A domain damage index to prioritizing the pathogenicity of missense variants

Hua Chang Chen, Jing Wang, Qi Liu, Yu Shyr

研究成果: Article同行評審


Prioritizing causal variants is one major challenge for the clinical application of sequencing data. Prompted by the observation that 74.3% of missense pathogenic variants locate in protein domains, we developed an approach named domain damage index (DDI). DDI identifies protein domains depleted of rare missense variations in the general population, which can be further used as a metric to prioritize variants. DDI is significantly correlated with phylogenetic conservation, variant-level metrics, and reported pathogenicity. DDI achieved great performance for distinguishing pathogenic variants from benign ones in three benchmark datasets. The combination of DDI with the other two best approaches improved the performance of each individual method considerably, suggesting DDI provides a powerful and complementary way of variant prioritization.

頁(從 - 到)1503-1517
期刊Human mutation
出版狀態Published - 2021 11月

All Science Journal Classification (ASJC) codes

  • 遺傳學
  • 遺傳學(臨床)


深入研究「A domain damage index to prioritizing the pathogenicity of missense variants」主題。共同形成了獨特的指紋。