PRBB Computational Genomics Seminars

25/09/202512:00R_473.10_AULAPRBB Computational Genomics SeminarsCharles PughProbabilistic machine learning and genomics group (Dias & Frazer Lab). CRG"From Likelihood to Fitness: Improving Variant Effect Prediction in Protein and Genome Language Models"Abstract:Generative models trained on natural sequences are increasingly used to predict the effects of genetic variation, enabling progress in therapeutic design, disease risk prediction, and synthetic biology. In the zero-shot setting, variant impact is estimated by comparing the likelihoods of sequences, under the assumption that likelihood serves as a proxy for fitness. However, this assumption often breaks down in practice: sequence likelihood reflects not only evolutionary fitness constraints, but also...