Ying Li

Tinghui Jin, Kedu Jin, Ying Li et al.

Predicting the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of small molecules remains a major challenge in drug discovery. Here, we present MEGA-CL, a foundation graph neural network framework for universal molecular ADMET prediction. MEGA-CL integrates self-supervised contrastive learning with a multi-head external attention mechanism and an enhanced message-passing architecture, enabling simultaneous modeling of local chemical substructures and global inter-graph relationships while mitigating over-smoothing effects commonly observed in deep graph networks. Across 13 benchmark datasets and 21 downstream ADMET tasks, MEGA-CL consistently outperforms state-of-the-art baseline models. In particular, the framework demonstrates robust performance on challenging regression tasks, including clearance (CL) and steady-state volume of distribution (VDss), while maintaining strong generalization ability in independent external validation. Clinically relevant predictive accuracy was achieved, with more than 75% of predictions falling within a 3-fold error range. In an external evaluation on 18 novel compounds derived from recently approved FDA drugs, over 50% of human liver microsome clearance (HLMC) predictions were within a 2-fold error range. To further assess its practical applicability, MEGA-CL was prospectively evaluated on three preclinical drug candidates using in vitro hepatic microsomal metabolism assays and CYP450 inhibition assays guided by model predictions. The predicted HLMC values for all candidates were within 2.5-fold of the experimentally measured values, and 73.3% of CYP450 inhibition endpoints (11/15) were correctly classified. These results demonstrate the potential of MEGA-CL as a generalizable framework for accelerating in silico ADMET evaluation and early-stage drug candidate optimization.

Minghua He, Tong Jia, Lingzhe Zhang et al.

Log-based fault diagnosis is crucial for runtime debugging and maintenance. Existing fault diagnosis methods use language models pre-trained on natural language (PLMs) for log representation. However, system faults are reflected in the multi-level structure of system logs. PLMs pre-trained on natural language struggle to comprehensively capture multi-level fault information, failing to meet the requirements of fault diagnosis. We refer to this information as fallibility representations. To address this problem, we propose a novel log representation learning method, Bifrost. It draws inspiration from the log analysis experience of Site Reliability Engineers and meticulously designs strategies based on self-supervised contrastive learning to learn the fallibility representations of logs. Across three public systems and one industrial ML-as-a-Service system, the log representations produced by Bifrost outperform existing PLMs by average margins of 9.83% in F1 for anomaly detection, 18.28% in HR@k for root cause localization, and 20.88% in Macro-F1 for fault identification.