Thursday, October 8, 2020

Introducing the UniProt Alzheimer’s disease portal

INTRODUCTION

Alzheimer's disease (AD), the most common subtype of dementia, is the most prevalent neurodegenerative disorder with an estimated 30-35 million living with the disease worldwide. It is characterized by progressive memory loss, cognitive decline, and eventually leads to the loss of bodily functions and ultimately death.  

Although much is known about this complex disease, the underlying cause remains unclear. Current research suggests that the risk of developing AD is influenced by both genetic and environmental factors as well as age; although it is not a normal part of ageing. 

Despite considerable global scientific efforts into developing drugs, vaccines and other medical treatments, there are currently no effective medications for the prevention and treatment of AD. Since 1998, 146 drugs have been tested and rejected, and the four drugs that have been approved for therapeutic use only have modest symptom-reducing effects and do not alter the eventual progression of AD. 

It is therefore critical that the plethora of data generated by this research is collected, organized, freely-available and accessible to researchers, in order to increase the pace of discovery and innovation.

UniProt

To better serve the needs of the AD research community and to facilitate discoverability, UniProt has developed the Alzheimer’s disease portal to help researchers explore and access current AD genomic-based data from the UniProtKB database, but in a single centralized UniProt disease portal.  It is linked from the UniProt Alzheimer Disease page in the first beta release.



Developed with the help of AD researchers, the portal incorporates UniProt functional annotations, protein network visualizations, and has integrated genomic and drug-related data from other resources; allowing users to easily visualize and compare data to identify similarities using variants, protein interactions, diseases, and drug data. The portal follows a card-based approach to allow exploration of interconnected data. For example, the navigation connects you from a given Disease to an associated protein to another disease that the protein may be involved in.


The landing page shows a disease card with a disease description and a dropdown to select sub-types for the disease. Further, it presents three tabs with associated proteins, drug candidates and UniProt curated sequence variants.

The ‘Proteins’ tab allows quick filtering and download of the entire protein dataset. For each protein, you can view all its interactions, all pathways it is involved in, all sequence variants it is known to have (including UniProt curated variants as well predicted variants from Large Scale Studies), all diseases that the protein is associated with according to UniProt curation, and any drugs linked to the disease according to Chembl. 

The Drug candidates tab shows all drug candidates associated with the disease from Chembl and Open Targets, with the max phase, mechanism of action, links to Chembl, links to literature, associated diseases and associated UniProt proteins for each drug.

The Sequence variants tab presents all UniProt curated sequence variants associated with the disease.



Try out the UniProt Disease Portal and help us develop it further for your requirements by sending us feedback through the ‘Feedback’ link in the header.



References

Cummings J, Lee G, Ritter A, Sabbagh M, Zhong K. Alzheimer's disease drug development pipeline: 2020. Alzheimers Dement. (2020);6(1):e12050. DOI: 10.1002/trc2.12050. UniProt Consortium. A Coordinated Approach by Public Domain Bioinformatics Resources to Aid the Fight Against Alzheimer's Disease Through Expert Curation of Key Protein Targets. J Alzheimers Dis. (2020);77(1):257-273. DOI: 10.3233/JAD-200206  

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