SIMAP—structuring the network of protein similarities

Protein sequences are the most important source of evolutionary and functional information for new proteins. In order to facilitate the computationally intensive tasks of sequence analysis, the Similarity Matrix of Proteins (SIMAP) database aims to provide a comprehensive and up-to-date dataset of the pre-calculated sequence similarity matrix and sequence-based features like InterPro domains for all proteins contained in the major public sequence databases. As of September 2007, SIMAP covers ∼17 million proteins and more than 6 million non-redundant sequences and provides a complete annotation based on InterPro 16. Novel features of SIMAP include a new, portlet-based web portal providing multiple, structured views on retrieved proteins and integration of protein clusters and a unique search method for similar domain architectures. Access to SIMAP is freely provided for academic use through the web portal for individuals at http://mips.gsf.de/simap/and through Web Services for programmatic access at http://mips.gsf.de/webservices/services/SimapService2.0?wsdl

ProteinWorldDB: querying radical pairwise alignments among protein sets from complete genomes

Motivation: Many analyses in modern biological research are based on comparisons between biological sequences, resulting in functional, evolutionary and structural inferences. When large numbers of sequences are compared, heuristics are often used resulting in a certain lack of accuracy. In order to improve and validate results of such comparisons, we have performed radical all-against-all comparisons of 4 million protein sequences belonging to the RefSeq database, using an implementation of the Smith–Waterman algorithm. This extremely intensive computational approach was made possible with the help of World Community Grid™, through the Genome Comparison Project. The resulting database, ProteinWorldDB, which contains coordinates of pairwise protein alignments and their respective scores, is now made available. Users can download, compare and analyze the results, filtered by genomes, protein functions or clusters. ProteinWorldDB is integrated with annotations derived from Swiss-Prot, Pfam, KEGG, NCBI Taxonomy database and gene ontology. The database is a unique and valuable asset, representing a major effort to create a reliable and consistent dataset of cross-comparisons of the whole protein content encoded in hundreds of completely sequenced genomes using a rigorous dynamic programming approach

FGDB: revisiting the genome annotation of the plant pathogen Fusarium graminearum

The MIPS Fusarium graminearum Genome Database (FGDB) was established as a comprehensive genome database on one of the most devastating fungal plant pathogens of wheat, barley and maize. The current version of FGDB v3.1 provides information on the full manually revised gene set based on the Broad Institute assembly FG3 genome sequence. The results of gene prediction tools were integrated with the help of comparative data on related species to result in a set of 13.718 annotated protein coding genes. This rigorous approach involved adding or modifying gene models and represents a coding sequence gold standard for the genus Fusarium. The gene loci improvements results in 2461 genes which either are new or have different structures compared to the Broad Institute assembly 3 gene set. Moreover the database serves as a convenient entry point to explore expression data results and to obtain information on the Affymetrix GeneChip probe sets. The resource is accessible on http://mips.gsf.de/genre/proj/FGDB/

PEDANT covers all complete RefSeq genomes

The PEDANT genome database provides exhaustive annotation of nearly 3000 publicly available eukaryotic, eubacterial, archaeal and viral genomes with more than 4.5 million proteins by a broad set of bioinformatics algorithms. In particular, all completely sequenced genomes from the NCBI's Reference Sequence collection (RefSeq) are covered. The PEDANT processing pipeline has been sped up by an order of magnitude through the utilization of precalculated similarity information stored in the similarity matrix of proteins (SIMAP) database, making it possible to process newly sequenced genomes immediately as they become available. PEDANT is freely accessible to academic users at http://pedant.gsf.de. For programmatic access Web Services are available at http://pedant.gsf.de/webservices.jsp

Gene3D: merging structure and function for a Thousand genomes

Over the last 2 years the Gene3D resource has been significantly improved, and is now more accurate and with a much richer interactive display via the Gene3D website (http://gene3d.biochem.ucl.ac.uk/). Gene3D provides accurate structural domain family assignments for over 1100 genomes and nearly 10 000 000 proteins. A hidden Markov model library, constructed from the manually curated CATH structural domain hierarchy, is used to search UniProt, RefSeq and Ensembl protein sequences. The resulting matches are refined into simple multi-domain architectures using a recently developed in-house algorithm, DomainFinder 3 (available at: ftp://ftp.biochem.ucl.ac.uk/pub/gene3d_data/DomainFinder3/). The domain assignments are integrated with multiple external protein function descriptions (e.g. Gene Ontology and KEGG), structural annotations (e.g. coiled coils, disordered regions and sequence polymorphisms) and family resources (e.g. Pfam and eggNog) and displayed on the Gene3D website. The website allows users to view descriptions for both single proteins and genes and large protein sets, such as superfamilies or genomes. Subsets can then be selected for detailed investigation or associated functions and interactions can be used to expand explorations to new proteins. Gene3D also provides a set of services, including an interactive genome coverage graph visualizer, DAS annotation resources, sequence search facilities and SOAP services

DAhunter: a web-based server that identifies homologous proteins by comparing domain architecture

We present DAhunter, a web-based server that identifies homologous proteins by comparing domain architectures, the organization of protein domains. A major obstacle in comparison of domain architecture is the existence of ‘promiscuous’ domains, which carry out auxiliary functions and appear in many unrelated proteins. To distinguish these promiscuous domains from protein domains, we assigned a weight score to each domain extracted from RefSeq proteins, based on its abundance and versatility. A domain's score represents its importance in the ‘protein world’ and is used in the comparison of domain architectures. In scoring domains, DAhunter also considers domain combinations as well as single domains. To measure the similarity of two domain architectures, we developed several methods that are based on algorithms used in information retrieval (the cosine similarity, the Goodman–Kruskal γ function, and domain duplication index) and then combined these into a similarity score. Compared with other domain architecture algorithms, DAhunter is better at identifying homology. The server is available at http://www.dahunter.kr and http://localodom.kobic.re.kr/dahunter/index.ht

The Gene3D Web Services: a platform for identifying, annotating and comparing structural domains in protein sequences

The Gene3D structural domain database provides domain annotations for 7 million proteins, based on the manually curated structural domain superfamilies in CATH. These annotations are integrated with functional, genomic and molecular information from external resources, such as GO, EC, UniProt and the NCBI Taxonomy database. We have constructed a set of web services that provide programmatic access to this integrated database, as well as the Gene3D domain recognition tool (Gene3DScan) and protein sequence annotation pipeline for analysing novel protein sequences. Example queries include retrieving all curated GO terms for a domain superfamily or all the multi-domain architectures for the human genome. The services can be accessed using simple HTTP calls and are able to return results in a range of formats for quick downloading and easy parsing, graphical rendering and data storage. Hence, they provide a simple, but flexible means of integrating domain annotations and associated data sets into locally run pipelines and analysis software. The services can be found at http://gene3d.biochem.ucl.ac.uk/WebServices/

B2G-FAR, a species-centered GO annotation repository

Motivation: Functional genomics research has expanded enormously in the last decade thanks to the cost reduction in high-throughput technologies and the development of computational tools that generate, standardize and share information on gene and protein function such as the Gene Ontology (GO). Nevertheless, many biologists, especially working with non-model organisms, still suffer from non-existing or low-coverage functional annotation, or simply struggle retrieving, summarizing and querying these data

SIMAP--the database of all-against-all protein sequence similarities and annotations with new interfaces and increased coverage

The Similarity Matrix of Proteins (SIMAP, http://mips.gsf.de/simap/) database has been designed to massively accelerate computationally expensive protein sequence analysis tasks in bioinformatics. It provides pre-calculated sequence similarities interconnecting the entire known protein sequence universe, complemented by pre-calculated protein features and domains, similarity clusters and functional annotations. SIMAP covers all major public protein databases as well as many consistently re-annotated metagenomes from different repositories. As of September 2013, SIMAP contains >163 million proteins corresponding to ∼70 million non-redundant sequences. SIMAP uses the sensitive FASTA search heuristics, the Smith–Waterman alignment algorithm, the InterPro database of protein domain models and the BLAST2GO functional annotation algorithm. SIMAP assists biologists by facilitating the interactive exploration of the protein sequence universe. Web-Service and DAS interfaces allow connecting SIMAP with any other bioinformatic tool and resource. All-against-all protein sequence similarity matrices of project-specific protein collections are generated on request. Recent improvements allow SIMAP to cover the rapidly growing sequenced protein sequence universe. New Web-Service interfaces enhance the connectivity of SIMAP. Novel tools for interactive extraction of protein similarity networks have been added. Open access to SIMAP is provided through the web portal; the portal also contains instructions and links for software access and flat file downloads