STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. [PMID: 30476243]
Damian Szklarczyk, Annika L Gable, David Lyon, Alexander Junge, Stefan Wyder, Jaime Huerta-Cepas, Milan Simonovic, Nadezhda T Doncheva, John H Morris, Peer Bork, Lars J Jensen, Christian von Mering
Proteins and their functional interactions form the backbone of the cellular machinery. Their connectivity network needs to be considered for the full understanding of biological phenomena, but the available information on protein-protein associations is incomplete and exhibits varying levels of annotation granularity and reliability. The STRING database aims to collect, score and integrate all publicly available sources of protein-protein interaction information, and to complement these with computational predictions. Its goal is to achieve a comprehensive and objective global network, including direct (physical) as well as indirect (functional) interactions. The latest version of STRING (11.0) more than doubles the number of organisms it covers, to 5090. The most important new feature is an option to upload entire, genome-wide datasets as input, allowing users to visualize subsets as interaction networks and to perform gene-set enrichment analysis on the entire input. For the enrichment analysis, STRING implements well-known classification systems such as Gene Ontology and KEGG, but also offers additional, new classification systems based on high-throughput text-mining as well as on a hierarchical clustering of the association network itself. The STRING resource is available online at https://string-db.org/.
Nucleic Acids Res 2019:47(D1)
3 Citations (from Europe PMC, 2019-07-27)
The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. [PMID: 27924014]
Damian Szklarczyk, John H Morris, Helen Cook, Michael Kuhn, Stefan Wyder, Milan Simonovic, Alberto Santos, Nadezhda T Doncheva, Alexander Roth, Peer Bork, Lars J Jensen, Christian von Mering
A system-wide understanding of cellular function requires knowledge of all functional interactions between the expressed proteins. The STRING database aims to collect and integrate this information, by consolidating known and predicted protein-protein association data for a large number of organisms. The associations in STRING include direct (physical) interactions, as well as indirect (functional) interactions, as long as both are specific and biologically meaningful. Apart from collecting and reassessing available experimental data on protein-protein interactions, and importing known pathways and protein complexes from curated databases, interaction predictions are derived from the following sources: (i) systematic co-expression analysis, (ii) detection of shared selective signals across genomes, (iii) automated text-mining of the scientific literature and (iv) computational transfer of interaction knowledge between organisms based on gene orthology. In the latest version 10.5 of STRING, the biggest changes are concerned with data dissemination: the web frontend has been completely redesigned to reduce dependency on outdated browser technologies, and the database can now also be queried from inside the popular Cytoscape software framework. Further improvements include automated background analysis of user inputs for functional enrichments, and streamlined download options. The STRING resource is available online, at http://string-db.org/. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.
Nucleic Acids Res 2017:45(D1)
865 Citations (from Europe PMC, 2019-09-03)
STRING v10: protein-protein interaction networks, integrated over the tree of life. [PMID: 25352553]
Damian Szklarczyk, Andrea Franceschini, Stefan Wyder, Kristoffer Forslund, Davide Heller, Jaime Huerta-Cepas, Milan Simonovic, Alexander Roth, Alberto Santos, Kalliopi P Tsafou, Michael Kuhn, Peer Bork, Lars J Jensen, Christian von Mering
The many functional partnerships and interactions that occur between proteins are at the core of cellular processing and their systematic characterization helps to provide context in molecular systems biology. However, known and predicted interactions are scattered over multiple resources, and the available data exhibit notable differences in terms of quality and completeness. The STRING database (http://string-db.org) aims to provide a critical assessment and integration of protein-protein interactions, including direct (physical) as well as indirect (functional) associations. The new version 10.0 of STRING covers more than 2000 organisms, which has necessitated novel, scalable algorithms for transferring interaction information between organisms. For this purpose, we have introduced hierarchical and self-consistent orthology annotations for all interacting proteins, grouping the proteins into families at various levels of phylogenetic resolution. Further improvements in version 10.0 include a completely redesigned prediction pipeline for inferring protein-protein associations from co-expression data, an API interface for the R computing environment and improved statistical analysis for enrichment tests in user-provided networks. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.
Nucleic Acids Res 2015:43(Database issue)
2399 Citations (from Europe PMC, 2019-09-27)
STRING v9.1: protein-protein interaction networks, with increased coverage and integration. [PMID: 23203871]
Andrea Franceschini, Damian Szklarczyk, Sune Frankild, Michael Kuhn, Milan Simonovic, Alexander Roth, Jianyi Lin, Pablo Minguez, Peer Bork, Christian von Mering, Lars J Jensen
Complete knowledge of all direct and indirect interactions between proteins in a given cell would represent an important milestone towards a comprehensive description of cellular mechanisms and functions. Although this goal is still elusive, considerable progress has been made-particularly for certain model organisms and functional systems. Currently, protein interactions and associations are annotated at various levels of detail in online resources, ranging from raw data repositories to highly formalized pathway databases. For many applications, a global view of all the available interaction data is desirable, including lower-quality data and/or computational predictions. The STRING database (http://string-db.org/) aims to provide such a global perspective for as many organisms as feasible. Known and predicted associations are scored and integrated, resulting in comprehensive protein networks covering >1100 organisms. Here, we describe the update to version 9.1 of STRING, introducing several improvements: (i) we extend the automated mining of scientific texts for interaction information, to now also include full-text articles; (ii) we entirely re-designed the algorithm for transferring interactions from one model organism to the other; and (iii) we provide users with statistical information on any functional enrichment observed in their networks.
Nucleic Acids Res 2013:41(Database issue)
1800 Citations (from Europe PMC, 2019-09-27)
The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. [PMID: 21045058]
Damian Szklarczyk, Andrea Franceschini, Michael Kuhn, Milan Simonovic, Alexander Roth, Pablo Minguez, Tobias Doerks, Manuel Stark, Jean Muller, Peer Bork, Lars J Jensen, Christian von Mering
An essential prerequisite for any systems-level understanding of cellular functions is to correctly uncover and annotate all functional interactions among proteins in the cell. Toward this goal, remarkable progress has been made in recent years, both in terms of experimental measurements and computational prediction techniques. However, public efforts to collect and present protein interaction information have struggled to keep up with the pace of interaction discovery, partly because protein-protein interaction information can be error-prone and require considerable effort to annotate. Here, we present an update on the online database resource Search Tool for the Retrieval of Interacting Genes (STRING); it provides uniquely comprehensive coverage and ease of access to both experimental as well as predicted interaction information. Interactions in STRING are provided with a confidence score, and accessory information such as protein domains and 3D structures is made available, all within a stable and consistent identifier space. New features in STRING include an interactive network viewer that can cluster networks on demand, updated on-screen previews of structural information including homology models, extensive data updates and strongly improved connectivity and integration with third-party resources. Version 9.0 of STRING covers more than 1100 completely sequenced organisms; the resource can be reached at http://string-db.org.
Nucleic Acids Res 2011:39(Database issue)
1575 Citations (from Europe PMC, 2019-09-27)
STRING 8--a global view on proteins and their functional interactions in 630 organisms. [PMID: 18940858]
Lars J Jensen, Michael Kuhn, Manuel Stark, Samuel Chaffron, Chris Creevey, Jean Muller, Tobias Doerks, Philippe Julien, Alexander Roth, Milan Simonovic, Peer Bork, Christian von Mering
Functional partnerships between proteins are at the core of complex cellular phenotypes, and the networks formed by interacting proteins provide researchers with crucial scaffolds for modeling, data reduction and annotation. STRING is a database and web resource dedicated to protein-protein interactions, including both physical and functional interactions. It weights and integrates information from numerous sources, including experimental repositories, computational prediction methods and public text collections, thus acting as a meta-database that maps all interaction evidence onto a common set of genomes and proteins. The most important new developments in STRING 8 over previous releases include a URL-based programming interface, which can be used to query STRING from other resources, improved interaction prediction via genomic neighborhood in prokaryotes, and the inclusion of protein structures. Version 8.0 of STRING covers about 2.5 million proteins from 630 organisms, providing the most comprehensive view on protein-protein interactions currently available. STRING can be reached at http://string-db.org/.
Nucleic Acids Res 2009:37(Database issue)
1174 Citations (from Europe PMC, 2019-09-27)
STRING 7--recent developments in the integration and prediction of protein interactions. [PMID: 17098935]
Christian von Mering, Lars J Jensen, Michael Kuhn, Samuel Chaffron, Tobias Doerks, Beate Krüger, Berend Snel, Peer Bork
Information on protein-protein interactions is still mostly limited to a small number of model organisms, and originates from a wide variety of experimental and computational techniques. The database and online resource STRING generalizes access to protein interaction data, by integrating known and predicted interactions from a variety of sources. The underlying infrastructure includes a consistent body of completely sequenced genomes and exhaustive orthology classifications, based on which interaction evidence is transferred between organisms. Although primarily developed for protein interaction analysis, the resource has also been successfully applied to comparative genomics, phylogenetics and network studies, which are all facilitated by programmatic access to the database backend and the availability of compact download files. As of release 7, STRING has almost doubled to 373 distinct organisms, and contains more than 1.5 million proteins for which associations have been pre-computed. Novel features include AJAX-based web-navigation, inclusion of additional resources such as BioGRID, and detailed protein domain annotation. STRING is available at http://string.embl.de/
Nucleic Acids Res 2007:35(Database issue)
340 Citations (from Europe PMC, 2019-09-27)
STRING: known and predicted protein-protein associations, integrated and transferred across organisms. [PMID: 15608232]
Christian von Mering, Lars J Jensen, Berend Snel, Sean D Hooper, Markus Krupp, Mathilde Foglierini, Nelly Jouffre, Martijn A Huynen, Peer Bork
A full description of a protein's function requires knowledge of all partner proteins with which it specifically associates. From a functional perspective, 'association' can mean direct physical binding, but can also mean indirect interaction such as participation in the same metabolic pathway or cellular process. Currently, information about protein association is scattered over a wide variety of resources and model organisms. STRING aims to simplify access to this information by providing a comprehensive, yet quality-controlled collection of protein-protein associations for a large number of organisms. The associations are derived from high-throughput experimental data, from the mining of databases and literature, and from predictions based on genomic context analysis. STRING integrates and ranks these associations by benchmarking them against a common reference set, and presents evidence in a consistent and intuitive web interface. Importantly, the associations are extended beyond the organism in which they were originally described, by automatic transfer to orthologous protein pairs in other organisms, where applicable. STRING currently holds 730,000 proteins in 180 fully sequenced organisms, and is available at http://string.embl.de/.
Nucleic Acids Res 2005:33(Database issue)
482 Citations (from Europe PMC, 2019-09-27)
STRING: a database of predicted functional associations between proteins. [PMID: 12519996]
Christian von Mering, Martijn Huynen, Daniel Jaeggi, Steffen Schmidt, Peer Bork, Berend Snel
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/.
Nucleic Acids Res 2003:31(1)
537 Citations (from Europe PMC, 2019-09-27)
STRING: a web-server to retrieve and display the repeatedly occurring neighbourhood of a gene. [PMID: 10982861]
B Snel, G Lehmann, P Bork, M A Huynen
The repeated occurrence of genes in each other's neighbourhood on genomes has been shown to indicate a functional association between the proteins they encode. Here we introduce STRING (search tool for recurring instances of neighbouring genes), a tool to retrieve and display the genes a query gene repeatedly occurs with in clusters on the genome. The tool performs iterative searches and visualises the results in their genomic context. By finding the genomically associated genes for a query, it delineates a set of potentially functionally associated genes. The usefulness of STRING is illustrated with an example that suggests a functional context for an RNA methylase with unknown specificity.
Nucleic Acids Res 2000:28(18)
352 Citations (from Europe PMC, 2019-09-27)