Phen-Gen: Combining Phenotype and Genotype to Analyze Rare Disorders

Abstract

We introduce Phen-Gen, a method which combines patients disease symptoms and sequencing data with prior domain knowledge to identify the causative gene(s) for rare disorders. Simulations reveal that the causal variant is ranked first in 88% cases when it is coding; which is 52% advantage over a genotype-only approach and outperforms existing methods by 13-58%. If disease etiology is unknown, the causal variant is assigned top-rank in 71% of simulations.