ActiveDriverDB 2021

Released 16 December 2020

PTM sites

• Sites were updated using the latest UniProt and PhosphoSitePlus versions
• SARS-CoV-2 associated phosphorylation sites from (Bouhaddou et al., 2020) were added
• Outdated PTMvar sites are no longer included
• Sumoylation and succinylation sites were added

Mutations

• ClinVar mutations were updated to October 2020 release (2020-10-03)
  • by default only pathogenic, likely pathogenic, and likely pathogenic/pathogenic mutations are displayed, but this restriction can be changed to include other levels of clinical significance by adjusting data filters
  • filtering by the number of gold stars, which signify review status, is now possible; this filter is optional and disabled by default
• PCAWG cancer mutations were added

Sequence view

• The box displayed when hovering over sites now includes phosphorylation change association if present (e.g. increase or decrease in phosphorylation upon SARS-CoV-2 infection)
• Details in the mutation table now correctly display the PTM site type

Network view

• The box displayed when hovering over drug nodes includes the action of the drug (e.g. inhibitor/antagonist/agonist)
• Full-screen mode was added to allow for easier inspection of crowded networks

Data updates tables 

The release date denotes the date of release by the data source maintainers if know, or otherwise the date the data was downloaded and incorporated into the ActiveDriverDB.

*) or download date for sources with no dated releases

ActiveDriverDB 2020

Released 15 March 2020

PTM sites

• Glycosylation sites (N-, O-, S-, C-) were added based on the UniProt (May 2019)
• Other types of PTM sites were updated using the UniProt data
• The origin database is now stored and displayed for each PTM site to help users in further investigation, including scrutinizing the evidence quality and citing the original reporters. It can be accessed by hovering over the site in the sequence view:
  
• The code for mapping sites across isoforms has been improved and included in the released source code

Mutations

Inherited mutations with clinical significance (from ClinVar)

• Clinical mutations from ClinVar were updated using May 2019 release (20190520)

• ClinVar mutations are now stringently filtered to only include clinically relevant, non-somatic mutations. Specifically:

  • mutations with germline, parental, maternal, biparental, etc origin are included; de novo mutations are also included,
  • mutations with a somatic origin, or missing the origin information are excluded (see here for the exclusion list),
  • only mutations associated with a disease, or conferring sensitivity (but not resistance) are included (details here)

• ClinVar mutations include more metadata:

  • gold stars which describe the quality of evidence are now displayed (one per underlying variation),
  • links to both the dbSNP entry (e.g. ncbi.nlm.nih.gov/snp/rs755131800) and the variation entries in ClinVar database (VCV record, e.g. ncbi.nlm.nih.gov/clinvar/variation/548576/) are now provided
    

Genes

Gene information (including identifiers mapping to external databases) were updated using the UCSC Genome Browser distributed tables of RefSeq database and the UniProt database.

Sequence view

• conservation track showing phyloP scores (based on the 100way track from UCSC Genome Browser) was added. The per-aminoacid scores were calculated as an average of the codon scores.

Active genes

• ActiveDriver results for ClinVar are now computed on the pathogenic/likely pathogenic/drug response subset of mutations

Pathways

• Reactome and Gene Ontology pathways were updated (8th March 2020)
• Top pathways were calculated using ActivePathways

Technical aspects

• BerkeleyDB was replaced with LightningDB offering higher performance for bulk mutations queries
• The filtering system was updated; If yous saved old URLs including filters, you can still use it with v2017, but new URLs require adjustments.

Data updates tables