Protein Language Models traditionally depend on Multiple Sequence Alignments (MSA) to incorporate evolutionary knowledge. However, MSA-based approaches suffer from substantial computational overhead and generally underperform in generalizing to de novo proteins. This study reevaluates the role of MSA, proposing it as a retrieval augmentation method and questioning the necessity of sequence alignment. We show that a simple alternative, Retrieved Sequence Augmentation (RSA), can enhance protein representation learning without the need for alignment and cumbersome preprocessing. RSA surpasses MSA Transformer by an average of 5% in both structural and property prediction tasks while being 373 times faster. Additionally, RSA demonstrates enhanced transferability for predicting de novo proteins. This methodology addresses a critical need for efficiency in protein prediction and can be rapidly employed to identify homologous sequences, improve representation learning, and enhance the capacity of Large Language Models to interpret protein structures.

With promising yet saturated results in high-resource settings, low-resource datasets have gradually become crucial benchmarks (e.g., BigBench Hard, superGLUE) for evaluating the learning ability of advanced neural networks. In this work, we find that there exists a set of “hard examples” in low-resource settings that challenge neural networks but are not well evaluated, which causes over-estimated performance. We first give a theoretical analysis on which factors bring the difficulty of low-resource learning. It then motivates us to propose a challenging benchmark Achilles-Bench to better evaluate the learning ability, which covers 11 datasets, including 8 natural language process (NLP) datasets and 3 computer vision (CV) datasets. Experiments on a wide range of models show that neural networks, even pre-trained language models, have sharp performance drops on our benchmark, demonstrating the effectiveness of evaluating the weaknesses of neural networks. On NLP tasks, we surprisingly find that despite better results on traditional low-resource benchmarks, pre-trained networks, does not show performance improvements on our benchmarks. there is still a large robustness gap between existing models and human-level performance, highlighting the need for robust low-resource learning models.