Predictome: a database of putative functional links between proteins

The current deluge of genomic sequences has spawned the creation of tools capable of making sense of the data. Computational and high-throughput experimental methods for generating links between proteins have recently been emerging. These methods effectively act as hypothesis machines, allowing researchers to screen large sets of data to detect interesting patterns that can then be studied in greater detail. Although the potential use of these putative links in predicting gene function has been demonstrated, a central repository for all such links for many genomes would maximize their usefulness. Here we present Predictome, a database of predicted links between the proteins of 44 genomes based on the implementation of three computational methods—chromosomal proximity, phylogenetic profiling and domain fusion—and large-scale experimental screenings of protein–protein interaction data. The combination of data from various predictive methods in one database allows for their comparison with each other, as well as visualization of their correlation with known pathway information. As a repository for such data, Predictome is an ongoing resource for the community, providing functional relationships among proteins as new genomic data emerges. Predictome is available at http://predictome.bu.edu.     

STRING: a database of predicted functional associations between proteins

Functional links between proteins can often be inferred from genomic associations between the genes that encode them: groups of genes that are required for the same function tend to show similar species coverage, are often located in close proximity on the genome (in prokaryotes), and tend to be involved in gene-fusion events. The database STRING is a precomputed global resource for the exploration and analysis of these associations. Since the three types of evidence differ conceptually, and the number of predicted interactions is very large, it is essential to be able to assess and compare the significance of individual predictions. Thus, STRING contains a unique scoring-framework based on benchmarks of the different types of associations against a common reference set, integrated in a single confidence score per prediction. The graphical representation of the network of inferred, weighted protein interactions provides a high-level view of functional linkage, facilitating the analysis of modularity in biological processes. STRING is updated continuously, and currently contains 261 033 orthologs in 89 fully sequenced genomes. The database predicts functional interactions at an expected level of accuracy of at least 80% for more than half of the genes; it is online at http://www.bork.embl-heidelberg.de/STRING/.     

JenPep: a database of quantitative functional peptide data for immunology

MOTIVATION: The compilation of quantitative binding data underlies attempts to derive tools for the accurate prediction of epitopes in cellular immunology and is part of our concerted goal to develop practical computational vaccinology. RESULTS: JenPep is a family of relational databases supporting the growing community of immunoinformaticians. It contains quantitative data on peptide binding to Major Histocompatibility Complexes (MHCs) and to Transmembrane Peptide Transporter (TAP), as well as an annotated list of T-cell epitopes. AVAILABILITY: The database is available via the Internet. An HTML interface allowing searching of the database can be found at the following address: http://www.jenner.ac.uk/JenPep.     

Prolinks: a database of protein functional linkages derived from coevolution

The advent of whole-genome sequencing has led to methods that infer protein function and linkages. We have combined four such algorithms (phylogenetic profile, Rosetta Stone, gene neighbor and gene cluster) in a single database--Prolinks--that spans 83 organisms and includes 10 million high-confidence links. The Proteome Navigator tool allows users to browse predicted linkage networks interactively, providing accompanying annotation from public databases. The Prolinks database and the Proteome Navigator tool are available for use online at http://dip.doe-mbi.ucla.edu/pronav.     

FIMM, a database of functional molecular immunology: update 2002

FIMM database (http://sdmc.krdl.org.sg:8080/fimm) contains data relevant to functional molecular immunology, focusing on cellular immunology. It contains fully referenced data on protein antigens, major histocompatibility complex (MHC) molecules, MHC-associated peptides and relevant disease associations. FIMM has a set of search tools for extraction of information and results are presented as lists or as reports.     

FIMM, a database of functional molecular immunology

FIMM database (http://sdmc.krdl.org.sg:8080/fimm ) contains data relevant to functional molecular immunology, focusing on cellular immunology. It contains fully referenced data on protein antigens, major histocompatibility complex (MHC) molecules, MHC-associated peptides and relevant disease associations. FIMM has a set of search tools for extraction of information and results are presented as lists or as reports.     

miRDB: a microRNA target prediction and functional annotation database with a wiki interface

MicroRNAs (miRNAs) are short noncoding RNAs that are involved in the regulation of thousands of gene targets. Recent studies indicate that miRNAs are likely to be master regulators of many important biological processes. Due to their functional importance, miRNAs are under intense study at present, and many studies have been published in recent years on miRNA functional characterization. The rapid accumulation of miRNA knowledge makes it challenging to properly organize and present miRNA function data. Although several miRNA functional databases have been developed recently, this remains a major bioinformatics challenge to miRNA research community. Here, we describe a new online database system, miRDB, on miRNA target prediction and functional annotation. Flexible web search interface was developed for the retrieval of target prediction results, which were generated with a new bioinformatics algorithm we developed recently. Unlike most other miRNA databases, miRNA functional annotations in miRDB are presented with a primary focus on mature miRNAs, which are the functional carriers of miRNA-mediated gene expression regulation. In addition, a wiki editing interface was established to allow anyone with Internet access to make contributions on miRNA functional annotation. This is a new attempt to develop an interactive community-annotated miRNA functional catalog. All data stored in miRDB are freely accessible at http://mirdb.org.     

Repair-FunMap: a functional database of proteins of the DNA repair systems

Repair-FunMap is a functional database of the DNA repair systems. This database contains not only the proteins directly involved in DNA repair, but also the proteins that interact with the DNA repair proteins. A protein interaction network associated with the human DNA repair processes was established according to the functional relationship between proteins in the database. This network represents the current knowledge on the intrinsic signaling pathways related to DNA repair. The Repair-FunMap could become an essential resource center for cancer research, providing clues to understanding the inter-relationship between proteins in the network, and to building scientific models of the DNA repair processes. AVAILABILITY: http://astro.temple.edu/~feng/Servers/BioinformaticServers.htm     

ProRule: a new database containing functional and structural information on PROSITE profiles

MOTIVATION: Increase the discriminatory power of PROSITE profiles to facilitate function determination and provide biologically relevant information about domains detected by profiles for the annotation of proteins. SUMMARY: We have created a new database, ProRule, which contains additional information about PROSITE profiles. ProRule contains notably the position of structurally and/or functionally critical amino acids, as well as the condition they must fulfill to play their biological role. These supplementary data should help function determination and annotation of the UniProt Swiss-Prot knowledgebase. ProRule also contains information about the domain detected by the profile in the Swiss-Prot line format. Hence, ProRule can be used to make Swiss-Prot annotation more homogeneous and consistent. The format of ProRule can be extended to provide information about combination of domains. AVAILABILITY: ProRule can be accessed through ScanProsite at http://www.expasy.org/tools/scanprosite. A file containing the rules will be made available under the PROSITE copyright conditions on our ftp site (ftp://www.expasy.org/databases/prosite/) by the next PROSITE release.     

Biomolecular interaction network database

This software review looks at the utility of the Biomolecular Interaction Network Database (BIND) as a web database. BIND offers methods common to related biology databases and specialisations for its protein interaction data. Searching and browsing this database is easy and well integrated with the underlying data and the needs of scientists. Interaction networks are visualised with software that offers many useful options. The innovative ontoglyphs are used throughout to provide visual cues to protein functions, localisation and other aspects one needs to know for this data set. One can expect to get useful results that may be well integrated with one's research needs.     

Update of KEYnet: a gene and protein names database for biosequences functional organisation

KEYnet is a database where gene and protein names are hierarchically structured. Particular care has been devoted to the search and organisation of synonyms. The structuring is based on biological criteria in order to assist the user in data search and to minimise the risk of information loss. Links to the EMBL data library by the entry name and the accession number are implemented. KEYnet is available through the WWW at the following site: http://www.ba.cnr.it/keynet.html     

SNPdbe: constructing an nsSNP functional impacts database

Many existing databases annotate experimentally characterized single nucleotide polymorphisms (SNPs). Each non-synonymous SNP (nsSNP) changes one amino acid in the gene product (single amino acid substitution;SAAS). This change can either affect protein function or be neutral in that respect. Most polymorphisms lack experimental annotation of their functional impact. Here, we introduce SNPdbe-SNP database of effects, with predictions of computationally annotated functional impacts of SNPs. Database entries represent nsSNPs in dbSNP and 1000 Genomes collection, as well as variants from UniProt and PMD. SAASs come from >2600 organisms; 'human' being the most prevalent. The impact of each SAAS on protein function is predicted using the SNAP and SIFT algorithms and augmented with experimentally derived function/structure information and disease associations from PMD, OMIM and UniProt. SNPdbe is consistently updated and easily augmented with new sources of information. The database is available as an MySQL dump and via a web front end that allows searches with any combination of organism names, sequences and mutation IDs. AVAILABILITY: http://www.rostlab.org/services/snpdbe.     

iGNM: a database of protein functional motions based on Gaussian Network Model

MOTIVATION: The knowledge of protein structure is not sufficient for understanding and controlling its function. Function is a dynamic property. Although protein structural information has been rapidly accumulating in databases, little effort has been invested to date toward systematically characterizing protein dynamics. The recent success of analytical methods based on elastic network models, and in particular the Gaussian Network Model (GNM), permits us to perform a high-throughput analysis of the collective dynamics of proteins. RESULTS: We computed the GNM dynamics for 20 058 structures from the Protein Data Bank, and generated information on the equilibrium dynamics at the level of individual residues. The results are stored on a web-based system called iGNM and configured so as to permit the users to visualize or download the results through a standard web browser using a simple search engine. Static and animated images for describing the conformational mobility of proteins over a broad range of normal modes are accessible, along with an online calculation engine available for newly deposited structures. A case study of the dynamics of 20 non-homologous hydrolases is presented to illustrate the utility of the iGNM database for identifying key residues that control the cooperative motions and revealing the connection between collective dynamics and catalytic activity.     

Expression and functional characterization of SCaMPER: a sphingolipid-modulated calcium channel of cardiomyocytes

Calciumchannels are important in a variety of cellular events including musclecontraction, signaling, proliferation, and apoptosis.Sphingolipids have been recognized as mediators of intracellularcalcium release through their actions on a calcium channel,sphingolipid calcium release-mediating protein of the endoplasmicreticulum (SCaMPER). The current study investigates the expression andfunction of SCaMPER in cardiomyocytes. Northern analyses and RT-PCRcloning and sequencing revealed SCaMPER expression in both human andrat cardiac tissue. Immunofluorescence and Western blot analysesdemonstrated that SCaMPER is abundant in cardiac tissue and islocalized to the sarcotubular junction. This was confirmed by thecolocalization of SCaMPER with dihydropyridine and ryanodine receptorsby confocal microscopy. Purified T tubules were shown to containSCaMPER and immunoelectron micrographs suggested that SCaMPER islocated to the junctional T tubules, but a junctional SR localizationcannot be ruled out. The sphingolipid ligand for SCaMPER,sphingosylphosphorylcholine (SPC), initiated calcium release from thecardiomyocyte SR. Importantly, antisense knockdown of SCaMPER mRNAproduced a substantial reduction of sphingolipid-induced calciumrelease, suggesting that SCaMPER is a potentially important calciumchannel of cardiomyocytes.

     

Sebida: a database for the functional and evolutionary analysis of genes with sex-biased expression

We describe Sebida, a database of genes with sex-biased expression. The database integrates results from multiple, independent microarray studies comparing male and female gene expression in Drosophila melanogaster, Drosophila simulans and Anopheles gambiae. Sebida uses standard nomenclature, which allows individual genes to be compared across different microarray platforms and to be queried by gene name, symbol, or annotation number. In addition to ratios of male/female expression for each gene, Sebida also contains information useful for evolutionary studies, such as local recombination rate, degree of codon bias and interspecific divergence at synonymous and non-synonymous sites. AVAILABILITY: Sebida can be accessed at http://www.sebida.de