Guangyu Wang

Rong Han, Xiaohong Liu, Tong Pan et al.

Accurately measuring protein-RNA binding affinity is crucial in many biological processes and drug design. Previous computational methods for protein-RNA binding affinity prediction rely on either sequence or structure features, unable to capture the binding mechanisms comprehensively. The recent emerging pre-trained language models trained on massive unsupervised sequences of protein and RNA have shown strong representation ability for various in-domain downstream tasks, including binding site prediction. However, applying different-domain language models collaboratively for complex-level tasks remains unexplored. In this paper, we propose CoPRA to bridge pre-trained language models from different biological domains via Complex structure for Protein-RNA binding Affinity prediction. We demonstrate for the first time that cross-biological modal language models can collaborate to improve binding affinity prediction. We propose a Co-Former to combine the cross-modal sequence and structure information and a bi-scope pre-training strategy for improving Co-Former's interaction understanding. Meanwhile, we build the largest protein-RNA binding affinity dataset PRA310 for performance evaluation. We also test our model on a public dataset for mutation effect prediction. CoPRA reaches state-of-the-art performance on all the datasets. We provide extensive analyses and verify that CoPRA can (1) accurately predict the protein-RNA binding affinity; (2) understand the binding affinity change caused by mutations; and (3) benefit from scaling data and model size.

Huan Ma, Jingdong Chen, Joey Tianyi Zhou et al.

Over the past few years, Large Language Models (LLMs) have developed rapidly and are widely applied in various domains. However, LLMs face the issue of hallucinations, generating responses that may be unreliable when the models lack relevant knowledge. To be aware of potential hallucinations, uncertainty estimation methods have been introduced, and most of them have confirmed that reliability lies in critical tokens. However, probability-based methods perform poorly in identifying token reliability, limiting their practical utility. In this paper, we reveal that the probability-based method fails to estimate token reliability due to the loss of evidence strength information which is accumulated in the training stage. Therefore, we present Logits-induced token uncertainty (LogTokU), a framework for estimating decoupled token uncertainty in LLMs, enabling real-time uncertainty estimation without requiring multiple sampling processes. We employ evidence modeling to implement LogTokU and use the estimated uncertainty to guide downstream tasks. The experimental results demonstrate that LogTokU has significant effectiveness and promise.