BioPAX (Biological Pathway Exchange) is a RDF / OWL -based standard language to represent biological pathways at the molecular and cellular level. Its major use is to facilitate the exchange of pathway data. Pathway data captures our understanding of biological processes, but its rapid growth necessitates development of databases and computational tools to aid interpretation. However, the current fragmentation of pathway information across many databases with incompatible formats presents barriers to its effective use. BioPAX solves this problem by making pathway data substantially easier to collect, index, interpret and share. BioPAX can represent metabolic and signaling pathways, molecular and genetic interactions and gene regulation networks. BioPAX was created through a community process. Through BioPAX, millions of interactions organized into thousands of pathways across many organisms, from a growing number of sources, are available. Thus, large amounts of pathway data are available in a computable form to support visualization, analysis and biological discovery.
36-427: It is supported by a variety of online databases (e.g. Reactome ) and tools. The latest released version is BioPAX Level 3. There is also an effort to create a version of BioPAX as part of OBO . The next version of BioPAX, Level 4, is being developed by a community of researchers. Development is coordinated by the board of editors and facilitated by various BioPAX work groups. Systems Biology Pathway Exchange (SBPAX)
72-405: A high level of annotation (such as the description of the function of a protein, its domain structure, post-translational modifications , variants, etc.), a minimal level of redundancy and high level of integration with other databases. Recognizing that sequence data were being generated at a pace exceeding Swiss-Prot's ability to keep up, TrEMBL (Translated EMBL Nucleotide Sequence Data Library)
108-426: A list of statistically over-represented pathways. Expression data is submitted in a multi-column format, the first column identifying the protein, additional columns are expected to be numeric expression values, they can in fact be any numeric value, e.g. differential expression, quantitative proteomics, GWAS scores. The expression data is represented as colouring of the corresponding proteins in pathway diagrams, using
144-492: A network of biological interactions and are grouped into pathways. Examples of biological pathways in Reactome include signal transduction , innate and acquired immune function, transcriptional regulation , programmed cell death and classical intermediary metabolism . The pathways represented in Reactome are species-specific, with each pathway step supported by literature citations that contain an experimental verification of
180-525: A representative protein, the accession numbers of all the merged entries and links to the corresponding UniProtKB and UniParc records are displayed. UniRef100 sequences are clustered using the CD-HIT algorithm to build UniRef90 and UniRef50. Each cluster is composed of sequences that have at least 90% or 50% sequence identity, respectively, to the longest sequence. Clustering sequences significantly reduces database size, enabling faster sequence searches. UniRef
216-493: A set of genes, visualize hit pathways, and investigate functional relationships among genes in hit pathways. The app also accesses the Reactome Functional Interaction (FI) network. There are several Reactomes that concentrate on specific organisms, the largest of these is focused on human biology , described on this page. See Plant Reactome. Other molecular pathway databases UniProt UniProt
252-440: A suite of data analysis tools. The underlying data is fully downloadable in a number of standard formats including PDF , SBML , Neo4j GraphDB, MySQL, PSI-MITAB, and BioPAX . Pathway diagrams use a Process Description (PD) Systems Biology Graphical Notation ( SBGN )-based style. The core unit of the Reactome data model is the reaction. Entities (nucleic acids, proteins, complexes and small molecules) participating in reactions form
288-467: A variety of formats including PDF, BioPAX , and SBML Reactome also has a ReactomeGSA tool, integrated into the Reactome Analysis Tools that allows comparative pathway analyses of multi-omics datasets, with compatibility with single-cell RNA-seq data. Public data from EBI Expression Atlas, Single Cell Expression Atlas, and NCBI GREIN GEO data can be integrated into the analysis. ReactomeGSA
324-443: Is a comprehensive and non-redundant database, which contains all the protein sequences from the main, publicly available protein sequence databases. Proteins may exist in several different source databases, and in multiple copies in the same database. In order to avoid redundancy, UniParc stores each unique sequence only once. Identical sequences are merged, regardless of whether they are from the same or different species. Each sequence
360-422: Is a free online database of biological pathways . It is manually curated and authored by PhD-level biologists, in collaboration with Reactome editorial staff. The content is cross-referenced to many bioinformatics databases. The rationale behind Reactome is to visually represent biological pathways in full mechanistic detail, while making the source data available in a computationally accessible format. Reactome
396-507: Is a freely accessible database of protein sequence and functional information, many entries being derived from genome sequencing projects . It contains a large amount of information about the biological function of proteins derived from the research literature. It is maintained by the UniProt consortium, which consists of several European bioinformatics organisations and a foundation from Washington, DC , USA . The UniProt consortium comprises
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#1732902788181432-424: Is a manually annotated, non-redundant protein sequence database. It combines information extracted from scientific literature and biocurator -evaluated computational analysis. The aim of UniProtKB/Swiss-Prot is to provide all known relevant information about a particular protein. Annotation is regularly reviewed to keep up with current scientific findings. The manual annotation of an entry involves detailed analysis of
468-558: Is a protein database partially curated by experts, consisting of two sections: UniProtKB/Swiss-Prot (containing reviewed, manually annotated entries) and UniProtKB/TrEMBL (containing unreviewed, automatically annotated entries). As of 22 February 2023 , release "2023_01" of UniProtKB/Swiss-Prot contains 569,213 sequence entries (comprising 205,728,242 amino acids abstracted from 291,046 references) and release "2023_01" of UniProtKB/TrEMBL contains 245,871,724 sequence entries (comprising 85,739,380,194 amino acids). UniProtKB/Swiss-Prot
504-411: Is also available as a R Bioconductor package . Reactome also has a ReactomeIDG web portal, since 2023, aimed to place dark proteins in the context of manually curated, highly reliable Reactome pathways, to facilitate the understanding of functions and predicting therapeutic potential of dark or understudied proteins. Enhanced visualization features implemented at the portal allow users to investigate
540-669: Is an extension for Level 3 and proposal for Level 4 to add quantitative data and systems biology terms (such as Systems Biology Ontology ). SBPAX export has been implemented by the pathway databases Signaling Gateway Molecule Pages , and the SABIO-Reaction Kinetics Database . SBPAX import has been implemented by the cellular modeling framework Virtual Cell . Other proposals for Level 4 include improved support for Semantic Web , validation and visualization. Online databases offering BioPAX export include: Software supporting BioPAX include: Reactome Reactome
576-403: Is archived. Currently UniParc contains protein sequences from the following publicly available databases: The UniProt Reference Clusters (UniRef) consist of three databases of clustered sets of protein sequences from UniProtKB and selected UniParc records. The UniRef100 database combines identical sequences and sequence fragments (from any organism ) into a single UniRef entry. The sequence of
612-481: Is freely available for download in several data and image formats. Reactome is completely open access and open source . Usage of Reactome material is covered by two Creative Commons licenses. The terms of the Creative Commons Public Domain (CC0) License apply to all Reactome annotation files, e.g. identifier mapping data, specialized data files, and interaction data derived from Reactome. The terms of
648-481: Is given a stable and unique identifier (UPI), making it possible to identify the same protein from different source databases. UniParc contains only protein sequences, with no annotation. Database cross-references in UniParc entries allow further information about the protein to be retrieved from the source databases. When sequences in the source databases change, these changes are tracked by UniParc and history of all changes
684-539: Is maintained by an international multidisciplinary team from OICR, OHSU, EMBL-EBI and NYULMC, with expertise in pathway curation and annotation, software development, and training and outreach, dedicated to providing the research community with openly accessible biological pathway knowledge. The Reactome team is led by Lincoln Stein (OICR). Peter D'Eustachio (NYULMC), Henning Hermjakob (EMBL-EBI), Guanming Wu (OHSU). The Reactome helpdesk can be reached via email . The website can be used to browse pathways and submit data to
720-415: Is read, and information is extracted and added to the entry. Annotation arising from the scientific literature includes, but is not limited to: Annotated entries undergo quality assurance before inclusion into UniProtKB/Swiss-Prot. When new data becomes available, entries are updated. UniProtKB/TrEMBL contains high-quality computationally analyzed records, which are enriched with automatic annotation. It
756-450: Is used in the annotation of UniProtKB/Swiss-Prot entries. Computer-predictions are manually evaluated, and relevant results selected for inclusion in the entry. These predictions include post-translational modifications, transmembrane domains and topology , signal peptides , domain identification, and protein family classification. Relevant publications are identified by searching databases such as PubMed . The full text of each paper
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#1732902788181792-928: The European Bioinformatics Institute (EBI), the Swiss Institute of Bioinformatics (SIB), and the Protein Information Resource (PIR). EBI, located at the Wellcome Trust Genome Campus in Hinxton, UK, hosts a large resource of bioinformatics databases and services. SIB, located in Geneva, Switzerland, maintains the ExPASy (Expert Protein Analysis System) servers that are a central resource for proteomics tools and databases. PIR, hosted by
828-466: The calendar of annotation projects . Reactome invites biological experts as reviewers for completed pathways that are ready for external review. Reviewers will be credited with authorship or reviewership for contributions. Each pathway is associated with a DOI and can be cited as a publication. Reactome contributions in can be easily claimed using the ORCID claiming feature. The pathway content at Reactome
864-692: The Creative Commons Attribution 4.0 International (CC BY 4.0) License apply to all software and code, e.g. relating to the functionality of the reactome.org, derived websites and webservices, the Curator Tool, the Functional Interaction application, SQL and Graph Database data dumps, and Pathway Illustrations (Enhanced High-Level Diagrams), Icon Library, Art and Branding Materials. Reactome can be cited using their major publications or by individual pathways or images. There are tools on
900-727: The National Biomedical Research Foundation (NBRF) at the Georgetown University Medical Center in Washington, DC, US, is heir to the oldest protein sequence database, Margaret Dayhoff 's Atlas of Protein Sequence and Structure, first published in 1965. In 2002, EBI, SIB, and PIR joined forces as the UniProt consortium. Each consortium member is heavily involved in protein database maintenance and annotation. Until recently, EBI and SIB together produced
936-603: The Swiss-Prot and TrEMBL databases, while PIR produced the Protein Sequence Database (PIR-PSD). These databases coexisted with differing protein sequence coverage and annotation priorities. Swiss-Prot was created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and subsequently developed by Rolf Apweiler at the European Bioinformatics Institute . Swiss-Prot aimed to provide reliable protein sequences associated with
972-471: The classical chemical interconversions of intermediary metabolism, binding events, complex formation, transport events that direct molecules between cellular compartments, and events such as the activation of a protein by cleavage of one or more of its peptide bonds. Individual events can be grouped together into pathways. Physical entities can be small molecules like glucose or ATP, or large molecules like DNA, RNA, and proteins, encoded directly or indirectly in
1008-425: The colours of the visible spectrum so 'hot' red colours represent high values. If multiple columns of numeric data are submitted the overlay tool can display them as separate 'experiments', e.g. timepoints or a disease progression. The database can be browsed and searched as an on-line textbook. An online users guide is available . Users can also download the current data set or individual pathways and reactions in
1044-491: The functional contexts for dark proteins based on tissue-specific gene or protein expression, drug-target interactions, or protein or gene pairwise relationships in the original Reactome's systems biology graph notation (SBGN) diagrams or the new simplified functional interaction (FI) network view of pathways. ReactomeFIViz is a Cytoscape app designed to find pathways and network patterns related to diseases. The app accesses Reactome pathways, perform pathway enrichment analysis for
1080-590: The human genome. Physical entities are cross-referenced to relevant external databases, such as UniProt for proteins and ChEBI for small molecules. Localization of molecules to subcellular compartments is a key feature of the regulation of human biological processes, so molecules in the Reactome database are associated with specific locations. Thus in Reactome instances of the same chemical entity in different locations (e.g., extracellular glucose and cytosolic glucose) are treated as distinct chemical entities. The Gene Ontology controlled vocabularies are used to describe
1116-847: The process represented. If no experimental verification using human reagents exists, pathways may contain steps manually inferred from non-human experimental details, but only if an expert biologist, named as Author of the pathway, and a second biologist, names as Reviewer, agree that this is a valid inference to make. The human pathways are used to computationally generate by an orthology-based process derived pathways in other organisms . Reactome database releases occur quarterly. In Reactome, human biological processes are annotated by breaking them down into series of molecular events. Like classical chemistry reactions each Reactome event has input physical entities (substrates) which interact, possibly facilitated by enzymes or other molecular catalysts, to generate output physical entities (products). Reactions include
BioPAX - Misplaced Pages Continue
1152-417: The protein sequence and of the scientific literature. Sequences from the same gene and the same species are merged into the same database entry. Differences between sequences are identified, and their cause documented (for example alternative splicing , natural variation , incorrect initiation sites, incorrect exon boundaries, frameshifts , unidentified conflicts). A range of sequence analysis tools
1188-401: The subcellular locations of molecules and reactions, molecular functions, and the larger biological processes that a specific reaction is part of. The database contains curated annotations that cover a diverse set of topics in molecular and cellular biology . Details of annotation topics can be found in the table of contents . Details of current and future annotation projects can be found in
1224-485: The website for viewing an interactive pathway diagram, performing pathway mapping and pathway over-representation analysis and for overlaying expression data onto Reactome pathways. The pathway mapping and over-representation tools take a single column of protein/compound identifiers, Uniprot and ChEBI accessions are preferred but the interface will accept and interpret many other identifiers or symbols. Mixed identifiers can be used. Over-representation results are presented as
1260-593: Was created to provide automated annotations for those proteins not in Swiss-Prot. Meanwhile, PIR maintained the PIR-PSD and related databases, including iProClass , a database of protein sequences and curated families. The consortium members pooled their overlapping resources and expertise, and launched UniProt in December 2003. UniProt provides four core databases: UniProtKB (with sub-parts Swiss-Prot and TrEMBL), UniParc, UniRef and Proteome. UniProt Knowledgebase (UniProtKB)
1296-751: Was introduced in response to increased dataflow resulting from genome projects, as the time- and labour-consuming manual annotation process of UniProtKB/Swiss-Prot could not be broadened to include all available protein sequences. The translations of annotated coding sequences in the EMBL-Bank/GenBank/DDBJ nucleotide sequence database are automatically processed and entered in UniProtKB/TrEMBL. UniProtKB/TrEMBL also contains sequences from PDB , and from gene prediction, including Ensembl , RefSeq and CCDS . Since 22 July 2021 it also includes structures predicted with AlphaFold2 . UniProt Archive (UniParc)
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