Shengjie Xu

Gary A. McCully, John D. Hastings, Shengjie Xu et al.

Ransomware and other forms of malware cause significant financial and operational damage to organizations by exploiting long-standing and often difficult-to-detect software vulnerabilities. To detect vulnerabilities such as buffer overflows in compiled code, this research investigates the application of unidirectional transformer-based embeddings, specifically GPT-2. Using a dataset of LLVM functions, we trained a GPT-2 model to generate embeddings, which were subsequently used to build LSTM neural networks to differentiate between vulnerable and non-vulnerable code. Our study reveals that embeddings from the GPT-2 model significantly outperform those from bidirectional models of BERT and RoBERTa, achieving an accuracy of 92.5% and an F1-score of 89.7%. LSTM neural networks were developed with both frozen and unfrozen embedding model layers. The model with the highest performance was achieved when the embedding layers were unfrozen. Further, the research finds that, in exploring the impact of different optimizers within this domain, the SGD optimizer demonstrates superior performance over Adam. Overall, these findings reveal important insights into the potential of unidirectional transformer-based approaches in enhancing cybersecurity defenses.

Shengjie Xu, Xianbin Ye, Mengran Zhu et al.

Identifying protein targets for small molecules, or reverse screening, is essential for understanding drug action, guiding compound repurposing, predicting off-target effects, and elucidating the molecular mechanisms of bioactive compounds. Despite its critical role, reverse screening remains challenging because accurately capturing interactions between a small molecule and structurally diverse proteins is inherently complex, and conventional step-wise workflows often propagate errors across decoupled steps such as target structure modeling, pocket identification, docking, and scoring. Here, we present an end-to-end reverse screening strategy leveraging HelixFold3, a high-accuracy biomolecular structure prediction model akin to AlphaFold3, which simultaneously models the folding of proteins from a protein library and the docking of small-molecule ligands within a unified framework. We validate this approach on a diverse and representative set of approximately one hundred small molecules. Compared with conventional reverse docking, our method improves screening accuracy and demonstrates enhanced structural fidelity, binding-site precision, and target prioritization. By systematically linking small molecules to their protein targets, this framework establishes a scalable and straightforward platform for dissecting molecular mechanisms, exploring off-target interactions, and supporting rational drug discovery.

Shengjie Xu, Lingxi Xie

Antibody-drug conjugates (ADCs) have emerged as a promising class of targeted cancer therapeutics, but the design and optimization of their cytotoxic payloads remain challenging. This study introduces DumplingGNN, a novel hybrid Graph Neural Network architecture specifically designed for predicting ADC payload activity based on chemical structure. By integrating Message Passing Neural Networks (MPNN), Graph Attention Networks (GAT), and GraphSAGE layers, DumplingGNN effectively captures multi-scale molecular features and leverages both 2D topological and 3D structural information. We evaluate DumplingGNN on a comprehensive ADC payload dataset focusing on DNA Topoisomerase I inhibitors, as well as on multiple public benchmarks from MoleculeNet. DumplingGNN achieves state-of-the-art performance across several datasets, including BBBP (96.4\% ROC-AUC), ToxCast (78.2\% ROC-AUC), and PCBA (88.87\% ROC-AUC). On our specialized ADC payload dataset, it demonstrates exceptional accuracy (91.48\%), sensitivity (95.08\%), and specificity (97.54\%). Ablation studies confirm the synergistic effects of the hybrid architecture and the critical role of 3D structural information in enhancing predictive accuracy. The model's strong interpretability, enabled by attention mechanisms, provides valuable insights into structure-activity relationships. DumplingGNN represents a significant advancement in molecular property prediction, with particular promise for accelerating the design and optimization of ADC payloads in targeted cancer therapy development.

Gary A. McCully, John D. Hastings, Shengjie Xu

This study examines the impact of data snooping on neural networks used to detect vulnerabilities in lifted code, and builds on previous research that used word2vec and unidirectional and bidirectional transformer-based embeddings. The research specifically focuses on how model performance is affected when embedding models are trained with datasets, which include samples used for neural network training and validation. The results show that introducing data snooping did not significantly alter model performance, suggesting that data snooping had a minimal impact or that samples randomly dropped as part of the methodology contained hidden features critical to achieving optimal performance. In addition, the findings reinforce the conclusions of previous research, which found that models trained with GPT-2 embeddings consistently outperformed neural networks trained with other embeddings. The fact that this holds even when data snooping is introduced into the embedding model indicates GPT-2's robustness in representing complex code features, even under less-than-ideal conditions.

Zhenghao Gao, Shengjie Xu, Meixi Chen et al.

Contemporary adversarial attack methods face significant limitations in cross-model transferability and practical applicability. We present Watertox, an elegant adversarial attack framework achieving remarkable effectiveness through architectural diversity and precision-controlled perturbations. Our two-stage Fast Gradient Sign Method combines uniform baseline perturbations ($ε_1 = 0.1$) with targeted enhancements ($ε_2 = 0.4$). The framework leverages an ensemble of complementary architectures, from VGG to ConvNeXt, synthesizing diverse perspectives through an innovative voting mechanism. Against state-of-the-art architectures, Watertox reduces model accuracy from 70.6% to 16.0%, with zero-shot attacks achieving up to 98.8% accuracy reduction against unseen architectures. These results establish Watertox as a significant advancement in adversarial methodologies, with promising applications in visual security systems and CAPTCHA generation.

Lianying Zhao, He Shuang, Shengjie Xu et al.

In recent years, there have emerged many new hardware mechanisms for improving the security of our computer systems. Hardware offers many advantages over pure software approaches: immutability of mechanisms to software attacks, better execution and power efficiency and a smaller interface allowing it to better maintain secrets. This has given birth to a plethora of hardware mechanisms providing trusted execution environments (TEEs), support for integrity checking and memory safety and widespread uses of hardware roots of trust. In this paper, we systematize these approaches through the lens of abstraction. Abstraction is key to computing systems, and the interface between hardware and software contains many abstractions. We find that these abstractions, when poorly designed, can both obscure information that is needed for security enforcement, as well as reveal information that needs to be kept secret, leading to vulnerabilities. We summarize such vulnerabilities and discuss several research trends of this area.