Towards a unified open access dataset of molecular interactions

Porras, Pablo; Barrera, Elisabet; Bridge, Alan; del-Toro, Noemi; Cesareni, Gianni; Duesbury, Margaret; Hermjakob, Henning; Iannuccelli, Marta; Jurišica, Igor; Kotlyar, Max; Licata, Luana; Lovering, Ruth C.; Lynn, David J.; Meldal, Birgit; Nanduri, Bindu; Paneerselvam, Kalpana; Panni, Simona; Pastrello, Chiara; Pellegrini, Matteo; Perfetto, Livia; Rahimzadeh, Negin; Ratan, Prashansa; Ricard‐Blum, Sylvie; Salwiński, Łukasz; Shirodkar, Gautam; Shrivastava, Anjali; Orchard, Sandra

doi:10.1038/s41467-020-19942-z

Cited by 57 publications

(56 citation statements)

References 76 publications

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“…Several sources of interaction data were combined to build a comprehensive interactome of the lysyl oxidase family. Experimental data were collected by querying manually curated databases MatrixDB [ 37 , 38 , 39 , 40 ] and IMEx databases, including IntAct [ 41 , 42 , 43 ], manually curating additional interactions, querying the large BioPlex 2.0 [ 44 ] and 3.0 [ 35 ] datasets generated by large-scale affinity purification-mass spectrometry, and performing in vitro binding assays. Surface plasmon resonance imaging (SPRi) binding assays were first performed using the protein and glycosaminoglycan (GAG) arrays we developed [ 33 , 45 , 46 ] comprised of 44 different biomolecules to identify new extracellular and membrane partners of LOXL2, which plays a prominent role in cancer, and of its N-terminal scavenger receptor cysteine-rich domains (SRCR).…”

Section: Resultsmentioning

confidence: 99%

“…The LOX and LOXL interaction dataset will be freely available via MatrixDB web site ( ), the ECM interaction database we have created and we maintain [ 37 , 38 , 39 , 40 ], and via the dataset of the International Molecular Exchange consortium ( ) to which MatrixDB belongs [ 41 , 43 ].…”

Section: Resultsmentioning

confidence: 99%

“…Interactions of LOX and LOXLs were retrieved by manual curation of the literature and by querying manually curated interaction databases including the database we created, MatrixDB ( , [ 37 , 38 , 39 , 40 ]), and IntAct [ 42 ]. Both databases belong to the International Molecular Exchange (IMEx) consortium and follow its curation rules to capture interaction data [ 41 , 43 ]. Interaction partners of LOX and LOXLs were also identified in BioPlex 2.0 and 3.0 datasets [ 35 , 44 ] generated by affinity chromatography-mass spectrometry (AP-MS) profiling the entire human ORFeome collection in human embryonic kidney cells (HEK 293) and in a human colon cancer cell line (HCT 116).…”

Section: Methodsmentioning

confidence: 99%

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The Interactome of Cancer-Related Lysyl Oxidase and Lysyl Oxidase-Like Proteins

Vallet

Berthollier

Salza

et al. 2020

Cancers

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The members of the lysyl oxidase (LOX) family are amine oxidases, which initiate the covalent cross-linking of the extracellular matrix (ECM), regulate ECM stiffness, and contribute to cancer progression. The aim of this study was to build the first draft of the interactome of the five members of the LOX family in order to determine its molecular functions, the biological and signaling pathways mediating these functions, the biological processes it is involved in, and if and how it is rewired in cancer. In vitro binding assays, based on surface plasmon resonance and bio-layer interferometry, combined with queries of interaction databases and interaction datasets, were used to retrieve interaction data. The interactome was then analyzed using computational tools. We identified 31 new interactions and 14 new partners of LOXL2, including the α5β1 integrin, and built an interactome comprising 320 proteins, 5 glycosaminoglycans, and 399 interactions. This network participates in ECM organization, degradation and cross-linking, cell-ECM interactions mediated by non-integrin and integrin receptors, protein folding and chaperone activity, organ and blood vessel development, cellular response to stress, and signal transduction. We showed that this network is rewired in colorectal carcinoma, leading to a switch from ECM organization to protein folding and chaperone activity.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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The Interactome of Cancer-Related Lysyl Oxidase and Lysyl Oxidase-Like Proteins

Vallet

Berthollier

Salza

et al. 2020

Cancers

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“…Through Rhea and ChEBI, UniProtKB provides a platform to integrate knowledge of small molecule metabolites, including but not limited to natural products, with knowledge of protein sequences and their functions in a broad range of species. Expert-curated knowledge of protein function in UniProtKB/Swiss-Prot is complemented by additional knowledge and links from a wide network of collaborating resources covering many aspects of protein biology, including InterPro (protein domains and families) [ 34 ], PDBe (protein structures) [ 35 ], Reactome (pathways) [ 36 ], the IMEx databases of molecular interactions [ 37 ], the Gene Ontology Consortium (additional GO annotations) [ 38 , 39 ], PubMed literature ( ), and many more. Researchers in the field of natural products can leverage these additional annotations, links, and integrated datasets to study a broad array of aspects of protein biology.…”

Section: Discussionmentioning

confidence: 99%

“…UniProtKB provides links to over 100 reference knowledgebases and data repositories, links that are exploited in our powerful identifier mapping and batch retrieval tool ( ). UniProtKB also integrates complementary data from many of these linked resources, including the aforementioned protein classifications from InterPro as well as others such as molecular interaction data from IMEx database [ 37 ], peptide data from ProteomeXchange database [ 54 ], and variation data from a range of clinical resources including ClinVar [ 55 ], COSMIC [ 56 ], 1000 Genomes [ 57 ], and dbSNP [ 58 ].…”

Section: Methodsmentioning

confidence: 99%

Diverse Taxonomies for Diverse Chemistries: Enhanced Representation of Natural Product Metabolism in UniProtKB

et al. 2021

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The UniProt Knowledgebase UniProtKB is a comprehensive, high-quality, and freely accessible resource of protein sequences and functional annotation that covers genomes and proteomes from tens of thousands of taxa, including a broad range of plants and microorganisms producing natural products of medical, nutritional, and agronomical interest. Here we describe work that enhances the utility of UniProtKB as a support for both the study of natural products and for their discovery. The foundation of this work is an improved representation of natural product metabolism in UniProtKB using Rhea, an expert-curated knowledgebase of biochemical reactions, that is built on the ChEBI (Chemical Entities of Biological Interest) ontology of small molecules. Knowledge of natural products and precursors is captured in ChEBI, enzyme-catalyzed reactions in Rhea, and enzymes in UniProtKB/Swiss-Prot, thereby linking chemical structure data directly to protein knowledge. We provide a practical demonstration of how users can search UniProtKB for protein knowledge relevant to natural products through interactive or programmatic queries using metabolite names and synonyms, chemical identifiers, chemical classes, and chemical structures and show how to federate UniProtKB with other data and knowledge resources and tools using semantic web technologies such as RDF and SPARQL. All UniProtKB data are freely available for download in a broad range of formats for users to further mine or exploit as an annotation source, to enrich other natural product datasets and databases.

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Building Protein‐Protein and Protein‐Glycosaminoglycan Interaction Networks Using MatrixDB, the Extracellular Matrix Interaction Database

et al. 2021

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The interaction database MatrixDB reports protein‐protein and protein‐glycosaminoglycan interactions in human, mammalian, and model organisms, involving at least one extracellular matrix (ECM) constituent, namely full‐length proteins, ECM multimeric proteins considered as stable complexes, proteoglycans, glycosaminoglycans (GAGs), and bioactive fragments called matricryptins, which are released upon limited proteolysis of ECM proteins. The current version of MatrixDB (as of October 2020) contains 106,543 experimentally supported interactions, with all types of biomolecules combined. MatrixDB is the only database focusing on the curation of ECM protein and GAG interactions. The iNavigator integrated in MatrixDB allows users to build interaction networks online and to filter them according to expression data, quantitative proteomics data, or interaction detection methods. MatrixDB belongs to the International Molecular Exchange (IMEx) consortium, and uses its curation rules to capture interaction data, which are available in standardized exchange formats according to the Human Proteome Organization—Proteomics Standards Initiative (HUPO‐PSI). © 2021 Wiley Periodicals LLC. Basic Protocol 1: Browse MatrixDB Basic Protocol 2: Create a list of biomolecules of interest to build interaction networks Basic Protocol 3: Build and export interaction networks of selected biomolecules using the iNavigator Basic Protocol 4: Build specific interaction networks using the iNavigator widgets Basic Protocol 5: Generate 3D models of glycosaminoglycan oligosaccharides using the GAG Builder tool

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Towards a unified open access dataset of molecular interactions

Cited by 57 publications

References 76 publications

The Interactome of Cancer-Related Lysyl Oxidase and Lysyl Oxidase-Like Proteins

The Interactome of Cancer-Related Lysyl Oxidase and Lysyl Oxidase-Like Proteins

Diverse Taxonomies for Diverse Chemistries: Enhanced Representation of Natural Product Metabolism in UniProtKB

Building Protein‐Protein and Protein‐Glycosaminoglycan Interaction Networks Using MatrixDB, the Extracellular Matrix Interaction Database

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