UniProt in RDF: Tackling Data Integration and Distributed Annotation with the Semantic Web

The UniProt knowledgebase (UniProtKB) is a comprehensive repository of protein sequence and annotation data. We collect information from the scientific literature and other databases and provide links to over one hundred biological resources. Such links between different databases are an important basis for data integration, but the lack of a common standard to represent and link information makes data integration an expensive business. At UniProt we have started to tackle this problem by using the Resource Description Framework ("http://www.w3.org/RDF/":http://www.w3.org/RDF/) to represent our data. RDF is a core technology for the World Wide Web Consortium's Semantic Web activities ("http://www.w3.org/2001/sw/":http://www.w3.org/2001/sw/) and is therefore well suited to work in a distributed and decentralized environment. The RDF data model represents arbitrary information as a set of simple statements of the form subject-predicate-object. To enable the linking of data on the Web, RDF requires that each resource must have a (globally) unique identifier. These identifiers allow everybody to make statements about a given resource and, together with the simple structure of the RDF data model, make it easy to combine the statements made by different people (or databases) to allow queries across different datasets. RDF is thus an industry standard that can make a major contribution to solve two important problems of bioinformatics: distributed annotation and data integration

FastAlert-an automatic search system to alert about new entries in biological sequence databanks

This paper describes a new tool enabling awareness of new sequence databank entries of interest. The Fast Alert system relieves the researcher from the burden of repeating FASTA searches in order to keep up with the rapidly growing amount of information found in biological sequence databanks. The query sequence can be submitted from any computer connected to the Internet. Upon registration, the databank, including the updates, is scanned at periodic intervals with the sequence provided. The results, so-called FastAlert reports, are delivered via electronic mail. The reports contain the FASTA best-scores list and the similarity statistics for each entry liste

Design and Implementation of the UniProt Website

The UniProt consortium is the main provider of protein sequence and annotation data for much of the life sciences community. The "www.uniprot.org":http://www.uniprot.org website is the primary access point to this data and to documentation and basic tools for the data. This paper discusses the design and implementation of the new website, which was released in July 2008, and shows how it improves data access for users with different levels of experience, as well as to machines for programmatic access

SPARQL-enabled identifier conversion with Identifiers.org

Motivation: On the semantic web, in life sciences in particular, data is often distributed via multiple resources. Each of these sources is likely to use their own International Resource Identifier for conceptually the same resource or database record. The lack of correspondence between identifiers introduces a barrier when executing federated SPARQL queries across life science data. Results: We introduce a novel SPARQL-based service to enable on-the-fly integration of life science data. This service uses the identifier patterns defined in the Identifiers.org Registry to generate a plurality of identifier variants, which can then be used to match source identifiers with target identifiers. We demonstrate the utility of this identifier integration approach by answering queries across major producers of life science Linked Data. Availability and implementation: The SPARQL-based identifier conversion service is available without restriction at http://identifiers.org/services/sparql. Contact: [email protected]

Infrastructure for the life sciences: design and implementation of the UniProt website

<p>Abstract</p> <p>Background</p> <p>The UniProt consortium was formed in 2002 by groups from the Swiss Institute of Bioinformatics (SIB), the European Bioinformatics Institute (EBI) and the Protein Information Resource (PIR) at Georgetown University, and soon afterwards the website <url>http://www.uniprot.org</url> was set up as a central entry point to UniProt resources. Requests to this address were redirected to one of the three organisations' websites. While these sites shared a set of static pages with general information about UniProt, their pages for searching and viewing data were different. To provide users with a consistent view and to cut the cost of maintaining three separate sites, the consortium decided to develop a common website for UniProt. Following several years of intense development and a year of public beta testing, the <url>http://www.uniprot.org</url> domain was switched to the newly developed site described in this paper in July 2008.</p> <p>Description</p> <p>The UniProt consortium is the main provider of protein sequence and annotation data for much of the life sciences community. The <url>http://www.uniprot.org</url> website is the primary access point to this data and to documentation and basic tools for the data. These tools include full text and field-based text search, similarity search, multiple sequence alignment, batch retrieval and database identifier mapping. This paper discusses the design and implementation of the new website, which was released in July 2008, and shows how it improves data access for users with different levels of experience, as well as to machines for programmatic access.</p> <p><url>http://www.uniprot.org/</url> is open for both academic and commercial use. The site was built with open source tools and libraries. Feedback is very welcome and should be sent to <email>[email protected]</email>.</p> <p>Conclusion</p> <p>The new UniProt website makes accessing and understanding UniProt easier than ever. The two main lessons learned are that getting the basics right for such a data provider website has huge benefits, but is not trivial and easy to underestimate, and that there is no substitute for using empirical data throughout the development process to decide on what is and what is not working for your users.</p

Genetic Variations and Diseases in UniProtKB/Swiss-Prot: The Ins and Outs of Expert Manual Curation.

During the last few years, next-generation sequencing (NGS) technologies have accelerated the detection of genetic variants resulting in the rapid discovery of new disease-associated genes. However, the wealth of variation data made available by NGS alone is not sufficient to understand the mechanisms underlying disease pathogenesis and manifestation. Multidisciplinary approaches combining sequence and clinical data with prior biological knowledge are needed to unravel the role of genetic variants in human health and disease. In this context, it is crucial that these data are linked, organized, and made readily available through reliable online resources. The Swiss-Prot section of the Universal Protein Knowledgebase (UniProtKB/Swiss-Prot) provides the scientific community with a collection of information on protein functions, interactions, biological pathways, as well as human genetic diseases and variants, all manually reviewed by experts. In this article, we present an overview of the information content of UniProtKB/Swiss-Prot to show how this knowledgebase can support researchers in the elucidation of the mechanisms leading from a molecular defect to a disease phenotype

HAMAP in 2015: updates to the protein family classification and annotation system.

HAMAP (High-quality Automated and Manual Annotation of Proteins-available at http://hamap.expasy.org/) is a system for the automatic classification and annotation of protein sequences. HAMAP provides annotation of the same quality and detail as UniProtKB/Swiss-Prot, using manually curated profiles for protein sequence family classification and expert curated rules for functional annotation of family members. HAMAP data and tools are made available through our website and as part of the UniRule pipeline of UniProt, providing annotation for millions of unreviewed sequences of UniProtKB/TrEMBL. Here we report on the growth of HAMAP and updates to the HAMAP system since our last report in the NAR Database Issue of 2013. We continue to augment HAMAP with new family profiles and annotation rules as new protein families are characterized and annotated in UniProtKB/Swiss-Prot; the latest version of HAMAP (as of 3 September 2014) contains 1983 family classification profiles and 1998 annotation rules (up from 1780 and 1720). We demonstrate how the complex logic of HAMAP rules allows for precise annotation of individual functional variants within large homologous protein families. We also describe improvements to our web-based tool HAMAP-Scan which simplify the classification and annotation of sequences, and the incorporation of an improved sequence-profile search algorithm

HAMAP in 2015: updates to the protein family classification and annotation system

HAMAP (High-quality Automated and Manual Annotation of Proteins—available at http://hamap.expasy.org/) is a system for the automatic classification and annotation of protein sequences. HAMAP provides annotation of the same quality and detail as UniProtKB/Swiss-Prot, using manually curated profiles for protein sequence family classification and expert curated rules for functional annotation of family members. HAMAP data and tools are made available through our website and as part of the UniRule pipeline of UniProt, providing annotation for millions of unreviewed sequences of UniProtKB/TrEMBL. Here we report on the growth of HAMAP and updates to the HAMAP system since our last report in the NAR Database Issue of 2013. We continue to augment HAMAP with new family profiles and annotation rules as new protein families are characterized and annotated in UniProtKB/Swiss-Prot; the latest version of HAMAP (as of 3 September 2014) contains 1983 family classification profiles and 1998 annotation rules (up from 1780 and 1720). We demonstrate how the complex logic of HAMAP rules allows for precise annotation of individual functional variants within large homologous protein families. We also describe improvements to our web-based tool HAMAP-Scan which simplify the classification and annotation of sequences, and the incorporation of an improved sequence-profile search algorith

An enhanced workflow for variant interpretation in UniProtKB/Swiss-Prot improves consistency and reuse in ClinVar.

Personalized genomic medicine depends on integrated analyses that combine genetic and phenotypic data from individual patients with reference knowledge of the functional and clinical significance of sequence variants. Sources of this reference knowledge include the ClinVar repository of human genetic variants, a community resource that accepts submissions from external groups, and UniProtKB/Swiss-Prot, an expert-curated resource of protein sequences and functional annotation. UniProtKB/Swiss-Prot provides knowledge on the functional impact and clinical significance of over 30 000 human protein-coding sequence variants, curated from peer-reviewed literature reports. Here we present a pilot study that lays the groundwork for the integration of curated knowledge of protein sequence variation from UniProtKB/Swiss-Prot with ClinVar. We show that existing interpretations of variant pathogenicity in UniProtKB/Swiss-Prot and ClinVar are highly concordant, with 88% of variants that are common to the two resources having interpretations of clinical significance that agree. Re-curation of a subset of UniProtKB/Swiss-Prot variants according to American College of Medical Genetics and Genomics (ACMG) guidelines using ClinGen tools further increases this level of agreement, mainly due to the reclassification of supposedly pathogenic variants as benign, based on newly available population frequency data. We have now incorporated ACMG guidelines and ClinGen tools into the UniProt Knowledgebase (UniProtKB) curation workflow and routinely submit variant data from UniProtKB/Swiss-Prot to ClinVar. These efforts will increase the usability and utilization of UniProtKB variant data and will facilitate the continuing (re-)evaluation of clinical variant interpretations as data sets and knowledge evolve