EXPERT PROGRAM AUTOMATES IDENTIFICATION OF HUMAN DISEASE CAUSING MUTATIONS LEVERAGING LARGE PATIENT DATA SETS

摘要

Next-Generation Sequencing (NGS) based genetic diagnosis has immense potential to improve medical practice. Two major remaining obstacles to the widespread clinical use of NGS are the cost of supporting a team of geneticists and concerns over reproducibility of results. To address these concerns, a computer-based method and system is presented that automates the process of performing a genetic diagnosis by leveraging sequencing and phenotype data mined from thousands of patients. The resulting EXPERT system lists the probability that every mutant gene causes disease. Taking the highest scoring gene generates a genetic diagnosis identical to that of human experts 90% of the time, with differences occurring largely in unclear cases. In addition, the probability assigned to a gene by the EXPERT system is closely correlated with the subjective "confidence" of a prediction assigned by human experts examining the same patient. This system thus automates the genetic diagnosis process, and has the potential to allow for fast, simple, and reliable genetic diagnosis.