Yining Qian

Tao Tan, Yining Qian, Ang Lv et al.

Large language models (LLMs) enhanced with retrieval-augmented generation (RAG) have introduced a new paradigm for web search. However, the limited context awareness of LLMs degrades their performance on RAG tasks. Existing methods to enhance context awareness are often inefficient, incurring time or memory overhead during inference, and many are tailored to specific position embeddings. In this paper, we propose Position-Embedding-Agnostic attention Re-weighting (PEAR), which enhances the context awareness of LLMs with zero inference overhead. Specifically, on a proxy task focused on context copying, we first detect heads which suppress the models' context awareness thereby diminishing RAG performance. To weaken the impact of these heads, we re-weight their outputs with learnable coefficients. The LLM (with frozen parameters) is optimized by adjusting these coefficients to minimize loss on the proxy task. As a result, the coefficients are optimized to values less than one, thereby reducing their tendency to suppress RAG performance. During inference, the optimized coefficients are fixed to re-weight these heads, regardless of the specific task at hand. Our proposed PEAR offers two major advantages over previous approaches: (1) It introduces zero additional inference overhead in terms of memory usage or inference time, while outperforming competitive baselines in accuracy and efficiency across various RAG tasks. (2) It is independent of position embedding algorithms, ensuring broader applicability.

Yining Qian, Pengjie Wang, Yixiao Li et al.

Predicting drug-target affinity is fundamental to virtual screening and lead optimization. However, existing deep models often suffer from representation collapse in stringent cold-start regimes, where the scarcity of labels and domain shifts prevent the learning of transferable pharmacophores and binding motifs. In this paper, we propose Co-Diffusion, a novel affinity-aware framework that redefines DTA prediction as a constrained latent denoising process to enhance generalization. Co-Diffusion employs a two-stage paradigm: Stage I establishes an affinity-steered latent manifold by aligning drug and target embeddings under an explicit supervised objective, ensuring that the latent space reflects the intrinsic binding landscape. Stage II introduces modality-specific latent diffusion as a stochastic perturb-and-denoise regularizer, forcing the model to recover consistent affinity semantics from noisy structural representations. This approach effectively mitigates the reconstruction-regression conflict common in generative DTA models. Theoretically, we show that Co-Diffusion maximizes a variational lower bound on the joint likelihood of drug structures, protein sequences, and binding strength. Extensive experiments across multiple benchmarks demonstrate that Co-Diffusion significantly outperforms state-of-the-art baselines, particularly yielding superior zero-shot generalization on unseen molecular scaffolds and novel protein families-paving a robust path for in silico drug prioritization in unexplored chemical spaces.

Yining Qian, Lijie Su, Meiling Xu et al.

Predicting protein secondary structure is essential for understanding protein function and advancing drug discovery. However, the intricate sequence-structure relationship poses significant challenges for accurate modeling. To address these, we propose MOGP-MMF, a multi-objective genetic programming framework that reformulates PSSP as an automated optimization task focused on feature selection and fusion. Specifically, MOGP-MMF introduces a multi-view multi-level representation strategy that integrates evolutionary, semantic, and newly introduced structural views to capture the comprehensive protein folding logic. Leveraging an enriched operator set, the framework evolves both linear and nonlinear fusion functions, effectively capturing high-order feature interactions while reducing fusion complexity. To resolve the accuracy-complexity trade-off, an improved multi-objective GP algorithm is developed, incorporating a knowledge transfer mechanism that utilizes prior evolutionary experience to guide the population toward global optima. Extensive experiments across seven benchmark datasets demonstrate that MOGP-MMF surpasses state-of-the-art methods, particularly in Q8 accuracy and structural integrity. Furthermore, MOGP-MMF generates a diverse set of non-dominated solutions, offering flexible model selection schemes for various practical application scenarios. The source code is available on GitHub: https://github.com/qian-ann/MOGP-MMF/tree/main.

Yiming Gao, Liuyi Xu, Pengshan Cui et al.

Accurate identification of protein-nucleotide binding sites is fundamental to deciphering molecular mechanisms and accelerating drug discovery. However, current computational methods often struggle with suboptimal performance due to inadequate feature representation and rigid fusion mechanisms, which hinder the effective exploitation of cross-task information synergy. To bridge this gap, we propose MTGA-MGE, a framework that integrates a Multi-Task Genetic Algorithm with Multi-Granularity Encoding to enhance binding site prediction. Specifically, we develop a Multi-Granularity Encoding (MGE) network that synergizes multi-scale convolutions and self-attention mechanisms to distill discriminative signals from high-dimensional, redundant biological data. To overcome the constraints of static fusion, a genetic algorithm is employed to adaptively evolve task-specific fusion strategies, thereby effectively improving model generalization. Furthermore, to catalyze collaborative learning, we introduce an External-Neighborhood Mechanism (ENM) that leverages biological similarities to facilitate targeted information exchange across tasks. Extensive evaluations on fifteen nucleotide datasets demonstrate that MTGA-MGE not only establishes a new state-of-the-art in data-abundant, high-resource scenarios but also maintains a robust competitive edge in rare, low-resource regimes, presenting a highly adaptive scheme for decoding complex protein-ligand interactions in the post-genomic era.

Ang Lv, Ruobing Xie, Yining Qian et al.

Mixture-of-Experts (MoE) models mostly use a router to assign tokens to specific expert modules, activating only partial parameters and often outperforming dense models. We argue that the separation between the router's decision-making and the experts' execution is a critical yet overlooked issue, leading to suboptimal expert selection and ineffective learning. To address this, we propose Autonomy-of-Experts (AoE), a novel MoE paradigm in which experts autonomously select themselves to process inputs. AoE is based on the insight that an expert is aware of its own capacity to effectively process a token, an awareness reflected in the scale of its internal activations. In AoE, routers are removed; instead, experts pre-compute internal activations for inputs and are ranked based on their activation norms. Only the top-ranking experts proceed with the forward pass, while the others abort. The overhead of pre-computing activations is reduced through a low-rank weight factorization. This self-evaluating-then-partner-comparing approach ensures improved expert selection and effective learning. We pre-train language models having 700M up to 4B parameters, demonstrating that AoE outperforms traditional MoE models with comparable efficiency.

Shaokuan Wang, Pengshan Cui, Yining Qian et al.

Intrinsically disordered regions of proteins play a crucial role in cell signaling and drug discovery. However, their high structural flexibility makes accurate residue-level prediction challenging. Existing methods often rely on single-view representations or rigid manual fusion strategies, which fail to effectively balance the complex interplay between local amino acid preferences and long-range sequence patterns. To address these limitations, we propose D2MOE, a Dual-View Multiscale Features and Multi-objective Evolutionary Algorithm, which consists of two stages. First, a dual-view multiscale feature extraction method is introduced. This method integrates evolutionary views with deep semantic views and employs multiscale extractors to capture structural information across diverse receptive fields. Second, a multi-objective evolutionary algorithm is designed to adaptively discover optimal fusion architectures. By co-evolving discrete feature selection and continuous fusion weights, the algorithm adaptively explores optimal cross-feature architectures to enhance predictive accuracy while maintaining model compactness. Experimental results across three benchmark datasets demonstrate that D2MOE consistently outperforms state-of-the-art methods. D2MOE combines the feature extraction capabilities of deep learning with the global search advantages of evolutionary algorithms, enabling efficient feature integration without manual design, and providing a robust computational tool for protein disorder prediction.

Zihan Dun, Liuyi Xu, An-Yang Lu et al.

Drug--target affinity prediction is pivotal for accelerating drug discovery, yet existing methods suffer from significant performance degradation in realistic cold-start scenarios (unseen drugs/targets/pairs), primarily driven by overfitting to training instances and information loss from irrelevant target sequences. In this paper, we propose LaPro-DTA, a framework designed to achieve robust and generalizable DTA prediction. To tackle overfitting, we devise a latent dual-view drug representation mechanism. It synergizes an instance-level view to capture fine-grained substructures with stochastic perturbation and a distribution-level view to distill generalized chemical scaffolds via semantic remapping, thereby enforcing the model to learn transferable structural rules rather than memorizing specific samples. To mitigate information loss, we introduce a salient protein feature extraction strategy using pattern-aware top-$k$ pooling, which effectively filters background noise and isolates high-response bioactive regions. Furthermore, a cross-view multi-head attention mechanism fuses these purified features to model comprehensive interactions. Extensive experiments on benchmark datasets demonstrate that LaPro-DTA significantly outperforms state-of-the-art methods, achieving an 8\% MSE reduction on the Davis dataset in the challenging unseen-drug setting, while offering interpretable insights into binding mechanisms.

Zhaolu Dong, Shan Huang, Simiao Ma et al.

Deep Reinforcement learning is a branch of unsupervised learning in which an agent learns to act based on environment state in order to maximize its total reward. Deep reinforcement learning provides good opportunity to model the complexity of portfolio choice in high-dimensional and data-driven environment by leveraging the powerful representation of deep neural networks. In this paper, we build a portfolio management system using direct deep reinforcement learning to make optimal portfolio choice periodically among S\&P500 underlying stocks by learning a good factor representation (as input). The result shows that an effective learning of market conditions and optimal portfolio allocations can significantly outperform the average market.