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The aim of the UniProt Knowledgebase is to provide users with a comprehensive, high-quality and freely accessible set of protein sequences annotated with functional information. In this article, we describe significant updates that we have made over the last two years to the resource. The number of sequences in UniProtKB has risen to approximately 190 million, despite continued work to reduce sequence redundancy at the proteome level. We have adopted new methods of assessing proteome completeness and quality. We continue to extract detailed annotations from the literature to add to reviewed entries and supplement these in unreviewed entries with annotations provided by automated systems such as the newly implemented Association-Rule-Based Annotator (ARBA). We have developed a credit-based publication submission interface to allow the community to contribute publications and annotations to UniProt entries. We describe how UniProtKB responded to the COVID-19 pandemic through expert curation of relevant entries that were rapidly made available to the research community through a dedicated portal. UniProt resources are available under a CC-BY (4.0) license via the web at https://www.uniprot.org/.

The Structure Integration with Function, Taxonomy and Sequences resource (SIFTS; http://pdbe.org/sifts/) was established in 2002 and continues to operate as a collaboration between the Protein Data Bank in Europe (PDBe; http://pdbe.org) and the UniProt Knowledgebase (UniProtKB; http://uniprot.org). The resource is instrumental in the transfer of annotations between protein structure and protein sequence resources through provision of up-to-date residue-level mappings between entries from the PDB and from UniProtKB. SIFTS also incorporates residue-level annotations from other biological resources, currently comprising the NCBI taxonomy database, IntEnz, GO, Pfam, InterPro, SCOP, CATH, PubMed, Ensembl, Homologene and automatic Pfam domain assignments based on HMM profiles. The recently released implementation of SIFTS includes support for multiple cross-references for proteins in the PDB, allowing mappings to UniProtKB isoforms and UniRef90 cluster members. This development makes structure data in the PDB readily available to over 1.8 million UniProtKB accessions.

The mission of the Universal Protein Resource (UniProt) (http://www.uniprot.org) is to provide the scientific community with a comprehensive, high-quality and freely accessible resource of protein sequences and functional annotation. It integrates, interprets and standardizes data from literature and numerous resources to achieve the most comprehensive catalog possible of protein information. The central activities are the biocuration of the UniProt Knowledgebase and the dissemination of these data through our Web site and web services. UniProt is produced by the UniProt Consortium, which consists of groups from the European Bioinformatics Institute (EBI), the SIB Swiss Institute of Bioinformatics (SIB) and the Protein Information Resource (PIR). UniProt is updated and distributed every 4 weeks and can be accessed online for searches or downloads.

The toxic component of amyloid is not the mature fiber but a soluble prefibrillar intermediate. It has been proposed, from molecular dynamics simulations, that the precursor is composed of alpha sheet, which converts into the beta sheet of mature amyloid via peptide plane flipping. alpha sheet, not seen in proteins, occurs as isolated stretches of polypeptide. We show that the alpha- to beta sheet transition can occur by the flipping of alternate peptide planes. The flip can be described as alphaRalphaL--betabeta. A search conducted within sets of closely related protein crystal structures revealed that these flips are common, occurring in 8.5% of protein families. The average "alphaL" conformation found is in an adjacent and less populated region of the Ramachandran plot, as expected if the flanking peptide planes, being hydrogen bonded, are restricted in their movements. This work provides evidence for flips allowing direct alpha- to beta sheet interconversion.

Background Increasingly large amounts of DNA sequencing data are being generated within the Wellcome Trust Sanger Institute (WTSI). The traditional file system struggles to handle these increasing amounts of sequence data. A good data management system therefore needs to be implemented and integrated into the current WTSI infrastructure. Such a system enables good management of the IT infrastructure of the sequencing pipeline and allows biologists to track their data. Results We have chosen a data grid system, iRODS (Rule-Oriented Data management systems), to act as the data management system for the WTSI. iRODS provides a rule-based system management approach which makes data replication much easier and provides extra data protection. Unlike the metadata provided by traditional file systems, the metadata system of iRODS is comprehensive and allows users to customize their own application level metadata. Users and IT experts in the WTSI can then query the metadata to find and track data. The aim of this paper is to describe how we designed and used (from both system and user viewpoints) iRODS as a data management system. Details are given about the problems faced and the solutions found when iRODS was implemented. A simple use case describing how users within the WTSI use iRODS is also introduced. Conclusions iRODS has been implemented and works as the production system for the sequencing pipeline of the WTSI. Both biologists and IT experts can now track and manage data, which could not previously be achieved. This novel approach allows biologists to define their own metadata and query the genomic data using those metadata.