combined sequence and structure scoring of alignment blocks. To our knowledge, the SFESA web server is the only tool that refines alignments by evaluating local shifts of secondary structure elements. The SFESA web server is available at http://prodata.swmed.edu/sfesa.     

StressDB: a locally installable web-based relational microarray database designed for small user communities

We have built a microarray database, StressDB, for management of microarray data from our studies on stress-modulated genes in Arabidopsis. StressDB provides small user groups with a locally installable web-based relational microarray database. It has a simple and intuitive architecture and has been designed for cDNA microarray technology users. StressDB uses Windows(trade mark) 2000 as the centralized database server with Oracle(trade mark) 8i as the relational database management system. It allows users to manage microarray data and data-related biological information over the Internet using a web browser. The source-code is currently available on request from the authors and will soon be made freely available for downloading from our website athttp://arastressdb.cac.psu.edu.