Prioritization and functional assessment of noncoding variants associated with complex diseases

Genome Med. 2018 Jul 11;10(1):53. doi: 10.1186/s13073-018-0565-y.


Unraveling functional noncoding variants associated with complex diseases is still a great challenge. We present a novel algorithm, Prioritization And Functional Assessment (PAFA), that prioritizes and assesses the functionality of genetic variants by introducing population differentiation measures and recalibrating training variants. Comprehensive evaluations demonstrate that PAFA exhibits much higher sensitivity and specificity in prioritizing noncoding risk variants than existing methods. PAFA achieves improved performance in distinguishing both common and rare recurrent variants from non-recurrent variants by integrating multiple annotations and metrics. An integrated platform was developed, providing comprehensive functional annotations for noncoding variants by integrating functional genomic data, which can be accessed at .

Keywords: Complex disease; Functional annotation; Genetic variant; Noncoding variant; Variant prioritization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • DNA, Intergenic / genetics*
  • Disease / genetics*
  • Genetic Variation*
  • Humans
  • Neoplasms / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors


  • DNA, Intergenic