Protein language models (PLMs) are often assumed to capture evolutionary information by training on large protein sequence datasets. Yet it remains unclear whether PLMs can reason about evolution--that is, infer evolutionary relationships between sequences. We test this capability by evaluating whether standard PLM usage, frozen or fine-tuned embeddings with distance-based comparison, supports evolutionary reasoning. Existing PLMs consistently fail to recover phylogenetic structure, despite strong performance on sequence-level tasks such as masked-token and contact prediction. We present Phyla, a hybrid state-space and transformer model that jointly processes multiple sequences and is trained using a tree-based objective across 3,000 phylogenies spanning diverse protein families.

Generative protein language models (PLMs) are powerful tools for designing proteins purpose-built to solve problems in medicine, agriculture, and industrial processes. Recent work has trained ever larger language models, but there has been little systematic study of the optimal training distributions and the influence of model scale on the sequences generated by PLMs. We introduce the ProGen3 family of sparse generative PLMs, and we develop compute-optimal scaling laws to scale up to a 46B-parameter model pre-trained on 1.5T amino acid tokens. ProGen3's pre-training data is sampled from an optimized data distribution over the PPA v1, a carefully curated dataset of 3.4B full-length proteins. We evaluate for the first time in the wet lab the influence of model scale on the sequences generated by PLMs, and we find that larger models generate viable proteins for a much wider diversity of protein families. Finally, we find both computationally and experimentally that larger models are more responsive to alignment with laboratory data, resulting in improved protein fitness prediction and sequence generation capabilities. These results indicate that larger PLMs like ProGen3-46B trained on larger, well-curated datasets are powerful foundation models that push the frontier of protein design.

The accurate identification of active sites in proteins is essential for the advancement of life sciences and pharmaceutical development, as these sites are of critical importance for enzyme activity and drug design. Recent advancements in protein language models (PLMs), trained on extensive datasets of amino acid sequences, have significantly improved our understanding of proteins. However, compared to the abundant protein sequence data, functional annotations, especially precise per-residue annotations, are scarce, which limits the performance of PLMs. On the other hand, textual descriptions of proteins, which could be annotated by human experts or a pretrained protein sequence-to-text model, provide meaningful context that could assist in the functional annotations, such as the localization of active sites. This motivates us to construct a $\textbf{ProT}$ein-$\textbf{A}$ttribute text $\textbf{D}$ataset ($\textbf{ProTAD}$), comprising over 570,000 pairs of protein sequences and multi-attribute textual descriptions.

Recent advances in prompt optimization have notably enhanced the performance of pre-trained language models (PLMs) on downstream tasks. However, the potential of optimized prompts on domain generalization has been under-explored. To explore the nature of prompt generalization on unknown domains, we conduct pilot experiments and find that (i) Prompts gaining more attention weight from PLMs' deep layers are more generalizable and (ii) Prompts with more stable attention distributions in PLMs' deep layers are more generalizable. Thus, we offer a fresh objective towards domain-generalizable prompts optimization named ''Concentration'', which represents the ''lookback'' attention from the current decoding token to the prompt tokens, to increase the attention strength on prompts and reduce the fluctuation of attention distribution.We adapt this new objective to popular soft prompt and hard prompt optimization methods, respectively. Extensive experiments demonstrate that our idea improves comparison prompt optimization methods by 1.42% for soft prompt generalization and 2.16% for hard prompt generalization in accuracy on the multi-source domain generalization setting, while maintaining satisfying in-domain performance. The promising results validate the effectiveness of our proposed prompt optimization objective and provide key insights into domain-generalizable prompts.

In the field of natural language processing, the prevalent approach involves fine-tuning pretrained language models (PLMs) using local samples.

Accurately modeling weather variation pattern from large amount of meteorological variables sequences is increasingly vital for providing efficient weather analysis support for disaster warning.