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      Minimizing proteome redundancy in the UniProt Knowledgebase

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          Abstract

          Advances in high-throughput sequencing have led to an unprecedented growth in genome sequences being submitted to biological databases. In particular, the sequencing of large numbers of nearly identical bacterial genomes during infection outbreaks and for other large-scale studies has resulted in a high level of redundancy in nucleotide databases and consequently in the UniProt Knowledgebase (UniProtKB). Redundancy negatively impacts on database searches by causing slower searches, an increase in statistical bias and cumbersome result analysis. The redundancy combined with the large data volume increases the computational costs for most reuses of UniProtKB data. All of this poses challenges for effective discovery in this wealth of data. With the continuing development of sequencing technologies, it is clear that finding ways to minimize redundancy is crucial to maintaining UniProt's essential contribution to data interpretation by our users. We have developed a methodology to identify and remove highly redundant proteomes from UniProtKB. The procedure identifies redundant proteomes by performing pairwise alignments of sets of sequences for pairs of proteomes and subsequently, applies graph theory to find dominating sets that provide a set of non-redundant proteomes with a minimal loss of information. This method was implemented for bacteria in mid-2015, resulting in a removal of 50 million proteins in UniProtKB. With every new release, this procedure is used to filter new incoming proteomes, resulting in a more scalable and scientifically valuable growth of UniProtKB.

          Database URL: http://www.uniprot.org/proteomes/

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          Most cited references11

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          Comparison of 61 Sequenced Escherichia coli Genomes

          Escherichia coli is an important component of the biosphere and is an ideal model for studies of processes involved in bacterial genome evolution. Sixty-one publically available E. coli and Shigella spp. sequenced genomes are compared, using basic methods to produce phylogenetic and proteomics trees, and to identify the pan- and core genomes of this set of sequenced strains. A hierarchical clustering of variable genes allowed clear separation of the strains into clusters, including known pathotypes; clinically relevant serotypes can also be resolved in this way. In contrast, when in silico MLST was performed, many of the various strains appear jumbled and less well resolved. The predicted pan-genome comprises 15,741 gene families, and only 993 (6%) of the families are represented in every genome, comprising the core genome. The variable or ‘accessory’ genes thus make up more than 90% of the pan-genome and about 80% of a typical genome; some of these variable genes tend to be co-localized on genomic islands. The diversity within the species E. coli, and the overlap in gene content between this and related species, suggests a continuum rather than sharp species borders in this group of Enterobacteriaceae.
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            PISCES: recent improvements to a PDB sequence culling server

            PISCES is a database server for producing lists of sequences from the Protein Data Bank (PDB) using a number of entry- and chain-specific criteria and mutual sequence identity. Our goal in culling the PDB is to provide the longest list possible of the highest resolution structures that fulfill the sequence identity and structural quality cut-offs. The new PISCES server uses a combination of PSI-BLAST and structure-based alignments to determine sequence identities. Structure alignment produces more complete alignments and therefore more accurate sequence identities than PSI-BLAST. PISCES now allows a user to cull the PDB by-entry in addition to the standard culling by individual chains. In this scenario, a list will contain only entries that do not have a chain that has a sequence identity to any chain in any other entry in the list over the sequence identity cut-off. PISCES also provides fully annotated sequences including gene name and species. The server allows a user to cull an input list of entries or chains, so that other criteria, such as function, can be used. Results from a search on the re-engineered RCSB's site for the PDB can be entered into the PISCES server by a single click, combining the powerful searching abilities of the PDB with PISCES's utilities for sequence culling. The server's data are updated weekly. The server is available at .
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              A Year of Infection in the Intensive Care Unit: Prospective Whole Genome Sequencing of Bacterial Clinical Isolates Reveals Cryptic Transmissions and Novel Microbiota

              Bacterial whole genome sequencing holds promise as a disruptive technology in clinical microbiology, but it has not yet been applied systematically or comprehensively within a clinical context. Here, over the course of one year, we performed prospective collection and whole genome sequencing of nearly all bacterial isolates obtained from a tertiary care hospital’s intensive care units (ICUs). This unbiased collection of 1,229 bacterial genomes from 391 patients enables detailed exploration of several features of clinical pathogens. A sizable fraction of isolates identified as clinically relevant corresponded to previously undescribed species: 12% of isolates assigned a species-level classification by conventional methods actually qualified as distinct, novel genomospecies on the basis of genomic similarity. Pan-genome analysis of the most frequently encountered pathogens in the collection revealed substantial variation in pan-genome size (1,420 to 20,432 genes) and the rate of gene discovery (1 to 152 genes per isolate sequenced). Surprisingly, although potential nosocomial transmission of actively surveilled pathogens was rare, 8.7% of isolates belonged to genomically related clonal lineages that were present among multiple patients, usually with overlapping hospital admissions, and were associated with clinically significant infection in 62% of patients from which they were recovered. Multi-patient clonal lineages were particularly evident in the neonatal care unit, where seven separate Staphylococcus epidermidis clonal lineages were identified, including one lineage associated with bacteremia in 5/9 neonates. Our study highlights key differences in the information made available by conventional microbiological practices versus whole genome sequencing, and motivates the further integration of microbial genome sequencing into routine clinical care.
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                Author and article information

                Journal
                Database (Oxford)
                Database (Oxford)
                databa
                databa
                Database: The Journal of Biological Databases and Curation
                Oxford University Press
                1758-0463
                2016
                26 December 2016
                26 December 2016
                : 2016
                : baw139
                Affiliations
                [1 ]European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK
                [2 ]SIB Swiss Institute of Bioinformatics, Centre Medical Universitaire, 1 rue Michel Servet, Geneva 4 1211, Switzerland
                Author notes
                [* ]Corresponding author: Tel: +44 (0)1223 494 408; Fax: +44 (0)1223 494 468; E-mail: martin@ 123456ebi.ac.uk

                Citation details: Bursteinas, B., Britto, R., Bely, B. et al. Minimizing proteome redundancy in the UniProt Knowledgebase. Database (2016) Vol. 2016: article ID baw139; doi:10.1093/database/baw139

                Article
                baw139
                10.1093/database/baw139
                5199198
                28025334
                c0ca77c2-2763-4e8c-ae51-eb591d3935fd
                © The Author(s) 2016. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 08 August 2016
                : 22 September 2016
                : 23 September 2016
                Page count
                Pages: 9
                Categories
                Original Article

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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