Olfaction lies at the intersection of chemical structure, neural encoding, and linguistic perception, yet existing representation methods fail to fully capture this pathway.Current approaches typically model only isolated segments of the olfactory pathway, overlooking the complete chain from molecule to receptors to linguistic descriptions.Such fragmentation yields learned embeddings that lack both biological grounding and semantic interpretability.We propose NOSE (Neural Olfactory-Semantic Embedding), a representation learning framework that aligns three modalities along the olfactory pathway: molecular structure, receptor sequence, and natural language description.Rather than simply fusing these signals, we decouple their contributions via orthogonal constraints, preserving the unique encoded information of each modality.To address the sparsity of olfactory language, we introduce a weak positive sample strategy to calibrate semantic similarity, preventing erroneous repulsion of similar odors in the feature space.Extensive experiments demonstrate that NOSE achieves state-of-the-art (SOTA) performance and excellent zero-shot generalization, confirming the strong alignment between its representation space and human olfactory intuition.Code and data are available at https://github.com/Xianyusyy/NOSE

Hengxing Cai, Jinhan Dong, Jingjun Tan, Jingcheng Deng, Sihang Li, Zhifeng Gao, Haidong Wang, Zicheng Su, Agachai Sumalee, Renxin Zhong. Proceedings of the 2025 Conference on Empirical Methods in Natural Language Processing. 2025.

Structure-based drug design (SBDD) aims to generate potential drugs that can bind to a target protein and is greatly expedited by the aid of AI techniques in generative models. However, a lack of systematic understanding persists due to the diverse settings, complex implementation, difficult reproducibility, and task singularity. Firstly, the absence of standardization can lead to unfair comparisons and inconclusive insights. To address this dilemma, we propose CBGBench, a comprehensive benchmark for SBDD, that unifies the task as a generative graph completion, analogous to fill-in-the-blank of the 3D complex binding graph. By categorizing existing methods based on their attributes, CBGBench facilitates a modular and extensible framework that implements cutting-edge methods. Secondly, a single de novo molecule generation task can hardly reflect their capabilities. To broaden the scope, we adapt these models to a range of tasks essential in drug design, considered sub-tasks within the graph fill-in-the-blank tasks. These tasks include the generative designation of de novo molecules, linkers, fragments, scaffolds, and sidechains, all conditioned on the structures of protein pockets. Our evaluations are conducted with fairness, encompassing comprehensive perspectives on interaction, chemical properties, geometry authenticity, and substructure validity. We further provide insights with analysis from empirical studies. Our results indicate that there is potential for further improvements on many tasks, with optimization in network architectures, and effective incorporation of chemical prior knowledge. Finally, to lower the barrier to entry and facilitate further developments in the field, we also provide a single [codebase](https://github.com/EDAPINENUT/CBGBench) that unifies the discussed models, data pre-processing, training, sampling, and evaluation.

Molecular pretrained representations (MPR) has emerged as a powerful approach for addressing the challenge of limited supervised data in applications such as drug discovery and material design. While early MPR methods relied on 1D sequences and 2D graphs, recent advancements have incorporated 3D conformational information to capture rich atomic interactions. However, these prior models treat molecules merely as discrete atom sets, overlooking the space surrounding them. We argue from a physical perspective that only modeling these discrete points is insufficient. We first present a simple yet insightful observation: naively adding randomly sampled virtual points beyond atoms can surprisingly enhance MPR performance. In light of this, we propose a principled framework that incorporates the entire 3D space spanned by molecules. We implement the framework via a novel Transformer-based architecture, dubbed SpaceFormer, with three key components: (1)grid-based space discretization; (2)grid sampling/merging; and (3)efficient 3D positional encoding. Extensive experiments show that SpaceFormer significantly outperforms previous 3D MPR models across various downstream tasks with limited data, validating the benefit of leveraging the additional 3D space beyond atoms in MPR models.

Polymer conformation generation is a critical task that enables atomic-level studies of diverse polymer materials. While significant advances have been made in designing conformation generation methods for small molecules and proteins, these methods struggle to generate polymer conformations due to their unique structural characteristics. Meanwhile, the scarcity of polymer conformation datasets further limits progress, making this important area largely unexplored. In this work, we propose PolyConf, a pioneering tailored polymer conformation generation method that leverages hierarchical generative models to unlock new possibilities. Specifically, we decompose the polymer conformation into a series of local conformations (i.e., the conformations of its repeating units), generating these local conformations through an autoregressive model, and then generating their orientation transformations via a diffusion model to assemble them into the complete polymer conformation. Moreover, we develop the first benchmark with a high-quality polymer conformation dataset derived from molecular dynamics simulations to boost related research in this area. The comprehensive evaluation demonstrates that PolyConf consistently outperforms existing conformation generation methods, thus facilitating advancements in polymer modeling and simulation. The whole work is available at https://polyconf-icml25.github.io.

Polymers are high-molecular-weight compounds constructed by the covalent bonding of numerous identical or similar monomers so that their 3D structures are complex yet exhibit unignorable regularity. Typically, the properties of a polymer, such as plasticity, conductivity, bio-compatibility, and so on, are highly correlated with its 3D structure. However, existing polymer property prediction methods heavily rely on the information learned from polymer SMILES sequences (P-SMILES strings) while ignoring crucial 3D structural information, resulting in sub-optimal performance. In this work, we propose MMPolymer, a novel multimodal multitask pretraining framework incorporating polymer 1D sequential and 3D structural information to encourage downstream polymer property prediction tasks. Besides, considering the scarcity of polymer 3D data, we further introduce the "Star Substitution" strategy to extract 3D structural information effectively. During pretraining, in addition to predicting masked tokens and recovering clear 3D coordinates, MMPolymer achieves the cross-modal alignment of latent representations. Then we further fine-tune the pretrained MMPolymer for downstream polymer property prediction tasks in the supervised learning paradigm. Experiments show that MMPolymer achieves state-of-the-art performance in downstream property prediction tasks. Moreover, given the pretrained MMPolymer, utilizing merely a single modality in the fine-tuning phase can also outperform existing methods, showcasing the exceptional capability of MMPolymer in polymer feature extraction and utilization.

In recent years, pretraining models have made significant advancements in the fields of natural language processing (NLP), computer vision (CV), and life sciences. The significant advancements in NLP and CV are predominantly driven by the expansion of model parameters and data size, a phenomenon now recognized as the scaling laws. However, research exploring scaling law in molecular pretraining model remains unexplored. In this work, we present an innovative molecular pretraining model that leverages a two-track transformer to effectively integrate features at the atomic level, graph level, and geometry structure level. Along with this, we systematically investigate the scaling law within molecular pretraining models, examining the power-law correlations between validation loss and model size, dataset size, and computational resources. Consequently, we successfully scale the model to 1.1 billion parameters through pretraining on 800 million conformations, making it the largest molecular pretraining model to date. Extensive experiments show the consistent improvement on the downstream tasks as the model size grows up. The model with 1.1 billion parameters also outperform over existing methods, achieving an average 27\% improvement on the QM9 and 14\% on COMPAS-1D dataset.

Virtual Screening is an essential technique in the early phases of drug discovery, aimed at identifying promising drug candidates from vast molecular libraries. Recently, ligand-based virtual screening has garnered significant attention due to its efficacy in conducting extensive database screenings without relying on specific protein-binding site information. Obtaining binding affinity data for complexes is highly expensive, resulting in a limited amount of available data that covers a relatively small chemical space. Moreover, these datasets contain a significant amount of inconsistent noise. It is challenging to identify an inductive bias that consistently maintains the integrity of molecular activity during data augmentation. To tackle these challenges, we propose S-MolSearch, the first framework to our knowledge, that leverages molecular 3D information and affinity information in semi-supervised contrastive learning for ligand-based virtual screening. % S-MolSearch processes both labeled and unlabeled data, trains molecular structural encoders, and generates soft labels for unlabeled data, drawing on the principles of inverse optimal transport. Drawing on the principles of inverse optimal transport, S-MolSearch efficiently processes both labeled and unlabeled data, training molecular structural encoders while generating soft labels for the unlabeled data. This design allows S-MolSearch to adaptively utilize unlabeled data within the learning process. Empirically, S-MolSearch demonstrates superior performance on widely-used benchmarks LIT-PCBA and DUD-E. It surpasses both structure-based and ligand-based virtual screening methods for AUROC, BEDROC and EF.

During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making.

The predictive learning of spatiotemporal sequences aims to generate future images by learning from the historical context, where the visual dynamics are believed to have modular structures that can be learned with compositional subsystems. This paper models these structures by presenting PredRNN, a new recurrent network, in which a pair of memory cells are explicitly decoupled, operate in nearly independent transition manners, and finally form unified representations of the complex environment. Concretely, besides the original memory cell of LSTM, this network is featured by a zigzag memory flow that propagates in both bottom-up and top-down directions across all layers, enabling the learned visual dynamics at different levels of RNNs to communicate. It also leverages a memory decoupling loss to keep the memory cells from learning redundant features. We further propose a new curriculum learning strategy to force PredRNN to learn long-term dynamics from context frames, which can be generalized to most sequence-to-sequence models. We provide detailed ablation studies to verify the effectiveness of each component. Our approach is shown to obtain highly competitive results on five datasets for both action-free and action-conditioned predictive learning scenarios.

The outbreak of the COVID-19 pandemic has largely influenced the world and our normal daily lives. To combat this pandemic efficiently, governments usually need to coordinate essential resources across multiple regions and adjust intervention polices at the right time, which all call for accurate and robust forecasting of future epidemic trends. However, designing such a forecasting system is non-trivial, since we need to handle all kinds of locations at different administrative levels, which include pretty different epidemic-evolving patterns. Moreover, there are dynamic and volatile correlations of pandemic conditions among these locations, which further enlarge the difficulty in forecasting. With these challenges in mind, we develop a novel spatial-temporal forecasting framework. First, to accommodate all kinds of locations at different administrative levels, we propose a unified hierarchical view, which mimics the aggregation procedure of pandemic statistics. Then, this view motivates us to facilitate joint learning across administrative levels and inspires us to design the cross-level consistency loss as an extra regularization to stabilize model training. Besides, to capture those dynamic and volatile spatial correlations, we design a customized spatial module with adaptive edge gates, which can both reinforce effective messages and disable irrelevant ones. We put this framework into production to help the battle against COVID-19 in the United States. A comprehensive online evaluation across three months demonstrates that our projections are the most competitive ones among all results produced by dozens of international group and even surpass the official ensemble in many cases. We also visualize our unique edge gates to understand the evolvement of spatial correlations and present intuitive case studies. Besides, we open source our implementation at https://github.com/dolphin-zs/HierST to facilitate future research towards better epidemic modeling.

Modern online advertising systems inevitably rely on personalization methods, such as click-through rate (CTR) prediction. Recent progress in CTR prediction enjoys the rich representation capabilities of deep learning and achieves great success in large-scale industrial applications. However, these methods can suffer from lack of exploration. Another line of prior work addresses the exploration-exploitation trade-off problem with contextual bandit methods, which are recently less studied in the industry due to the difficulty in extending their flexibility with deep models. In this paper, we propose a novel Deep Uncertainty-Aware Learning (DUAL) method to learn CTR models based on Gaussian processes, which can provide predictive uncertainty estimations while maintaining the flexibility of deep neural networks. DUAL can be easily implemented on existing models and deployed in real-time systems with minimal extra computational overhead. By linking the predictive uncertainty estimation ability of DUAL to well-known bandit algorithms, we further present DUAL-based Ad-ranking strategies to boost up long-term utilities such as the social welfare in advertising systems. Experimental results on several public datasets demonstrate the effectiveness of our methods. Remarkably, an online A/B test deployed in the Alibaba display advertising platform shows an 8.2% social welfare improvement and an 8.0% revenue lift.

Many real-world applications reveal difficulties in learning classifiers from imbalanced data. The rising big data era has been witnessing more classification tasks with large-scale but extremely imbalance and low-quality datasets. Most of existing learning methods suffer from poor performance or low computation efficiency under such a scenario. To tackle this problem, we conduct deep investigations into the nature of class imbalance, which reveals that not only the disproportion between classes, but also other difficulties embedded in the nature of data, especially, noises and class overlapping, prevent us from learning effective classifiers. Taking those factors into consideration, we propose a novel framework for imbalance classification that aims to generate a strong ensemble by self-paced harmonizing data hardness via under-sampling. Extensive experiments have shown that this new framework, while being very computationally efficient, can lead to robust performance even under highly overlapping classes and extremely skewed distribution. Note that, our methods can be easily adapted to most of existing learning methods (e.g., C4.5, SVM, GBDT and Neural Network) to boost their performance on imbalanced data.

"Silent Speech Interfaces'' (SSI) refers to a system which uses non-audible signals recorded during speech production to perform speech recognition and synthesis tasks. Different approaches have been proposed for the SSI systems. In this paper, we focus on an ultrasound-based SSI. The performance of ultrasound-based SSI system heavily relies on the feature extraction approach. However, most of the previous attempts are often limited to individual frame analysis, and the context information of the image sequence cannot be taken into account. Inspired by the recent success of the recurrent neural network and convolutional auto-encoder, we explore a novel sequential feature extraction approach for SSI system. The architecture can extract spatial and temporal feature from the image sequence, which can be further deployed for the speech recognition and synthetic tasks. By quantitative comparison between different unsupervised feature extraction approaches, the new approach outperforms other methods on the 2010 SSI challenge.

We present PredRNN++, a recurrent network for spatiotemporal predictive learning. In pursuit of a great modeling capability for short-term video dynamics, we make our network deeper in time by leveraging a new recurrent structure named Causal LSTM with cascaded dual memories. To alleviate the gradient propagation difficulties in deep predictive models, we propose a Gradient Highway Unit, which provides alternative quick routes for the gradient flows from outputs back to long-range previous inputs. The gradient highway units work seamlessly with the causal LSTMs, enabling our model to capture the short-term and the long-term video dependencies adaptively. Our model achieves state-of-the-art prediction results on both synthetic and real video datasets, showing its power in modeling entangled motions.

The predictive learning of spatiotemporal sequences aims to generate future images by learning from the historical frames, where spatial appearances and temporal variations are two crucial structures. This paper models these structures by presenting a predictive recurrent neural network (PredRNN). This architecture is enlightened by the idea that spatiotemporal predictive learning should memorize both spatial appearances and temporal variations in a unified memory pool. Concretely, memory states are no longer constrained inside each LSTM unit. Instead, they are allowed to zigzag in two directions: across stacked RNN layers vertically and through all RNN states horizontally. The core of this network is a new Spatiotemporal LSTM (ST-LSTM) unit that extracts and memorizes spatial and temporal representations simultaneously. PredRNN achieves the state-of-the-art prediction performance on three video prediction datasets and is a more general framework, that can be easily extended to other predictive learning tasks by integrating with other architectures.

Based on the adaptive-control technique, this paper deals with the problem of fault-tolerant tracking control for near-space-vehicle (NSV) attitude dynamics. First, Takagi–Sugeno (T–S) fuzzy models are used to describe the NSV attitude dynamics; then, an actuator-fault model is developed. Next, an adaptive fault-tolerant tracking-control scheme is proposed based on the online estimation of actuator faults, in which a compensation control term is introduced in order to reduce the effect of actuator faults. Compared with some existing results of fault-tolerant control (FTC) in nonlinear systems, the technique presented in this paper is not dependent on fault detection and isolation (FDI) mechanism and is easy to implement in aerospace-engineering applications. Finally, simulation results are given to illustrate the effectiveness and potential of the proposed FTC scheme.