Xuanbai Ren, Luoda Tan, Pei Liu, Tengfei Ma, Xiangzheng Fu, Longyue Wang, Yiping Liu, Xiangxiang Zeng. Proceedings of the 64th Annual Meeting of the Association for Computational Linguistics (Volume 1: Long Papers). 2026.

Molecular design inherently involves the optimization of multiple conflicting objectives, such as enhancing bio-activity and ensuring synthesizability. Evaluating these objectives often requires resource-intensive computations or physical experiments. Current molecular design methodologies typically approximate the Pareto set using a limited number of molecules. In this paper, we present an innovative approach, called Multi-Objective Molecular Design through Learning Latent Pareto Set (MLPS). MLPS initially utilizes an encoder-decoder model to seamlessly transform the discrete chemical space into a continuous latent space. We then employ local Bayesian optimization models to efficiently search for local optimal solutions (i.e., molecules) within predefined trust regions. Using surrogate objective values derived from these local models, we train a global Pareto set learning model to understand the mapping between direction vectors (called “preferences”) in the objective space and the entire Pareto set in the continuous latent space. Both the global Pareto set learning model and local Bayesian optimization models collaborate to discover high-quality solutions and adapt the trust regions dynamically. Our work is an effective endeavor towards learning the Pareto set for multi-objective molecular design, providing decision-makers with the capability to fine-tune their preferences and thoroughly explore the Pareto set. Experimental results demonstrate that MLPS achieves state-of-the-art performance across various multi-objective scenarios, encompassing diverse objective types and varying numbers of objectives. The effectiveness of MLPS was further validated through real-world challenges in discovering antifungal peptides with low toxicity and high activity.

Identifying drug-drug interactions (DDIs) is critical for ensuring drug safety and advancing drug development, a topic that has garnered significant research interest. While existing methods have made considerable progress, approaches relying solely on known DDIs face a key challenge when applied to drugs with limited data: insufficient exploration of the space of unlabeled pairwise drugs. To address these issues, we innovatively introduce S$^2$VM, a Self-supervised Visual pretraining framework for pair-wise Molecules, to fully fuse structural representations and explore the space of drug pairs for DDI prediction. S$^2$VM incorporates the explicit structure and correlations of visual molecules, such as the positional relationships and connectivity between functional substructures. Specifically, we blend the visual fragments of drug pairs into a unified input for joint encoding and then recover molecule-specific visual information for each drug individually. This approach integrates fine-grained structural representations from unlabeled drug pair data. By using visual fragments as anchors, S$^2$VM effectively captures the spatial information of local molecular components within visual molecules, resulting in more comprehensive embeddings of drug pairs. Experimental results show that S$^2$VM achieves state-of-the-art performance on widely used benchmarks, with Macro-F1 score improvements of 4.21% and 3.31%, respectively. Further extensive results and theoretical analysis demonstrate the effectiveness of S$^2$VM for both few-shot and novel drugs.

MOTIVATION: Enhancers are non-coding DNA fragments with high position variability and free scattering. They play an important role in controlling gene expression. As machine learning has become more widely used in identifying enhancers, a number of bioinformatic tools have been developed. Although several models for identifying enhancers and their strengths have been proposed, their accuracy and efficiency have yet to be improved. RESULTS: We propose a two-layer predictor called 'iEnhancer-XG.' It comprises a one-layer predictor (for identifying enhancers) and a second classifier (for their strength) and uses 'XGBoost' as a base classifier and five feature extraction methods, namely, k-Spectrum Profile, Mismatch k-tuple, Subsequence Profile, Position-specific scoring matrix (PSSM) and Pseudo dinucleotide composition (PseDNC). Each method has an independent output. We place the feature vector matrix into the ensemble learning for fusion. This experiment involves the method of 'SHapley Additive explanations' to provide interpretability for the previous black box machine learning methods and improve their credibility. The accuracies of the ensemble learning method are 0.811 (first layer) and 0.657 (second layer). The rigorous 10-fold cross-validation confirms that the proposed method is significantly better than existing technologies. AVAILABILITY AND IMPLEMENTATION: The source code and dataset for the enhancer predictions have been uploaded to https://github.com/jimmyrate/ienhancer-xg. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.