The George
Sometimes, in genetics, two wrongs do make a right. A research team recently showed that two harmful genetic variants, when occurring together in a gene, can restore function—proving a decades-old hypothesis originally proposed by Nobel laureate Francis Crick. Their study, published in the Proceedings of the National Academy of Sciences (PNAS), not only experimentally validated this theory but also introduced a powerful artificial intelligence (AI)-driven approach to genetic interpretation led by George Mason University researchers.
The project began when Aimée Dudley, a geneticist at the Pacific Northwest Research Institute (PNRI), approached George Mason University Chief AI Officer Amarda Shehu after following her lab’s work on frontier AI models for predicting the functional impact of genetic variation. That conversation sparked a collaboration that married PNRI’s experimental expertise with George Mason’s computational innovation to discover some surprising ways variant combinations can shape human health.
The problem
Every year one in three Americans is diagnosed with a genetic disorder. Symptoms manifest in infancy for about 70% of individuals. Sadly, 35% die before the age of 5. Advancements in clinical genomics offer hope to better understand and possibly treat these disorders.
“High-throughput genomic screening has been a wonderful feat for humanity,” said Shehu, “but one of its side effects is that it has produced massive amounts of data, outpacing our ability to interpret what that data means for health and disease.”
Research in the Shehu lab has for years focused on building frontier AI models to advance genetic interpretation, but all data available link only isolated, single variants to measured functional activity. Because each person’s genome contains billions of base pairs, with about five million variants existing between two individuals’ genomes, looking at one variant at a time rather than combinations of variants could only reveal so much.
“It looked like we had hit a wall,” Shehu said, “that is, until Dr. Dudley contacted my lab more than a year ago.”
