neXtProt: a knowledge platform for human proteins

Abstract

neXtProt (http://www.nextprot.org/) is a new human protein-centric knowledge platform. Developed at the Swiss Institute of Bioinformatics (SIB), it aims to help researchers answer questions relevant to human proteins. To achieve this goal, neXtProt is built on a corpus containing both curated knowledge originating from the UniProtKB/Swiss-Prot knowledgebase and carefully selected and filtered high-throughput data pertinent to human proteins. This article presents an overview of the database and the data integration process. We also lay out the key future directions of neXtProt that we consider the necessary steps to make neXtProt the one-stop-shop for all research projects focusing on human proteins.

Figure 1.

The neXtProt home page grants access to the database via a search tool. Users can sign-in (top right) to create a personal account that allows them to personalize their usage of the platform by keeping a history of their queries and favoring or tagging search results. The home page also links to pages with more information about the current content of the platform in term of integrated resources (‘release details’ link at the bottom right).

Figure 2.

The Search Results page. neXtProt is indexed across several biological areas, corresponding to the different views found on each entry (some data are present in multiple indexes). This allows users to make complex searches, for example finding all proteins localized to the lysosomes and expressed in the brain. From the search results page, it is possible to do various exports: obtain the list of proteins as an Excel file; the protein sequences as FASTA or PEFF, or the entire entry in XML format. When a user is logged in, checkboxes appear next to each entry, so that s/he is able to select specific entries for which the data are exported.

Figure 3.

The Expression Data view displays data via a browser of the neXtProt human anatomy ontology. Currently, the data presented come from two different sources: Bgee and HPA (see text). Data are captured and displayed at the original granularity level (Loupe symbols), and is propagated to higher levels using the ontology to be comparable across the data sets. The tool provides a menu to toggle between showing only Gold data and showing both Gold and Silver data. An icon next to the annotation indicates the silver data. Unmarked data is gold.

Figure 4.

The Sequence Viewer, accessible from the Sequence view, displays - in addition to the sequence itself, the different features of the sequence (processing, regions, modified residues, topological information, variants, sequence conflicts, etc.) as a graphical overview and a table view. When a feature is selected, either from the graphical viewer or from the feature table, the corresponding sequence is immediately highlighted on the right. The sequence viewer also provides direct access to the BLAST tool, which has the option of using the full sequence, a selection corresponding to a sequence feature or any other sub-sequence selected by the user.

Figure 5.

The Exon view, available from the Gene perspective, gives the precise coordinates of all protein isoforms that can be mapped on Ensembl transcripts, based on exons. For each exon, its position on the gene is shown, as well as the length if the exon in nucleotides. The coding regions are represented by a small glyph, in which coding fragments are shown with a large green line, and non-coding sequences by a thin gray line. (Strictly non-coding exons are not shown.) The first and the last amino acid of each exon are shown, and the reading frame of each exon is indicated by red labeling of the amino acids. For example, Val 96–Ile 110 means that the first amino acid of that exon (Val) is completely encoded within that exon, while only the first nucleotide of the last one (Ile) is encoded in that exon.

Figure 6.

For each term within the ontologies and hierarchical controlled vocabularies, a dedicated page shows its definition, synonyms and cross-references to other ontologies. In addition, the Graphical Ontology Viewer shows the relationship of that term to all its parents.