Diagnosing protein sequence search in the era of language models (opens in new tab)

Protein language model (PLM) based search is rapidly emerging as a successor to classical sequence alignment, with recent high-profile studies reporting substantial improvements in speed and remote homology detection. However, success on standard benchmarks does not guarantee that similarity derived from PLM embeddings constitutes reliable biological evidence. Here, we introduce PLM-GUARD, a diagnostic framework designed to interrogate the underlying meaning of protein search scores and asses...