dbNSFP v4: a comprehensive database of transcript-specific functional predictions and annotations for human...

Area of Science:

• Genomics
• Bioinformatics
• Human Genetics

Background:

• Whole exome sequencing (WES) is crucial for identifying genetic variants in human diseases.
• Effective variant prioritization using functional annotations is essential for disease gene discovery.
• Existing databases require updates to encompass the growing volume of genetic data and prediction tools.

Purpose of the Study:

• To present the latest updates to the dbNSFP database (version 4.1).
• To provide comprehensive deleteriousness predictions and functional annotations for human genetic variants.
• To facilitate the selection of candidate variants in human disease studies.

Main Methods:

• Compilation of 36 deleteriousness prediction scores, including 12 transcript-specific scores.
• Inclusion of variant and gene-level functional annotations.
• Database development for all potential nonsynonymous and splice-site single nucleotide variants (SNVs).

Main Results:

• dbNSFP version 4.1 now includes annotations for 84,013,093 potential nonsynonymous and splice-site SNVs.
• The database integrates a wide array of prediction scores and functional annotations.
• A publicly accessible web service and downloadable version are provided.

Conclusions:

• dbNSFP 4.1 serves as a vital resource for researchers utilizing whole exome sequencing data.
• The updated database significantly aids in the functional interpretation and prioritization of genetic variants.
• Enhanced annotation capabilities improve the efficiency of identifying disease-causing mutations.