The PRoteomics IDEntifications (PRIDE, http://www.ebi.ac.uk/pride) database at the European Bioinformatics Institute is one of the most prominent data repositories of mass spectrometry (MS)-based proteomics data. Here, we summarize recent developments in the PRIDE database and related tools. First, we provide up-to-date statistics in data content, splitting the figures by groups of organisms and species, including peptide and protein identifications, and post-translational modifications. We then describe the tools that are part of the PRIDE submission pipeline, especially the recently developed PRIDE Converter 2 (new submission tool) and PRIDE Inspector (visualization and analysis tool). We also give an update about the integration of PRIDE with other MS proteomics resources in the context of the ProteomeXchange consortium. Finally, we briefly review the quality control efforts that are ongoing at present and outline our future plans.

Reactome (http://www.reactome.org) is a collaboration among groups at the Ontario Institute for Cancer Research, Cold Spring Harbor Laboratory, New York University School of Medicine and The European Bioinformatics Institute, to develop an open source curated bioinformatics database of human pathways and reactions. Recently, we developed a new web site with improved tools for pathway browsing and data analysis. The Pathway Browser is an Systems Biology Graphical Notation (SBGN)-based visualization system that supports zooming, scrolling and event highlighting. It exploits PSIQUIC web services to overlay our curated pathways with molecular interaction data from the Reactome Functional Interaction Network and external interaction databases such as IntAct, BioGRID, ChEMBL, iRefIndex, MINT and STRING. Our Pathway and Expression Analysis tools enable ID mapping, pathway assignment and overrepresentation analysis of user-supplied data sets. To support pathway annotation and analysis in other species, we continue to make orthology-based inferences of pathways in non-human species, applying Ensembl Compara to identify orthologs of curated human proteins in each of 20 other species. The resulting inferred pathway sets can be browsed and analyzed with our Species Comparison tool. Collaborations are also underway to create manually curated data sets on the Reactome framework for chicken, Drosophila and rice.

To study proteins in the context of a cellular system, it is essential that the molecules with which a protein interacts are identified and the functional consequence of each interaction is understood. A plethora of resources now exist to capture molecular interaction data from the many laboratories generating

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Toll-like receptors (TLR) play a key role in the innate immune system, providing vertebrates with a critical first line of defense against invading microbial pathogens. With the increasing body of molecular data relating to TLR function, organizing this information is useful to biologists and immunologists. We have used Reactome (www.reactome.org), a manually curated pathway database, to organize TLR data so that it can be viewed like an electronic textbook. TLR signaling cascades were authored by experts, maintained by the Reactome editorial staff and cross-referenced to publicly available bioinformatics resources. The Reactome data model generalizes the concept of a biochemical reaction to encompass any transformation of an input set of physical entities into an output set, and thus allows us to integrate TLR cascades with other innate immune processes, adaptive immunity, metabolic pathways, and other signaling processes. Since TLR-signaling molecules and pathways and the signaling pathways they initiate are highly conserved, Reactome provides pathway inference for 22 species based upon improved orthology prediction methods. A new entity-level pathway viewer and pathway analysis tools facilitate searching and visualizing pathway data and the analysis of user-supplied high-throughput data sets. All data content and software can be freely used and redistributed under open source terms.

Reactome ("http://www.reactome.org":http://www.reactome.org) is an expert-authored, peer-reviewed knowledgebase of human reactions and pathways that functions as a data mining resource and electronic textbook. Its current release includes 2921 human proteins, 2871 reactions and 4167 literature citations. This curated dataset is integrated with a functional interaction network assembled computationally from non-curated sources of information including protein-protein interactions, gene co-expression, and gene ontology annotations, providing access. A new entity-level pathway viewer and improved search and data mining tools facilitate searching and visualizing pathway data and the analysis of user-supplied high-throughput data sets. Reactome has increased its utility to the model organism communities with improved orthology prediction methods allowing pathway inference for 22 species and through collaborations to create manually curated Reactome pathway datasets for species including Arabidopsis, Oryza sativa (rice), Drosophila and Gallus gallus (chicken). Reactome's data content and software can all be freely used and redistributed under open source terms. Reactome instances are cross-referenced to corresponding ones in databases including EntrezGene, OMIM, Ensembl, UniProt, the UCSC Genome Browser, KEGG, ChEBI, and Gene Ontology.

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