Abstract
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. To extend our ability to annotate human disease processes, we have implemented a new drug class and have used it initially to annotate drugs relevant to cardiovascular disease. Our annotation model depends on external domain experts to identify new areas for annotation and to review new content. New web pages facilitate recruitment of community experts and allow those who have contributed to Reactome to identify their contributions and link them to their ORCID records. To improve visualization of our content, we have implemented a new tool to automatically lay out the components of individual reactions with multiple options for downloading the reaction diagrams and associated data, and a new display of our event hierarchy that will facilitate visual interpretation of pathway analysis results.
Abstract
It's widely appreciated that liquid–liquid phase separation (LLPS) underlies the formation of membraneless organelles, which function to concentrate proteins and nucleic acids. In the past ...few decades, major efforts have been devoted to identify the phase separation associated proteins and elucidate their functions. To better utilize the knowledge dispersed in published literature, we developed PhaSepDB (http://db.phasep.pro/), a manually curated database of phase separation associated proteins. Currently, PhaSepDB includes 2914 non-redundant proteins localized in different organelles curated from published literature and database. PhaSepDB provides protein summary, publication reference and sequence features of phase separation associated proteins. The sequence features which reflect the LLPS behavior are also available for other human protein candidates. The online database provides a convenient interface for the research community to easily browse, search and download phase separation associated proteins. As a centralized resource, we believe PhaSepDB will facilitate the future study of phase separation.
Reactome aims to provide bioinformatics tools for visualisation, interpretation and analysis of pathway knowledge to support basic research, genome analysis, modelling, systems biology and education. ...Pathway analysis methods have a broad range of applications in physiological and biomedical research; one of the main problems, from the analysis methods performance point of view, is the constantly increasing size of the data samples.
Here, we present a new high-performance in-memory implementation of the well-established over-representation analysis method. To achieve the target, the over-representation analysis method is divided in four different steps and, for each of them, specific data structures are used to improve performance and minimise the memory footprint. The first step, finding out whether an identifier in the user's sample corresponds to an entity in Reactome, is addressed using a radix tree as a lookup table. The second step, modelling the proteins, chemicals, their orthologous in other species and their composition in complexes and sets, is addressed with a graph. The third and fourth steps, that aggregate the results and calculate the statistics, are solved with a double-linked tree.
Through the use of highly optimised, in-memory data structures and algorithms, Reactome has achieved a stable, high performance pathway analysis service, enabling the analysis of genome-wide datasets within seconds, allowing interactive exploration and analysis of high throughput data. The proposed pathway analysis approach is available in the Reactome production web site either via the AnalysisService for programmatic access or the user submission interface integrated into the PathwayBrowser. Reactome is an open data and open source project and all of its source code, including the one described here, is available in the AnalysisTools repository in the Reactome GitHub ( https://github.com/reactome/ ).
The PRoteomics IDEntifications (PRIDE) database is one of the world-leading data repositories of mass spectrometry (MS)-based proteomics data. Since the beginning of 2014, PRIDE Archive ...(http://www.ebi.ac.uk/pride/archive/) is the new PRIDE archival system, replacing the original PRIDE database. Here we summarize the developments in PRIDE resources and related tools since the previous update manuscript in the Database Issue in 2013. PRIDE Archive constitutes a complete redevelopment of the original PRIDE, comprising a new storage backend, data submission system and web interface, among other components. PRIDE Archive supports the most-widely used PSI (Proteomics Standards Initiative) data standard formats (mzML and mzIdentML) and implements the data requirements and guidelines of the ProteomeXchange Consortium. The wide adoption of ProteomeXchange within the community has triggered an unprecedented increase in the number of submitted data sets (around 150 data sets per month). We outline some statistics on the current PRIDE Archive data contents. We also report on the status of the PRIDE related stand-alone tools: PRIDE Inspector, PRIDE Converter 2 and the ProteomeXchange submission tool. Finally, we will give a brief update on the resources under development 'PRIDE Cluster' and 'PRIDE Proteomes', which provide a complementary view and quality-scored information of the peptide and protein identification data available in PRIDE Archive.
Abstract
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. Reactome thus functions both as a digital archive of manually curated human biological processes and as a tool for discovering functional relationships in data such as gene expression profiles or somatic mutation catalogs from tumor cells. Recent curation work has expanded our annotations of normal and disease-associated signaling processes and of the drugs that target them, in particular infections caused by the SARS-CoV-1 and SARS-CoV-2 coronaviruses and the host response to infection. New tools support better simultaneous analysis of high-throughput data from multiple sources and the placement of understudied (‘dark’) proteins from analyzed datasets in the context of Reactome’s manually curated pathways.
Abstract
The ProteomeXchange (PX) consortium of proteomics resources (http://www.proteomexchange.org) has standardized data submission and dissemination of mass spectrometry proteomics data worldwide ...since 2012. In this paper, we describe the main developments since the previous update manuscript was published in Nucleic Acids Research in 2017. Since then, in addition to the four PX existing members at the time (PRIDE, PeptideAtlas including the PASSEL resource, MassIVE and jPOST), two new resources have joined PX: iProX (China) and Panorama Public (USA). We first describe the updated submission guidelines, now expanded to include six members. Next, with current data submission statistics, we demonstrate that the proteomics field is now actively embracing public open data policies. At the end of June 2019, more than 14 100 datasets had been submitted to PX resources since 2012, and from those, more than 9 500 in just the last three years. In parallel, an unprecedented increase of data re-use activities in the field, including ‘big data’ approaches, is enabling novel research and new data resources. At last, we also outline some of our future plans for the coming years.
Abstract
Motivation
Reactome is a free, open-source, open-data, curated and peer-reviewed knowledgebase of biomolecular pathways. For web-based pathway visualization, Reactome uses a custom pathway ...diagram viewer that has been evolved over the past years. Here, we present comprehensive enhancements in usability and performance based on extensive usability testing sessions and technology developments, aiming to optimize the viewer towards the needs of the community.
Results
The pathway diagram viewer version 3 achieves consistently better performance, loading and rendering of 97% of the diagrams in Reactome in less than 1 s. Combining the multi-layer html5 canvas strategy with a space partitioning data structure minimizes CPU workload, enabling the introduction of new features that further enhance user experience. Through the use of highly optimized data structures and algorithms, Reactome has boosted the performance and usability of the new pathway diagram viewer, providing a robust, scalable and easy-to-integrate solution to pathway visualization. As graph-based visualization of complex data is a frequent challenge in bioinformatics, many of the individual strategies presented here are applicable to a wide range of web-based bioinformatics resources.
Availability and implementation
Reactome is available online at: https://reactome.org. The diagram viewer is part of the Reactome pathway browser (https://reactome.org/PathwayBrowser/) and also available as a stand-alone widget at: https://reactome.org/dev/diagram/. The source code is freely available at: https://github.com/reactome-pwp/diagram.
Supplementary information
Supplementary data are available at Bioinformatics online.
The ProteomeXchange (PX) Consortium of proteomics resources (http://www.proteomexchange.org) was formally started in 2011 to standardize data submission and dissemination of mass spectrometry ...proteomics data worldwide. We give an overview of the current consortium activities and describe the advances of the past few years. Augmenting the PX founding members (PRIDE and PeptideAtlas, including the PASSEL resource), two new members have joined the consortium: MassIVE and jPOST. ProteomeCentral remains as the common data access portal, providing the ability to search for data sets in all participating PX resources, now with enhanced data visualization components.We describe the updated submission guidelines, now expanded to include four members instead of two. As demonstrated by data submission statistics, PX is supporting a change in culture of the proteomics field: public data sharing is now an accepted standard, supported by requirements for journal submissions resulting in public data release becoming the norm. More than 4500 data sets have been submitted to the various PX resources since 2012. Human is the most represented species with approximately half of the data sets, followed by some of the main model organisms and a growing list of more than 900 diverse species. Data reprocessing activities are becoming more prominent, with both MassIVE and PeptideAtlas releasing the results of reprocessed data sets. Finally, we outline the upcoming advances for ProteomeXchange.
Reactome is a free, open-source, open-data, curated and peer-reviewed knowledgebase of biomolecular pathways. One of its main priorities is to provide easy and efficient access to its high quality ...curated data. At present, biological pathway databases typically store their contents in relational databases. This limits access efficiency because there are performance issues associated with queries traversing highly interconnected data. The same data in a graph database can be queried more efficiently. Here we present the rationale behind the adoption of a graph database (Neo4j) as well as the new ContentService (REST API) that provides access to these data. The Neo4j graph database and its query language, Cypher, provide efficient access to the complex Reactome data model, facilitating easy traversal and knowledge discovery. The adoption of this technology greatly improved query efficiency, reducing the average query time by 93%. The web service built on top of the graph database provides programmatic access to Reactome data by object oriented queries, but also supports more complex queries that take advantage of the new underlying graph-based data storage. By adopting graph database technology we are providing a high performance pathway data resource to the community. The Reactome graph database use case shows the power of NoSQL database engines for complex biological data types.
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