Mike’s papers on the spatial distribution of genetic variants in protein 3D structures are published!

Congratulations to recently graduated PhD student Mike Sively on publication of two papers describing his work on the spatial distribution of human genetic variation in protein 3D structures and models. The first, published in the American Journal of Human Genetics, describes a comprehensive analysis of more the four million genetic variants in their structural contexts. We found that pathogenic and benign variants exhibit different patterns of spatial constraint, and that these patterns can be informative about protein function:
Comprehensive Analysis of Constraint on the Spatial Distribution of Missense Variants in Human Protein Structures

The second paper describes an application of the analysis of the spatial distribution of pathogenic and benign variants to characterized uncharacterized variants in RTEL1 identified in patients with pulmonary fibrosis. Our new PathProx performs competitively with popular methods for pathogenicity prediction and suggests specific hypotheses for how variants influence protein function:
Three-dimensional spatial analysis of missense variants in RTEL1 identifies pathogenic variants in patients with Familial Interstitial Pneumonia