How can we better understand pathogenic variants in intrinsically disordered regions (IDRs)? How do models such as AlphaMissense and ESM1b predict pathogenicity, when these regions typically exhibit lower genomic conservation than ordered regions? Read more: doi.org/10.1101/2025...

Protein language model likelihood are better zero shot mutation effect predictions when they have perplexity 3-6 on the wildtype sequence. www.biorxiv.org/content/10.1...

Why do large protein language models like ESM2-15B underperform compared to medium-sized ones like ESM2-650M in predicting mutation effects? 🤔 We dive into this issue in our new preprint—bringing insights into model scaling on mutation effect prediction. 🧬📉