MOTIVATION: Accurately identifying compound-protein interactions (CPIs) is critical for accelerating drug discovery. Recent deep learning methods have achieved impressive results, yet they primarily focus on local structures and neighborhood information, often overlooking high-order interaction patterns shared among similar molecules. RESULTS: In this paper, we propose HKD-CPI, a high-order knowledge-enhanced inductive framework designed to improve generalization to unseen compound-protein pairs. Specifically, HKD-CPI introduces a molecular graph tokenization mechanism that aligns compound molecular graph features with token embeddings from sequence-pretrained large language models (LLMs), effectively infusing sequence-derived semantics into structural representations. To capture shared interaction patterns among functionally similar biomolecules, we construct a hypergraph-based representation to model high-order relationships between feature-similar compound/protein groups and their binding partners. Furthermore, a knowledge distillation strategy is further adopted to transfer high-order interaction knowledge from the hypergraph to a lightweight student model, enabling efficient and robust CPI prediction. Extensive experiments demonstrate that HKD-CPI outperforms existing state-of-the-art methods in inductive CPI prediction tasks. In particular, it achieves an average improvement of 4.94% in AUROC and 3.64% in AUPRC over the best-performing baseline across five benchmark datasets. AVAILABILITY AND IMPLEMENTATION: Our code and data are available at https://github.com/Hezy618/HKD-CPI.

MOTIVATION: The interaction between peptides and human leukocyte antigen class II (HLA-II) molecules plays a pivotal role in adaptive immune responses, as HLA-II mediates the recognition of exogenous antigens and initiates T cell activation through peptide presentation. Accurate prediction of peptide-HLA-II binding serves as a cornerstone for deciphering cellular immune responses, and is essential for guiding the optimization of antibody therapeutics. Researchers have developed several computational approaches to identify peptide-HLA-II interaction and presentation. However, most computational approaches exhibit inconsistent predictive performance, poor generalization ability and limited biological interpretability. RESULTS: In this study, we present DSCA-HLAII, a novel predictive framework for peptide-HLA-II interactions and presentation based on a dual-stream cross-attention architecture. The framework proposes a dual-stream cross-attention (DSCA) mechanism to integrate pre-trained semantic embedding ESMC with sequence-level ONE-HOT features. The DSCA mechanism effectively models the interaction dynamics between peptides and HLA-II molecules, enabling the precise identification of key binding sites. Experimental results demonstrate that DSCA-HLAII consistently surpasses existing state-of-the-art approaches, demonstrating high accuracy and robustness in predicting peptide-HLA-II interactions and presentation. We further demonstrate the capability of DSCA-HLAII for predicting peptide binding cores and assessing antibody immunogenicity, which is expected to advance artificial intelligence-based peptide drug discovery.

Malware is software designed to infiltrate or damage a computer system without the owner's informed consent (e.g., viruses, backdoors, spyware, trojans, and worms). Nowadays, numerous attacks made by the malware pose a major security threat to computer users. Unfortunately, along with the development of the malware writing techniques, the number of file samples that need to be analyzed, named "gray list," on a daily basis is constantly increasing. In order to help our virus analysts, quickly and efficiently pick out the malicious executables from the "gray list," an automatic and robust tool to analyze and classify the file samples is needed. In our previous work, we have developed an intelligent malware detection system (IMDS) by adopting associative classification method based on the analysis of application programming interface (API) execution calls. Despite its good performance in malware detection, IMDS still faces the following two challenges: (1) handling the large set of the generated rules to build the classifier; and (2) finding effective rules for classifying new file samples. In this paper, we first systematically evaluate the effects of the postprocessing techniques (e.g., rule pruning, rule ranking, and rule selection) of associative classification in malware detection, and then, propose an effective way, i.e., CIDCPF, to detect the malware from the "gray list." To the best of our knowledge, this is the first effort on using postprocessing techniques of associative classification in malware detection. CIDCPF adapts the postprocessing techniques as follows: first applying Chi-square testing and Insignificant rule pruning followed by using Database coverage based on the Chi-square measure rule ranking mechanism and Pessimistic error estimation, and finally performing prediction by selecting the best First rule. We have incorporated the CIDCPF method into our existing IMDS system, and we call the new system as CIMDS system. Case studies are performed on the large collection of file samples obtained from the Antivirus Laboratory at Kingsoft Corporation and promising experimental results demonstrate that the efficiency and ability of detecting malware from the "gray list" of our CIMDS system outperform popular antivirus software tools, such as McAfee VirusScan and Norton Antivirus, as well as previous data-mining-based detection systems, which employed Naive Bayes, support vector machine, and decision tree techniques. In particular, our CIMDS system can greatly reduce the number of generated rules, which makes it easy for our virus analysts to identify the useful ones.