A database of germline p53 mutations in cancer-prone families.

We created a comprehensive database covering all published cases of germline p53 mutations. The current version lists 580 tumours in 448 individuals belonging to 122 independent pedigrees. The database describes each p53 mutation (type of the mutation, exon and codon affected by the mutation, nucleotide and amino acid change), each family (family history of cancer, diagnosis of Li-Fraumeni syndrome), each affected individual (sex, generation, p53 status, from which parent the mutation was inherited) and each tumour (type, age of onset, p53 status-loss of heterozygosity, immunostaining). Each entry contains the original reference(s). The database is freely available and can be obtained from http://www.lf2.cuni.cz     

EMBL-Align: a new public nucleotide and amino acid multiple sequence alignment database

The submission of multiple sequence alignment data to EMBL has grown 30-fold in the past 10 years, creating a problem of archiving them. The EBI has developed a new public database of multiple sequence alignments called EMBL-Align. It has a dedicated web-based submission tool, Webin-Align. Together they represent a comprehensive data management solution for alignment data. Webin-Align accepts all the common alignment formats and can display data in CLUSTALW format as well as a new standard EMBL-Align flat file format. The alignments are stored in the EMBL-Align database and can be queried from the EBI SRS (Sequence Retrieval System) server. AVAILABILITY: Webin-Align: http://www.ebi.ac.uk/embl/Submission/align_top.html, EMBL-Align: ftp://ftp.ebi.ac.uk/pub/databases/embl/align, http://srs.ebi.ac.uk/     

The radiation hybrid database.

Since July 1995, the European Bioinformatics Institute (EBI) has maintained the Radiation Hybrid database (RHdb; http://www.ebi.ac. uk/RHdb ), a public database for radiation hybrid data. Radiation hybrid mapping is an important technique for determining high resolution maps. Recently, CORBA access has been added to RHdb. The EBI is an Outstation of the European Molecular Biology Laboratory (EMBL).     

The HuGeMap Database: interconnection and visualization of human genome maps.

The HuGeMap database stores the major genetic and physical maps of the human genome. HuGeMap is accessible on the Web at http://www. infobiogen.fr/services/Hugemap and through a CORBA server. A standard genome map data format for the interconnection of genome map databases was defined in collaboration with the EBI. The HuGeMap CORBA server provides this interconnection using the interface definition language IDL. Two graphical user interfaces were developed for the visualization of the HuGeMap data: ZoomMap (http://www.infobiogen.fr/services/zomit/Zoom Map.html) for navigation by zooming and data transformation via magic lenses, and MappetShow (http://www.infobiogen.fr/services/Mappet) for visualizing and comparing maps.     

RHdb: the radiation hybrid database

Since July 1995, the European Bioinformatics Institute (EBI) has maintained RHdb (http://www.ebi.ac.uk/RHdb ), a public database for radiation hybrid data. Radiation hybrid mapping is an important technique for determining high resolution maps. RHdb is also served by CORBA servers. The EBI is an Outstation of the European Molecular Biology Laboratory (EMBL).     

RHdb: the Radiation Hybrid database

Since July 1995, the European Bioinformatics Institute (EBI) has maintained RHdb (http://www.ebi.ac.uk/RHdb), a public database for radiation hybrid data. Radiation hybrid mapping is an important technique for determining high resolution maps. RHdb is also served by CORBA servers. The EBI is an Outstation of the European Molecular Biology Laboratory (EMBL).     

The Radiation Hybrid Database.

Since July 1995, the European Bioinformatics Institute (EBI) has maintained RHdb (http://www.ebi.ac.uk/RHdb/RHdb.html ), a public database for radiation hybrid data. Radiation hybrid mapping is an important technique for determining high resolution maps. Recently, CORBA access has been added to Rhdb. The EBI is an Outstation of the European Molecular Biology Laboratory (EMBL).     

Codon usage tabulated from international DNA sequence databases: status for the year 2000

The frequencies of each of the 257 468 complete protein coding sequences (CDSs) have been compiled from the taxonomical divisions of the GenBank DNA sequence database. The sum of the codons used by 8792 organisms has also been calculated. The data files can be obtained from the anonymous ftp sites of DDBJ, Kazusa and EBI. A list of the codon usage of genes and the sum of the codons used by each organism can be obtained through the web site http://www.kazusa.or.jp/codon/ . The present study also reports recent developments on the WWW site. The new web interface provides data in the CodonFrequency-compatible format as well as in the traditional table format. The use of the database is facilitated by keyword based search analysis and the availability of codon usage tables for selected genes from each species. These new tools will provide users with the ability to further analyze for variations in codon usage among different genomes.     

NPIDB: a database of nucleic acids-protein interactions

The database NPIDB (Nucleic Acids-Protein Interaction DataBase) contains information derived from structures of DNA-protein and RNA-protein complexes extracted from PDB (1834 complexes in July 2007). It is organized as a collection of files in PDB format and is equipped with a web-interface and a set of tools for extracting biologically meaningful characteristics of complexes. The content of the database is weekly updated. AVAILABILITY: http://monkey.belozersky.msu.ru/NPIDB/     

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.     

Identification of two poorly prognosed ovarian carcinoma subtypes associated with CHEK2 germ-line mutation and non-CHEK2 somatic mutation gene signatures

High-grade serous ovarian cancer (HG-SOC), a major histologic type of epithelial ovarian cancer (EOC), is a poorly-characterized, heterogeneous and lethal disease where somatic mutations of TP53 are common and inherited loss-of-function mutations in BRCA1/2 predispose to cancer in 9.5–13% of EOC patients. However, the overall burden of disease due to either inherited or sporadic mutations is not known.

We performed bioinformatics analyses of mutational and clinical data of 334 HG-SOC tumor samples from The Cancer Genome Atlas to identify novel tumor-driving mutations, survival-significant patient subgroups and tumor subtypes potentially driven by either hereditary or sporadic factors.

We identified a sub-cluster of high-frequency mutations in 22 patients and 58 genes associated with DNA damage repair, apoptosis and cell cycle. Mutations of CHEK2, observed with the highest intensity, were associated with poor therapy response and overall survival (OS) of these patients (P = 8.00e-05), possibly due to detrimental effect of mutations at the nuclear localization signal. A 21-gene mutational prognostic signature significantly stratifies patients into relatively low or high-risk subgroups with 5-y OS of 37% or 6%, respectively (P = 7.31e-08). Further analysis of these genes and high-risk subgroup revealed 2 distinct classes of tumors characterized by either germline mutations of genes such as CHEK2, RPS6KA2 and MLL4, or somatic mutations of other genes in the signature.

Our results could provide improvement in prediction and clinical management of HG-SOC, facilitate our understanding of this complex disease, guide the design of targeted therapeutics and improve screening efforts to identify women at high-risk of hereditary ovarian cancers distinct from those associated with BRCA1/2 mutations.     

ArrayExpress--a public repository for microarray gene expression data at the EBI

ArrayExpress is a new public database of microarray gene expression data at the EBI, which is a generic gene expression database designed to hold data from all microarray platforms. ArrayExpress uses the annotation standard Minimum Information About a Microarray Experiment (MIAME) and the associated XML data exchange format Microarray Gene Expression Markup Language (MAGE-ML) and it is designed to store well annotated data in a structured way. The ArrayExpress infrastructure consists of the database itself, data submissions in MAGE-ML format or via an online submission tool MIAMExpress, online database query interface, and the Expression Profiler online analysis tool. ArrayExpress accepts three types of submission, arrays, experiments and protocols, each of these is assigned an accession number. Help on data submission and annotation is provided by the curation team. The database can be queried on parameters such as author, laboratory, organism, experiment or array types. With an increasing number of organisations adopting MAGE-ML standard, the volume of submissions to ArrayExpress is increasing rapidly. The database can be accessed at http://www.ebi.ac.uk/arrayexpress.     

Marfan Database (third edition): new mutations and new routines for the software.

The Marfan database is a software that contains routines for the analysis of mutations identified in the FBN1 gene that encodes fibrillin-1. Mutations in this gene are associated not only with Marfan syndrome but also with a spectrum of overlapping disorders. The third version of the Marfan database contains 137 entries. The software has been modified to accommodate four new routines and is now accessible on the World Wide Web at http://www.umd.necker.fr     

Update of the Human MitBASE database.

Human MitBASE is a database collecting human mtDNA variants. This database is part of a greater mitochondrial genome database (MitBASE) funded within the EU Biotech Program. The present paper reports the recent improvements in data structure, data quality and data quantity. As far as the database structure is concerned it is now fully designed and implemented. Based on the previously described structure some changes have been made to optimise both data input and data quality. Cross-references with other bio-databases (EMBL, OMIM, MEDLINE) have been implemented. Human MitBASE data can be queried with the MitBASE Simple Query System (http://www.ebi.ac.uk/htbin/Mitbase/mit base.pl) and with SRS at the EBI under the 'Mutation' section (http://srs.ebi.ac.uk/srs5/). At present the HumanMitBASE node contains approximately 5000 variants related to studies investigating population polymorphisms and pathologies.     

The Human PAX6 Mutation Database.

The Human PAX6 Mutation Database contains details of 94 mutations of the PAX6 gene. A Microsoft Access program is used by the Curator to store, update and search the database entries. Mutations can be entered directly by the Curator, or imported from submissions made via the World Wide Web. The PAX6 Mutation Database web page at URL http://www.hgu.mrc.ac.uk/Softdata/PAX6/ provides information about PAX6, as well as a fill-in form through which new mutations can be submitted to the Curator. A search facility allows remote users to query the database. A plain text format file of the data can be downloaded via the World Wide Web. The Curation program contains prior knowledge of the genetic code and of the PAX6 gene including cDNA sequence, location of intron/exon boundaries, and protein domains, so that the minimum of information need be provided by the submitter or Curator.     

LDLR Database (second edition): new additions to the database and the software, and results of the first molecular analysis.

Mutations in the LDL receptor gene (LDLR) cause familial hypercholesterolemia (FH), a common autosomal dominant disorder. The LDLR database is a computerized tool that has been developed to provide tools to analyse the numerous mutations that have been identified in the LDLR gene. The second version of the LDLR database contains 140 new entries and the software has been modified to accommodate four new routines. The analysis of the updated data (350 mutations) gives the following informations: (i) 63% of the mutations are missense, and only 20% occur in CpG dinucleotides; (ii) although the mutations are widely distributed throughout the gene, there is an excess of mutations in exons 4 and 9, and a deficit in exons 13 and 15; (iii) the analysis of the distribution of mutations located within the ligand-binding domain shows that 74% of the mutations in this domain affect a conserved amino-acid, and that they are mostly confined in the C-terminal region of the repeats. Conversely, the same analysis in the EGF-like domain shows that 64% of the mutations in this domain affect a non-conserved amino-acid, and, that they are mostly confined in the N-terminal half of the repeats. The database is now accessible on the World Wide Web at http://www.umd.necker.fr     

The EMBL Nucleotide Sequence Database: major new developments

The EMBL Nucleotide Sequence Database (http://www.ebi.ac.uk/embl/) incorporates, organizes and distributes nucleotide sequences from all available public sources. The database is located and maintained at the European Bioinformatics Institute (EBI) near Cambridge, UK. In an international collaboration with DDBJ (Japan) and GenBank (USA), data are exchanged amongst the collaborating databases on a daily basis to achieve optimal synchronization. Webin is the preferred web-based submission system for individual submitters, while automatic procedures allow incorporation of sequence data from large-scale genome sequencing centres and from the European Patent Office (EPO). Database releases are produced quarterly. Network services allow free access to the most up-to-date data collection via FTP, Email and World Wide Web interfaces. EBI's Sequence Retrieval System (SRS) integrates and links the main nucleotide and protein databases plus many other specialized molecular biology databases. For sequence similarity searching, a variety of tools (e.g. Fasta, BLAST) are available which allow external users to compare their own sequences against the latest data in the EMBL Nucleotide Sequence Database and SWISS-PROT. All resources can be accessed via the EBI home page at http://www.ebi.ac.uk.     

TSGDB: a database system for tumor suppressor genes

A Web-based database system was constructed and implemented that contains 174 tumor suppressor genes. The database homepage was created to accommodate these genes in a pull-down window so that each gene can be viewed individually in a separate Web page. Information displayed on each page includes gene name, aliases, source organism, chromosome location, expression cells/tissues, gene structure, protein size, gene functions and major reference sources. Queries to the database can be conducted through a user-friendly interface, and query results are returned in the HTML format on dynamically generated web pages. AVAILABILITY: The database is available at http://www.cise.ufl.edu/~yy1/HTML-TSGDB/Homepage.html (data files also at http://www.patcar.org/Databases/Tumor_Suppressor_Genes)     

The PROSITE database, its status in 1999.

The PROSITE database (http://www.expasy.ch/sprot/prosite.htm l) consists of biologically significant patterns and profiles formulated in such a way that with appropriate computational tools it can help to determine to which known family of protein (if any) a new sequence belongs, or which known domain(s) it contains.