Testing the mutation accumulation hypothesis in aging with AlphaGenome (opens in new tab)

The mutation accumulation (MA) hypothesis posits that somatic mutations progressively escape selection and degrade tissue function during aging. Direct tests of this idea have been limited by the difficulty of predicting, at scale, the molecular consequences of individual somatic variants. Here I use AlphaGenome, a sequence-to-function deep learning model, to systematically score the predicted transcriptional impact of somatic mutations under a nested series of designs spanning individual var...