Pathway-based, reaction-specific annotation of disease variants for elucidation of molecular phenotypes.

Germline and somatic mutations can give rise to proteins with altered activity, including both gain and loss-of-function. The effects of these variants can be captured in disease-specific reactions and pathways that highlight the resulting changes to normal biology. A disease reaction is defined as an aberrant reaction in which a variant protein participates.

ChatGPT usage in the Reactome curation process.

Appreciating the rapid advancement and ubiquity of generative AI, particularly ChatGPT, a chatbot using large language models like GPT, we endeavour to explore the potential application of ChatGPT in the data collection and annotation stages within the Reactome curation process. This exploration aimed to create an automated or semi-automated framework to mitigate the extensive manual effort traditionally required for gathering and annotating information pertaining to biological pathways, adopting a Reactome "reaction-centric" approach. In this pilot study, we used ChatGPT/GPT4 to address gaps in the pathway annotation and enrichment in parallel with the conventional manual curation process.

The Reactome Pathway Knowledgebase 2024.

The Reactome Knowledgebase (https://reactome.org), an Elixir and GCBR core biological data resource, provides manually curated molecular details of a broad range of normal and disease-related biological processes. Processes are annotated as an ordered network of molecular transformations in a single consistent data model.

Pathway-based, reaction-specific annotation of disease variants for elucidation of molecular phenotypes.

Disease variant annotation in the context of biological reactions and pathways can provide a standardized overview of molecular phenotypes of pathogenic mutations that is amenable to computational mining and mathematical modeling. Reactome, an open source, manually curated, peer-reviewed database of human biological pathways, provides annotations for over 4000 disease variants of close to 400 genes in the context of ∼800 disease reactions constituting ∼400 disease pathways. Functional annotation of disease variants proceeds from normal gene functions, through disease variants whose divergence from normal molecular behaviors has been experimentally verified, to extrapolation from molecular phenotypes of characterized variants to variants of unknown significance using criteria of the American College of Medical Genetics and Genomics (ACMG).

Using the Reactome Database.

Pathway databases provide descriptions of the roles of proteins, nucleic acids, lipids, carbohydrates, and other molecular entities within their biological cellular contexts. Pathway-centric views of these roles may allow for the discovery of unexpected functional relationships in data such as gene expression profiles and somatic mutation catalogues from tumor cells. For this reason, there is a high demand for high-quality pathway databases and their associated tools.

The reactome pathway knowledgebase 2022.

The Reactome Knowledgebase (https://reactome.org), an Elixir core resource, provides manually curated molecular details across a broad range of physiological and pathological biological processes in humans, including both hereditary and acquired disease processes. The processes are annotated as an ordered network of molecular transformations in a single consistent data model.

COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms.

We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources.

The reactome pathway knowledgebase.

The Reactome Knowledgebase (https://reactome.org) provides molecular details of signal transduction, transport, DNA replication, metabolism and other cellular processes as an ordered network of molecular transformations in a single consistent data model, an extended version of a classic metabolic map. Reactome functions both as an archive of biological processes and as a tool for discovering functional relationships in data such as gene expression profiles or somatic mutation catalogs from tumor cells.

Interleukins and their signaling pathways in the Reactome biological pathway database.

Background: There is a wealth of biological pathway information available in the scientific literature, but it is spread across many thousands of publications. Alongside publications that contain definitive experimental discoveries are many others that have been dismissed as spurious, found to be irreproducible, or are contradicted by later results and consequently now considered controversial. Many descriptions and images of pathways are incomplete stylized representations that assume the reader is an expert and familiar with the established details of the process, which are consequently not fully explained.

The Reactome Pathway Knowledgebase.

The Reactome Knowledgebase (https://reactome.org) provides molecular details of signal transduction, transport, DNA replication, metabolism, and other cellular processes as an ordered network of molecular transformations-an extended version of a classic metabolic map, in a single consistent data model. Reactome functions both as an archive of biological processes and as a tool for discovering unexpected functional relationships in data such as gene expression profiles or somatic mutation catalogues from tumor cells.

Reactome enhanced pathway visualization.

Motivation: Reactome is a free, open-source, open-data, curated and peer-reviewed knowledge base of biomolecular pathways. Pathways are arranged in a hierarchical structure that largely corresponds to the GO biological process hierarchy, allowing the user to navigate from high level concepts like immune system to detailed pathway diagrams showing biomolecular events like membrane transport or phosphorylation. Here, we present new developments in the Reactome visualization system that facilitate navigation through the pathway hierarchy and enable efficient reuse of Reactome visualizations for users' own research presentations and publications.

Protein Ontology (PRO): enhancing and scaling up the representation of protein entities.

The Protein Ontology (PRO; http://purl.obolibrary.org/obo/pr) formally defines and describes taxon-specific and taxon-neutral protein-related entities in three major areas: proteins related by evolution; proteins produced from a given gene; and protein-containing complexes.

The Reactome pathway Knowledgebase.

The Reactome Knowledgebase (www.reactome.org) provides molecular details of signal transduction, transport, DNA replication, metabolism and other cellular processes as an ordered network of molecular transformations-an extended version of a classic metabolic map, in a single consistent data model.

Toll-like receptor signaling in vertebrates: testing the integration of protein, complex, and pathway data in the protein ontology framework.

The Protein Ontology (PRO) provides terms for and supports annotation of species-specific protein complexes in an ontology framework that relates them both to their components and to species-independent families of complexes. Comprehensive curation of experimentally known forms and annotations thereof is expected to expose discrepancies, differences, and gaps in our knowledge. We have annotated the early events of innate immune signaling mediated by Toll-Like Receptor 3 and 4 complexes in human, mouse, and chicken.

Protein Ontology: a controlled structured network of protein entities.

The Protein Ontology (PRO; http://proconsortium.org) formally defines protein entities and explicitly represents their major forms and interrelations. Protein entities represented in PRO corresponding to single amino acid chains are categorized by level of specificity into family, gene, sequence and modification metaclasses, and there is a separate metaclass for protein complexes.

The Reactome pathway knowledgebase.

Reactome (http://www.reactome.org) is a manually curated open-source open-data resource of human pathways and reactions.

Reactome: a database of reactions, pathways and biological processes.

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.

Human and chicken TLR pathways: manual curation and computer-based orthology analysis.

The innate immune responses mediated by Toll-like receptors (TLR) provide an evolutionarily well-conserved first line of defense against microbial pathogens. In the Reactome Knowledgebase we previously integrated annotations of human TLR molecular functions with those of over 4000 other human proteins involved in processes such as adaptive immunity, DNA replication, signaling, and intermediary metabolism, and have linked these annotations to external resources, including PubMed, UniProt, EntrezGene, Ensembl, and the Gene Ontology to generate a resource suitable for data mining, pathway analysis, and other systems biology approaches. We have now used a combination of manual expert curation and computer-based orthology analysis to generate a set of annotations for TLR molecular function in the chicken (Gallus gallus).