Genetic variations and diseases in UniProtKB/Swiss-Prot: The ins and outs of expert manual curation

By M. Famiglietti, A. Estreicher, A. Gos, Jerven T. Bolleman, S. Gehant, L. Breuza, A. Bridge, S. Poux, Nicole Redaschi, L. Bougueleret and 1 more. 2014

50 citations recorded by the source corpus.

During the last few years, next‐generation sequencing (NGS) technologies have accelerated the detection of genetic variants resulting in the rapid discovery of new disease‐associated genes. However, the wealth of variation data made available by NGS alone is not sufficient to understand the mechanisms underlying disease pathogenesis and manifestation. Multidisciplinary approaches combining sequence and clinical data with prior biological knowledge are needed to unravel the role of genetic variants in human health and disease. In this context, it is crucial that these data are linked, organized, and made readily available through reliable online resources. The Swiss‐Prot section of the Universal Protein Knowledgebase (UniProtKB/Swiss‐Prot) provides the scientific community with a collection of information on protein functions, interactions, biological pathways, as well as human genetic diseases and variants, all manually reviewed by experts. In this article, we present an overview of the information content of UniProtKB/Swiss‐Prot to show how this knowledgebase can support researchers in the elucidation of the mechanisms leading from a molecular defect to a disease phenotype.

Subfields: Genetics, Molecular Biology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

In Molecular Biology

Citations in the corpus

UniProt: the universal protein knowledgebase (2016, background): “UniProtKB contains decades of literature-based and semi-automated curation describing protein function including variation data (28).”
The UniProtKB guide to the human proteome (2016, background): “The disease is described in a structured format based on OMIM disease nomenclature, if available, and contains cross-references to the OMIM database and MeSH terms [detailed information about human variations and diseases in UniProtKB/ Swiss-Prot is described in (25)].”
The SIB Swiss Institute of Bioinformatics’ resources: focus on curated databases (2015, background): “org) provides comprehensive expert-curated functional annotation for over 540 000 protein sequences, including descriptions of protein function, location, interactions and domain structure, as well as post-translational modifications (PTMs) and variants and their functional impact (18).”
The Transporter Classification Database (TCDB): recent advances (2015, methodology): “GENEW (28) Almost all human transporters can now be found in TCDB and are annotated using the Human Gene Nomenclature DB system UniProt Disease (29) Users can identify diseases associated with any transporter class, (super)family, or system PFAM (30) Transport systems are cross-referenced with PFAM ”
MalaCards: an amalgamated human disease compendium with diverse clinical and genetic annotation and structured search (2016, background): “Given the importance of gene-disease associations, much research attention has been directed to improved algorithms for generating such connections (5,20,30,31).”
Recon3D: A Resource Enabling A Three-Dimensional View of Gene Variation in Human Metabolism (2018, unknown): “We analyzed SNP data from multiple gene variation databases (dbSNP 30 , UniProt 24 , PharmGKB 31 ) and assessed whether the 3D location of variants in a gene could, in general, discern whether mutations were deleterious or tolerated 41 .”