Ruochi Zhang

Kewei Li, Yuqian Wu, Yinheng Li et al.

Since the mechanism of action of drug molecules in the human body is difficult to reproduce in the in vitro environment, it becomes difficult to reveal the causes of the activity cliff phenomenon of drug molecules. We found out the AC of small molecules has been extensively investigated but limited knowledge is accumulated about the AC phenomenon in peptides with canonical amino acids. Understanding the mechanism of AC in canonical amino acids might help understand the one in drug molecules. This study introduces a quantitative definition and benchmarking framework AMPCliff for the AC phenomenon in antimicrobial peptides (AMPs) composed by canonical amino acids. A comprehensive analysis of the existing AMP dataset reveals a significant prevalence of AC within AMPs. AMPCliff quantifies the activities of AMPs by the MIC, and defines 0.9 as the minimum threshold for the normalized BLOSUM62 similarity score between a pair of aligned peptides with at least two-fold MIC changes. This study establishes a benchmark dataset of paired AMPs in Staphylococcus aureus from the publicly available AMP dataset GRAMPA, and conducts a rigorous procedure to evaluate various AMP AC prediction models, including nine machine learning, four deep learning algorithms, four masked language models, and four generative language models. Our analysis reveals that these models are capable of detecting AMP AC events and the pre-trained protein language model ESM2 demonstrates superior performance across the evaluations. The predictive performance of AMP activity cliffs remains to be further improved, considering that ESM2 with 33 layers only achieves the Spearman correlation coefficient 0.4669 for the regression task of the MIC values on the benchmark dataset. Source code and additional resources are available at https://www.healthinformaticslab.org/supp/ or https://github.com/Kewei2023/AMPCliff-generation.

Kewei Li, Yanwen Kong, Yiping Xu et al.

Since the emergence of research on improving the length extrapolation capabilities of large language models in 2021, some studies have made modifications to the scaling factor in the scaled dot-product attention mechanism as part of their proposed methods without rigorous theoretical justifications. To fill this gap, we propose two new scaled temperatures based on information entropy invariance to enhance length extrapolation. First, a training-free method InfoScale is designed for dotproduct attention, and preserves focus on original tokens during length extrapolation by ensuring consistent entropy. Second, we theoretically analyze the impact of scaling (CosScale) on cosine attention. Experimental data demonstrates that combining InfoScale and CosScale achieves state-ofthe-art performance on the GAU-α model with a context window extended to 64 times the training length, and outperforms seven existing methods. Our analysis reveals that significantly increasing CosScale approximates the Windowed Attention, and highlights the significance of attention score dilution as a key challenge in long-range context handling. The code and data are available at https://github.com/HT-NEKO/ Information-Entropy-Invariance.

Jiale Zhang, Pengfei He, Fei Li et al.

In today's fast-paced digital communication, the surge in network traffic data and frequency demands robust and precise network intrusion solutions. Conventional machine learning methods struggle to grapple with complex patterns within the vast network intrusion datasets, which suffer from data scarcity and class imbalance. As a result, we have integrated machine learning and deep learning techniques within the network intrusion detection system to bridge this gap. This study has developed TrailGate, a novel framework that combines machine learning and deep learning techniques. By integrating Transformer and Bidirectional Gated Recurrent Unit (BiGRU) architectures with advanced feature selection strategies and supplemented by data augmentation techniques, TrailGate can identifies common attack types and excels at detecting and mitigating emerging threats. This algorithmic fusion excels at detecting common and well-understood attack types and has the unique ability to swiftly identify and neutralize emerging threats that stem from existing paradigms.