arXiv subjects

Shikui Tu

Publications and source records attributed to Shikui Tu.

At least 19 recordsLinked to original sources

arXiv2026

Fused Bayesian Flow Networks for Dual-Target Molecular Design

Dual-target drug design aims to generate 3D molecules that can simultaneously interact with two target proteins, offering a promising route for discovering polypharmacological compounds against complex diseases. While recent generative models have shown encouraging performance in single-target drug design, existing dual-target approaches either focus on sequence generation or introduce an additional predictive drift term into the diffusion-based generative trajectory, which limits their ability to fully integrate feature information from both targets. We propose FusedBFN, a fused Bayesian flow network (BFN) for dual-target molecular design. FusedBFN formulates dual-target generation as distribution fusion in a unified continuous parameter space and employs a product-of-experts formulation to incorporate dual-target information throughout the generative process. To address the scarcity of dual-target structural data, we leverage a pretrained target-aware BFN model as the shared backbone. We further introduce a chemically aware prior-based alignment method and a prior-free pocket alignment strategy to construct aligned dual-target contexts. Extensive experiments demonstrate that FusedBFN generates molecules with strong binding affinity toward dual targets while maintaining favorable molecular properties.

cs.LG↗

arXiv2026

PepLLM: ESM-Guided Llama for Structured Protein-Peptide Binding Interface Analysis

Protein-peptide interactions are central to cellular regulation and peptide-based drug discovery, yet existing computational methods mainly focus on interaction classification, binding-site prediction, or peptide binder generation. These formulations provide limited insight into the physicochemical mechanisms that determine how a peptide binds to a protein. In this work, we introduce \textbf{PepLLM}, an instruction-tuned framework for structured protein-peptide interface understanding. Given protein-peptide sequences, PepLLM generates a machine-readable JSON annotation describing multiple interface properties, including peptide burial state, hydrogen-bond density, salt-bridge presence, hotspot residues, hydrophobicity, and electrostatic complementarity. To support this task, we construct a new protein-peptide interface dataset by integrating structural interface analysis, solvent-accessible surface area computation, hydrophobic burial estimation, electrostatic potential calculation, and redundancy-aware data splitting. PepLLM connects a pretrained ESM encoder with a LLaMA decoder through a nonlinear modality adapter. The adapted ESM residue embeddings are injected into the LLaMA prompt as continuous soft tokens via placeholder-token replacement, enabling the decoder to generate structured interface annotations under instruction tuning. By moving beyond single-label prediction toward multi-property and mechanism-aware generation, PepLLM establishes a new task and modeling paradigm for interpretable protein-peptide interface analysis.

q-bio.BM↗

arXiv2026

Fine-Tuning Diffusion Models for Molecular Generation via Reinforcement Learning and Fast Sampling

Generating molecules that simultaneously satisfy drug-like properties and conform to the 3D structure of a target protein is a core challenge in structure-based drug design (SBDD). Existing generative approaches, however, often rely on costly post-hoc processing during Sampling or require carefully curated datasets during training, yet still achieve modest gains. These limitations are especially pronounced in multi-objective settings, where balancing conflicting criteria remains a core challenge. To address these challenges, We propose FTDiff, a reinforcement learning fine-tuning framework tailored for diffusion-based molecular generation under structural constraints. To ensure stable and sample-efficient optimization, FTDiff adopts a group relative policy optimization (GRPO) style strategy. Furthermore, FTDiff builds upon a time-free pretrained diffusion model and incorporates a fast sampling mechanism that reduces the number of denoising steps, significantly accelerating both training and inference while maintaining generation quality. By optimizing a fixed threshold-aware reward, FTDiff effectively guides the model to produce valid, diverse, and high- quality molecules that balance multiple drug design objectives. Extensive experiments on benchmark datasets demonstrate that FTDiff consistently outperforms prior methods, without requiring expensive post-hoc optimization or intricate data engineering.

cs.LG↗

arXiv2026

DS2SC-Agent: A Multi-Agent Automated Pipeline for Rapid Chiplet Model Generation

Constructing behavioral-level chiplet models (e.g., SystemC) is crucial for early-stage heterogeneous architecture exploration. Traditional manual modeling is notoriously time-consuming and error-prone. Recently, Large Language Models (LLMs) have demonstrated immense potential in automating hardware code generation. However, existing LLM-assisted design frameworks predominantly target highly structured or well-defined design specifications. In practical engineering scenarios, raw datasheets typically encompass lengthy, complex, and highly unstructured information. Consequently, reliable code generation directly from these raw datasheets suffers from severe challenges, including context vanishing and logical hallucinations.To overcome this critical bottleneck, this paper proposes DS2SC-Agent(Datasheet-to-SystemC-Agent): the first end-to-end, fully automated generation pipeline that translates raw datasheets directly into SystemC chiplet models. This system establishes a highly efficient multi-agent collaborative framework. By decoupling the intricate modeling tasks, the proposed pipeline orchestrates a fully automated workflow encompassing unstructured long-document parsing, SystemC core code construction, testbench stimulus generation, and adaptive closed-loop debugging. We comprehensively evaluate the proposed framework on representative single-function chiplets across the analog, digital, and radio frequency (RF) domains--specifically, a Limiting Amplifier (LA), a Fast Fourier Transform (FFT) module, and a Power Amplifier (PA). The evaluation demonstrates that our pipeline seamlessly processes complex real-world datasheets to consistently generate functionally correct SystemC models. This provides a highly efficient and reliable paradigm for agile model library construction while drastically minimizing manual intervention.

cs.AR↗

arXiv2026

UniRank: End-to-End Domain-Specific Reranking of Hybrid Text-Image Candidates

Reranking is a critical component in many information retrieval pipelines. Despite remarkable progress in text-only settings, multimodal reranking remains challenging, particularly when the candidate set contains hybrid text and image items. A key difficulty is the modality gap: a text reranker is intrinsically closer to text candidates than to image candidates, leading to biased and suboptimal cross-modal ranking. Vision-language models (VLMs) mitigate this gap through strong cross-modal alignment and have recently been adopted to build multimodal rerankers. However, most VLM-based rerankers encode all candidates as images, and treating text as images introduces substantial computational overhead. Meanwhile, existing open-source multimodal rerankers are typically trained on general-domain data and often underperform in domain-specific scenarios. To address these limitations, we propose UniRank, a VLM-based reranking framework that natively scores and orders hybrid text-image candidates without any modality conversion. Building on this hybrid scoring interface, UniRank provides an end-to-end domain adaptation pipeline that includes: (1) an instruction-tuning stage that learns calibrated cross-modal relevance scoring by mapping label-token likelihoods to a unified scalar score; and (2) a hard-negative-driven preference alignment stage that constructs in-domain pairwise preferences and performs query-level policy optimization through reinforcement learning from human feedback (RLHF). Extensive experiments on scientific literature retrieval and design patent search demonstrate that UniRank consistently outperforms state-of-the-art baselines, improving Recall@1 by 8.9% and 7.3%, respectively.

cs.IR↗

arXiv2026

Factored Causal Representation Learning for Robust Reward Modeling in RLHF

A reliable reward model is essential for aligning large language models with human preferences through reinforcement learning from human feedback. However, standard reward models are susceptible to spurious features that are not causally related to human labels. This can lead to reward hacking, where high predicted reward does not translate into better behavior. In this work, we address this problem from a causal perspective by proposing a factored representation learning framework that decomposes the model's contextual embedding into (1) causal factors that are sufficient for reward prediction and (2) non-causal factors that capture reward-irrelevant attributes such as length or sycophantic bias. The reward head is then constrained to depend only on the causal component. In addition, we introduce an adversarial head trained to predict reward from the non-causal factors, while applying gradient reversal to discourage them from encoding reward-relevant information. Experiments on both mathematical and dialogue tasks demonstrate that our method learns more robust reward models and consistently improves downstream RLHF performance over state-of-the-art baselines. Analyses on length and sycophantic bias further validate the effectiveness of our method in mitigating reward hacking behaviors.

cs.LG↗

arXiv2025

Generative design and validation of therapeutic peptides for glioblastoma based on a potential target ATP5A

Glioblastoma (GBM) remains the most aggressive tumor, urgently requiring novel therapeutic strategies. Here, we present a dry-to-wet framework combining generative modeling and experimental validation to optimize peptides targeting ATP5A, a potential peptide-binding protein for GBM. Our framework introduces the first lead-conditioned generative model, which focuses exploration on geometrically relevant regions around lead peptides and mitigates the combinatorial complexity of de novo methods. Specifically, we propose POTFlow, a \underline{P}rior and \underline{O}ptimal \underline{T}ransport-based \underline{Flow}-matching model for peptide optimization. POTFlow employs secondary structure information (e.g., helix, sheet, loop) as geometric constraints, which are further refined by optimal transport to produce shorter flow paths. With this design, our method achieves state-of-the-art performance compared with five popular approaches. When applied to GBM, our method generates peptides that selectively inhibit cell viability and significantly prolong survival in a patient-derived xenograft (PDX) model. As the first lead peptide-conditioned flow matching model, POTFlow holds strong potential as a generalizable framework for therapeutic peptide design.

q-bio.BM↗

arXiv2025

Full-Atom Peptide Design via Riemannian-Euclidean Bayesian Flow Networks

Diffusion and flow matching models have recently emerged as promising approaches for peptide binder design. Despite their progress, these models still face two major challenges. First, categorical sampling of discrete residue types collapses their continuous parameters into onehot assignments, while continuous variables (e.g., atom positions) evolve smoothly throughout the generation process. This mismatch disrupts the update dynamics and results in suboptimal performance. Second, current models assume unimodal distributions for side-chain torsion angles, which conflicts with the inherently multimodal nature of side chain rotameric states and limits prediction accuracy. To address these limitations, we introduce PepBFN, the first Bayesian flow network for full atom peptide design that directly models parameter distributions in fully continuous space. Specifically, PepBFN models discrete residue types by learning their continuous parameter distributions, enabling joint and smooth Bayesian updates with other continuous structural parameters. It further employs a novel Gaussian mixture based Bayesian flow to capture the multimodal side chain rotameric states and a Matrix Fisher based Riemannian flow to directly model residue orientations on the $\mathrm{SO}(3)$ manifold. Together, these parameter distributions are progressively refined via Bayesian updates, yielding smooth and coherent peptide generation. Experiments on side chain packing, reverse folding, and binder design tasks demonstrate the strong potential of PepBFN in computational peptide design.

cs.LG↗

arXiv2025

Text to Sketch Generation with Multi-Styles

Recent advances in vision-language models have facilitated progress in sketch generation. However, existing specialized methods primarily focus on generic synthesis and lack mechanisms for precise control over sketch styles. In this work, we propose a training-free framework based on diffusion models that enables explicit style guidance via textual prompts and referenced style sketches. Unlike previous style transfer methods that overwrite key and value matrices in self-attention, we incorporate the reference features as auxiliary information with linear smoothing and leverage a style-content guidance mechanism. This design effectively reduces content leakage from reference sketches and enhances synthesis quality, especially in cases with low structural similarity between reference and target sketches. Furthermore, we extend our framework to support controllable multi-style generation by integrating features from multiple reference sketches, coordinated via a joint AdaIN module. Extensive experiments demonstrate that our approach achieves high-quality sketch generation with accurate style alignment and improved flexibility in style control. The official implementation of M3S is available at https://github.com/CMACH508/M3S.

cs.CV↗

arXiv2025

Prior-Guided Flow Matching for Target-Aware Molecule Design with Learnable Atom Number

Structure-based drug design (SBDD), aiming to generate 3D molecules with high binding affinity toward target proteins, is a vital approach in novel drug discovery. Although recent generative models have shown great potential, they suffer from unstable probability dynamics and mismatch between generated molecule size and the protein pockets geometry, resulting in inconsistent quality and off-target effects. We propose PAFlow, a novel target-aware molecular generation model featuring prior interaction guidance and a learnable atom number predictor. PAFlow adopts the efficient flow matching framework to model the generation process and constructs a new form of conditional flow matching for discrete atom types. A protein-ligand interaction predictor is incorporated to guide the vector field toward higher-affinity regions during generation, while an atom number predictor based on protein pocket information is designed to better align generated molecule size with target geometry. Extensive experiments on the CrossDocked2020 benchmark show that PAFlow achieves a new state-of-the-art in binding affinity (up to -8.31 Avg. Vina Score), simultaneously maintains favorable molecular properties.

cs.LG↗

arXiv2025

Hallucination-Resistant Relation Extraction via Dependency-Aware Sentence Simplification and Two-tiered Hierarchical Refinement

Relation extraction (RE) enables the construction of structured knowledge for many downstream applications. While large language models (LLMs) have shown great promise in this task, they often struggle to reliably determine whether a relation exists, particularly in sentences with complex syntax or subtle semantics. For instance, we find that Qwen2.5-14B-Instruct incorrectly predicts a relation in 96.9% of NO-RELATION instances on SciERC, revealing a severe hallucination problem. To address these challenges, we propose DEPTH, a framework that integrates Dependency-aware sEntence simPlification and Two-tiered Hierarchical refinement into the relation extraction pipeline. Given a sentence and its candidate entity pairs, DEPTH operates in two stages: (1) the Grounding module extracts relations for each pair by leveraging their shortest dependency path, distilling the sentence into a minimal yet coherent relational context that reduces syntactic noise while preserving key semantics; (2) the Refinement module aggregates all local predictions and revises them based on a holistic understanding of the sentence, correcting omissions and inconsistencies. We further introduce a causality-driven reward model that mitigates reward hacking by disentangling spurious correlations, enabling robust fine-tuning via reinforcement learning with human feedback. Experiments on eight well-established benchmarks demonstrate that DEPTH reduces the average hallucination rate to 7.9% while achieving a 9.3% improvement in average F1 score over existing LLM-based extraction baselines.

cs.CL↗

arXiv2025

THFlow: A Temporally Hierarchical Flow Matching Framework for 3D Peptide Design

Deep generative models provide a promising approach to de novo 3D peptide design. Most of them jointly model the distributions of peptide's position, orientation, and conformation, attempting to simultaneously converge to the target pocket. However, in the early stage of docking, optimizing conformation-only modalities such as rotation and torsion can be physically meaningless, as the peptide is initialized far from the protein pocket and no interaction field is present. We define this problem as the multimodal temporal inconsistency problem and claim it is a key factor contributing to low binding affinity in generated peptides. To address this challenge, we propose THFlow, a novel flow matching-based multimodal generative model that explicitly models the temporal hierarchy between peptide position and conformation. It employs a polynomial based conditional flow to accelerate positional convergence early on, and later aligns it with rotation and torsion for coordinated conformation refinement under the emerging interaction field. Additionally, we incorporate interaction-related features, such as polarity, to further enhance the model's understanding of peptide-protein binding. Extensive experiments demonstrate that THFlow outperforms existing methods in generating peptides with superior stability, affinity, and diversity, offering an effective and accurate solution for advancing peptide-based therapeutic development.

q-bio.QM↗

arXiv2024

Boosting Efficiency in Task-Agnostic Exploration through Causal Knowledge

The effectiveness of model training heavily relies on the quality of available training resources. However, budget constraints often impose limitations on data collection efforts. To tackle this challenge, we introduce causal exploration in this paper, a strategy that leverages the underlying causal knowledge for both data collection and model training. We, in particular, focus on enhancing the sample efficiency and reliability of the world model learning within the domain of task-agnostic reinforcement learning. During the exploration phase, the agent actively selects actions expected to yield causal insights most beneficial for world model training. Concurrently, the causal knowledge is acquired and incrementally refined with the ongoing collection of data. We demonstrate that causal exploration aids in learning accurate world models using fewer data and provide theoretical guarantees for its convergence. Empirical experiments, on both synthetic data and real-world applications, further validate the benefits of causal exploration.

cs.LG↗

arXiv2024

Towards Generalizable Reinforcement Learning via Causality-Guided Self-Adaptive Representations

General intelligence requires quick adaption across tasks. While existing reinforcement learning (RL) methods have made progress in generalization, they typically assume only distribution changes between source and target domains. In this paper, we explore a wider range of scenarios where not only the distribution but also the environment spaces may change. For example, in the CoinRun environment, we train agents from easy levels and generalize them to difficulty levels where there could be new enemies that have never occurred before. To address this challenging setting, we introduce a causality-guided self-adaptive representation-based approach, called CSR, that equips the agent to generalize effectively across tasks with evolving dynamics. Specifically, we employ causal representation learning to characterize the latent causal variables within the RL system. Such compact causal representations uncover the structural relationships among variables, enabling the agent to autonomously determine whether changes in the environment stem from distribution shifts or variations in space, and to precisely locate these changes. We then devise a three-step strategy to fine-tune the causal model under different scenarios accordingly. Empirical experiments show that CSR efficiently adapts to the target domains with only a few samples and outperforms state-of-the-art baselines on a wide range of scenarios, including our simulated environments, CartPole, CoinRun and Atari games.

cs.LG↗

arXiv2023

PFB-Diff: Progressive Feature Blending Diffusion for Text-driven Image Editing

Diffusion models have demonstrated their ability to generate diverse and high-quality images, sparking considerable interest in their potential for real image editing applications. However, existing diffusion-based approaches for local image editing often suffer from undesired artifacts due to the latent-level blending of the noised target images and diffusion latent variables, which lack the necessary semantics for maintaining image consistency. To address these issues, we propose PFB-Diff, a Progressive Feature Blending method for Diffusion-based image editing. Unlike previous methods, PFB-Diff seamlessly integrates text-guided generated content into the target image through multi-level feature blending. The rich semantics encoded in deep features and the progressive blending scheme from high to low levels ensure semantic coherence and high quality in edited images. Additionally, we introduce an attention masking mechanism in the cross-attention layers to confine the impact of specific words to desired regions, further improving the performance of background editing and multi-object replacement. PFB-Diff can effectively address various editing tasks, including object/background replacement and object attribute editing. Our method demonstrates its superior performance in terms of editing accuracy and image quality without the need for fine-tuning or training. Our implementation is available at https://github.com/CMACH508/PFB-Diff.

cs.CV↗

arXiv2022

Linking Sketch Patches by Learning Synonymous Proximity for Graphic Sketch Representation

Graphic sketch representations are effective for representing sketches. Existing methods take the patches cropped from sketches as the graph nodes, and construct the edges based on sketch's drawing order or Euclidean distances on the canvas. However, the drawing order of a sketch may not be unique, while the patches from semantically related parts of a sketch may be far away from each other on the canvas. In this paper, we propose an order-invariant, semantics-aware method for graphic sketch representations. The cropped sketch patches are linked according to their global semantics or local geometric shapes, namely the synonymous proximity, by computing the cosine similarity between the captured patch embeddings. Such constructed edges are learnable to adapt to the variation of sketch drawings, which enable the message passing among synonymous patches. Aggregating the messages from synonymous patches by graph convolutional networks plays a role of denoising, which is beneficial to produce robust patch embeddings and accurate sketch representations. Furthermore, we enforce a clustering constraint over the embeddings jointly with the network learning. The synonymous patches are self-organized as compact clusters, and their embeddings are guided to move towards their assigned cluster centroids. It raises the accuracy of the computed synonymous proximity. Experimental results show that our method significantly improves the performance on both controllable sketch synthesis and sketch healing.

cs.CV↗

arXiv2022

IA-FaceS: A Bidirectional Method for Semantic Face Editing

Semantic face editing has achieved substantial progress in recent years. Known as a growingly popular method, latent space manipulation performs face editing by changing the latent code of an input face to liberate users from painting skills. However, previous latent space manipulation methods usually encode an entire face into a single low-dimensional embedding, which constrains the reconstruction capacity and the control flexibility of facial components, such as eyes and nose. This paper proposes IA-FaceS as a bidirectional method for disentangled face attribute manipulation as well as flexible, controllable component editing without the need for segmentation masks or sketches in the original image. To strike a balance between the reconstruction capacity and the control flexibility, the encoder is designed as a multi-head structure to yield embeddings for reconstruction and control, respectively: a high-dimensional tensor with spatial properties for consistent reconstruction and four low-dimensional facial component embeddings for semantic face editing. Manipulating the separate component embeddings can help achieve disentangled attribute manipulation and flexible control of facial components. To further disentangle the highly-correlated components, a component adaptive modulation (CAM) module is proposed for the decoder. The semantic single-eye editing is developed for the first time without any input visual guidance, such as segmentation masks or sketches. According to the experimental results, IA-FaceS establishes a good balance between maintaining image details and performing flexible face manipulation. Both quantitative and qualitative results indicate that the proposed method outperforms the other techniques in reconstruction, face attribute manipulation, and component transfer.

cs.CV↗

arXiv2021

Deep Rival Penalized Competitive Learning for Low-resolution Face Recognition

Current face recognition tasks are usually carried out on high-quality face images, but in reality, most face images are captured under unconstrained or poor conditions, e.g., by video surveillance. Existing methods are featured by learning data uncertainty to avoid overfitting the noise, or by adding margins to the angle or cosine space of the normalized softmax loss to penalize the target logit, which enforces intra-class compactness and inter-class discrepancy. In this paper, we propose a deep Rival Penalized Competitive Learning (RPCL) for deep face recognition in low-resolution (LR) images. Inspired by the idea of the RPCL, our method further enforces regulation on the rival logit, which is defined as the largest non-target logit for an input image. Different from existing methods that only consider penalization on the target logit, our method not only strengthens the learning towards the target label, but also enforces a reverse direction, i.e., becoming de-learning, away from the rival label. Comprehensive experiments demonstrate that our method improves the existing state-of-the-art methods to be very robust for LR face recognition.

cs.CV↗