arXiv subjects

Fang Wu

Publications and source records attributed to Fang Wu.

At least 73 records · Page 4Linked to original sources

arXiv2025

Lunar Orbital VLBI Experiment: motivation, scientific purposes and status

The Lunar Orbital VLBI Experiment (LOVEX) is a scientific component of the Chinese Lunar Exploration Project (CLEP) Chang'E-7. The spaceborne component of LOVEX is implemented onboard the relay satellite QueQiao-2, which was launched on 2024 March 20, and later placed into an elliptical selenocentric orbit. The LOVEX-specific payload consists of an X-band cryogenic receiver, a hydrogen maser frequency standard, and VLBI data formatting and acquisition electronics. Several components of the QueQiao-2 nominal onboard instrumentation, such as the 4.2-meter antenna, the data storage device, and the downlink communication system, contribute to the overall spaceborne VLBI instrumentation. This allows us to form a space radio telescope capable of co-observing with Earth-based radio telescopes in VLBI mode. In this space VLBI system, the length of the baseline extends up to approximately 380,000 km. This paper presents the LOVEX scientific objectives, architecture, instrumentation, pre-launch tests, in-flight verification and calibration, and the first in-flight detections of interferometric response (''fringes'') achieved through observations of the quasar AO 0235+164 and the Chang'E-6 orbital module, positioned at the Sun-Earth Lagrange point L2. These initial results demonstrate the successful performance of LOVEX, verifying its capability for both astronomical and spacecraft tracking observations at ultra-long VLBI baselines.

astro-ph.IM↗

arXiv2025

Predicting mutational effects on protein binding from folding energy

Accurate estimation of mutational effects on protein-protein binding energies is an open problem with applications in structural biology and therapeutic design. Several deep learning predictors for this task have been proposed, but, presumably due to the scarcity of binding data, these methods underperform computationally expensive estimates based on empirical force fields. In response, we propose a transfer-learning approach that leverages advances in protein sequence modeling and folding stability prediction for this task. The key idea is to parameterize the binding energy as the difference between the folding energy of the protein complex and the sum of the folding energies of its binding partners. We show that using a pre-trained inverse-folding model as a proxy for folding energy provides strong zero-shot performance, and can be fine-tuned with (1) copious folding energy measurements and (2) more limited binding energy measurements. The resulting predictor, StaB-ddG, is the first deep learning predictor to match the accuracy of the state-of-the-art empirical force-field method FoldX, while offering an over 1,000x speed-up.

q-bio.BM↗

arXiv2025

Large Language Models are Good Relational Learners

Large language models (LLMs) have demonstrated remarkable capabilities across various domains, yet their application to relational deep learning (RDL) remains underexplored. Existing approaches adapt LLMs by traversing relational links between entities in a database and converting the structured data into flat text documents. Still, this text-based serialization disregards critical relational structures, introduces redundancy, and often exceeds standard LLM context lengths. We introduce Rel-LLM, a novel architecture that utilizes a graph neural network (GNN)- based encoder to generate structured relational prompts for LLMs within a retrieval-augmented generation (RAG) framework. Unlike traditional text-based serialization approaches, our method preserves the inherent relational structure of databases while enabling LLMs to effectively process and reason over complex entity relationships. Specifically, the GNN encoder extracts a local subgraph around an entity to build feature representations that contain relevant entity relationships and temporal dependencies. These representations are transformed into structured prompts using a denormalization process, effectively allowing the LLM to reason over relational structures. Through extensive experiments, we demonstrate that Rel-LLM outperforms existing methods on key RDL tasks, offering a scalable and efficient approach to integrating LLMs with structured data sources. Code is available at https://github.com/smiles724/Rel-LLM.

cs.CL↗

arXiv2025

When to Trust Context: Self-Reflective Debates for Context Reliability

Large language models frequently encounter conflicts between their parametric knowledge and contextual input, often resulting in factual inconsistencies or hallucinations. We propose Self-Reflective Debate for Contextual Reliability (SR-DCR), a lightweight framework that integrates token-level self-confidence with an asymmetric multi-agent debate to adjudicate such conflicts. A critic, deprived of context, challenges a defender who argues from the given passage; a judge model evaluates the debate and determines the context's reliability. The final answer is selected by combining the verdict with model confidence. Experiments on the ClashEval benchmark demonstrate that SR-DCR consistently enhances robustness to misleading context while maintaining accuracy on trustworthy inputs, outperforming both classical debate and confidence-only baselines with minimal computational overhead. The code is available at https://github.com/smiles724/Self-Reflective-Debates.

cs.CL↗

arXiv2025

AnchorAttention: Difference-Aware Sparse Attention with Stripe Granularity

Large Language Models (LLMs) with extended context lengths face significant computational challenges during the pre-filling phase, primarily due to the quadratic complexity of self-attention. Existing methods typically employ dynamic pattern matching and block-sparse low-level implementations. However, their reliance on local information for pattern identification fails to capture global contexts, and the coarse granularity of blocks leads to persistent internal sparsity, resulting in suboptimal accuracy and efficiency. To address these limitations, we propose \textbf{AnchorAttention}, a difference-aware, dynamic sparse attention mechanism that efficiently identifies critical attention regions at a finer stripe granularity while adapting to global contextual information, achieving superior speed and accuracy. AnchorAttention comprises three key components: (1) \textbf{Pattern-based Anchor Computation}, leveraging the commonalities present across all inputs to rapidly compute a set of near-maximum scores as the anchor; (2) \textbf{Difference-aware Stripe Sparsity Identification}, performing difference-aware comparisons with the anchor to quickly obtain discrete coordinates of significant regions in a stripe-like sparsity pattern; (3) \textbf{Fine-grained Sparse Computation}, replacing the traditional contiguous KV block loading approach with simultaneous discrete KV position loading to maximize sparsity rates while preserving full hardware computational potential. With its finer-grained sparsity strategy, \textbf{AnchorAttention} achieves higher sparsity rates at the same recall level, significantly reducing computation time. Compared to previous state-of-the-art methods, at a text length of 128k, it achieves a speedup of 1.44$\times$ while maintaining higher recall rates.

cs.LG↗

arXiv2025

LocAgent: Graph-Guided LLM Agents for Code Localization

Code localization--identifying precisely where in a codebase changes need to be made--is a fundamental yet challenging task in software maintenance. Existing approaches struggle to efficiently navigate complex codebases when identifying relevant code sections. The challenge lies in bridging natural language problem descriptions with the appropriate code elements, often requiring reasoning across hierarchical structures and multiple dependencies. We introduce LocAgent, a framework that addresses code localization through graph-based representation. By parsing codebases into directed heterogeneous graphs, LocAgent creates a lightweight representation that captures code structures (files, classes, functions) and their dependencies (imports, invocations, inheritance), enabling LLM agents to effectively search and locate relevant entities through powerful multi-hop reasoning. Experimental results on real-world benchmarks demonstrate that our approach significantly enhances accuracy in code localization. Notably, our method with the fine-tuned Qwen-2.5-Coder-Instruct-32B model achieves comparable results to SOTA proprietary models at greatly reduced cost (approximately 86% reduction), reaching up to 92.7% accuracy on file-level localization while improving downstream GitHub issue resolution success rates by 12% for multiple attempts (Pass@10). Our code is available at https://github.com/gersteinlab/LocAgent.

cs.SE↗

arXiv2025

Electric-field Switching of Interlayer Magnetic Order in a van der Waals Heterobilayer via Spin-potential Coupling

Electric-field switching of magnetic order is of significant physical interest and holds great potential for spintronic applications. However, it has rarely been reported in two-dimensional (2D) van der Waals (vdW) magnets due to the inherently weak interaction between spin order and electric fields. Here we propose a general spin-potential mechanism that significantly enhances the magnetoelectric coupling. As a result, the relative stability of different interlayer magnetic orders in an asymmetric van der Waals heterobilayer can be reversed by external electric fields via spin-potential coupling. Based on this mechanism, we designed a series of 2D vdW all-magnetic heterobilayers, such as CrI3/MnSe2, in which a transition from interlayer ferromagnetic (iFM) to antiferromagnetic (iAFM) order is realized by a feasible electric field around 0.1 V/Å. Our findings not only reveal a novel magnetoelectric coupling mechanism, but also present a practical strategy for achieving pure electric-field-driven magnetic order switching

cond-mat.mtrl-sci↗

arXiv2024

A Survey of Generative AI for de novo Drug Design: New Frontiers in Molecule and Protein Generation

Artificial intelligence (AI)-driven methods can vastly improve the historically costly drug design process, with various generative models already in widespread use. Generative models for de novo drug design, in particular, focus on the creation of novel biological compounds entirely from scratch, representing a promising future direction. Rapid development in the field, combined with the inherent complexity of the drug design process, creates a difficult landscape for new researchers to enter. In this survey, we organize de novo drug design into two overarching themes: small molecule and protein generation. Within each theme, we identify a variety of subtasks and applications, highlighting important datasets, benchmarks, and model architectures and comparing the performance of top models. We take a broad approach to AI-driven drug design, allowing for both micro-level comparisons of various methods within each subtask and macro-level observations across different fields. We discuss parallel challenges and approaches between the two applications and highlight future directions for AI-driven de novo drug design as a whole. An organized repository of all covered sources is available at https://github.com/gersteinlab/GenAI4Drug.

q-bio.BM↗

arXiv2024

Evaluating the Generalization Ability of Quantized LLMs: Benchmark, Analysis, and Toolbox

Large language models (LLMs) have exhibited exciting progress in multiple scenarios, while the huge computational demands hinder their deployments in lots of real-world applications. As an effective means to reduce memory footprint and inference cost, quantization also faces challenges in performance degradation at low bit-widths. Understanding the impact of quantization on LLM capabilities, especially the generalization ability, is crucial. However, the community's main focus remains on the algorithms and models of quantization, with insufficient attention given to whether the quantized models can retain the strong generalization abilities of LLMs. In this work, we fill this gap by providing a comprehensive benchmark suite for this research topic, including an evaluation system, detailed analyses, and a general toolbox. Specifically, based on the dominant pipeline in LLM quantization, we primarily explore the impact of calibration data distribution on the generalization of quantized LLMs and conduct the benchmark using more than 40 datasets within two main scenarios. Based on this benchmark, we conduct extensive experiments with two well-known LLMs (English and Chinese) and four quantization algorithms to investigate this topic in-depth, yielding several counter-intuitive and valuable findings, e.g., models quantized using a calibration set with the same distribution as the test data are not necessarily optimal. Besides, to facilitate future research, we also release a modular-designed toolbox, which decouples the overall pipeline into several separate components, e.g., base LLM module, dataset module, quantizer module, etc. and allows subsequent researchers to easily assemble their methods through a simple configuration. Our benchmark suite is publicly available at https://github.com/TsingmaoAI/MI-optimize

cs.LG↗

arXiv2024

SemiReward: A General Reward Model for Semi-supervised Learning

Semi-supervised learning (SSL) has witnessed great progress with various improvements in the self-training framework with pseudo labeling. The main challenge is how to distinguish high-quality pseudo labels against the confirmation bias. However, existing pseudo-label selection strategies are limited to pre-defined schemes or complex hand-crafted policies specially designed for classification, failing to achieve high-quality labels, fast convergence, and task versatility simultaneously. To these ends, we propose a Semi-supervised Reward framework (SemiReward) that predicts reward scores to evaluate and filter out high-quality pseudo labels, which is pluggable to mainstream SSL methods in wide task types and scenarios. To mitigate confirmation bias, SemiReward is trained online in two stages with a generator model and subsampling strategy. With classification and regression tasks on 13 standard SSL benchmarks across three modalities, extensive experiments verify that SemiReward achieves significant performance gains and faster convergence speeds upon Pseudo Label, FlexMatch, and Free/SoftMatch. Code and models are available at https://github.com/Westlake-AI/SemiReward.

cs.LG↗

arXiv2023

Rethinking Explaining Graph Neural Networks via Non-parametric Subgraph Matching

The success of graph neural networks (GNNs) provokes the question about explainability: ``Which fraction of the input graph is the most determinant of the prediction?'' Particularly, parametric explainers prevail in existing approaches because of their more robust capability to decipher the black-box (i.e., target GNNs). In this paper, based on the observation that graphs typically share some common motif patterns, we propose a novel non-parametric subgraph matching framework, dubbed MatchExplainer, to explore explanatory subgraphs. It couples the target graph with other counterpart instances and identifies the most crucial joint substructure by minimizing the node corresponding-based distance. Moreover, we note that present graph sampling or node-dropping methods usually suffer from the false positive sampling problem. To alleviate this issue, we designed a new augmentation paradigm named MatchDrop. It takes advantage of MatchExplainer to fix the most informative portion of the graph and merely operates graph augmentations on the rest less informative part. Extensive experiments on synthetic and real-world datasets show the effectiveness of our MatchExplainer by outperforming all state-of-the-art parametric baselines with significant margins. Results also demonstrate that MatchDrop is a general scheme to be equipped with GNNs for enhanced performance. The code is available at: https://github.com/smiles724/MatchExplainer.

cs.LG↗

arXiv2023

Pre-training of Equivariant Graph Matching Networks with Conformation Flexibility for Drug Binding

The latest biological findings observe that the traditional motionless 'lock-and-key' theory is not generally applicable because the receptor and ligand are constantly moving. Nonetheless, remarkable changes in associated atomic sites and binding pose can provide vital information in understanding the process of drug binding. Based on this mechanism, molecular dynamics (MD) simulations were invented as a useful tool for investigating the dynamic properties of a molecular system. However, the computational expenditure limits the growth and application of protein trajectory-related studies, thus hindering the possibility of supervised learning. To tackle this obstacle, we present a novel spatial-temporal pre-training method based on the modified Equivariant Graph Matching Networks (EGMN), dubbed ProtMD, which has two specially designed self-supervised learning tasks: an atom-level prompt-based denoising generative task and a conformation-level snapshot ordering task to seize the flexibility information inside MD trajectories with very fine temporal resolutions. The ProtMD can grant the encoder network the capacity to capture the time-dependent geometric mobility of conformations along MD trajectories. Two downstream tasks are chosen, i.e., the binding affinity prediction and the ligand efficacy prediction, to verify the effectiveness of ProtMD through linear detection and task-specific fine-tuning. We observe a huge improvement from current state-of-the-art methods, with a decrease of 4.3% in RMSE for the binding affinity problem and an average increase of 13.8% in AUROC and AUPRC for the ligand efficacy problem. The results demonstrate valuable insight into a strong correlation between the magnitude of conformation's motion in the 3D space (i.e., flexibility) and the strength with which the ligand binds with its receptor.

cs.CE↗

arXiv2023

Improving Molecular Representation Learning with Metric Learning-enhanced Optimal Transport

Training data are usually limited or heterogeneous in many chemical and biological applications. Existing machine learning models for chemistry and materials science fail to consider generalizing beyond training domains. In this article, we develop a novel optimal transport-based algorithm termed MROT to enhance their generalization capability for molecular regression problems. MROT learns a continuous label of the data by measuring a new metric of domain distances and a posterior variance regularization over the transport plan to bridge the chemical domain gap. Among downstream tasks, we consider basic chemical regression tasks in unsupervised and semi-supervised settings, including chemical property prediction and materials adsorption selection. Extensive experiments show that MROT significantly outperforms state-of-the-art models, showing promising potential in accelerating the discovery of new substances with desired properties.

cs.LG↗

arXiv2023

Integration of Pre-trained Protein Language Models into Geometric Deep Learning Networks

Geometric deep learning has recently achieved great success in non-Euclidean domains, and learning on 3D structures of large biomolecules is emerging as a distinct research area. However, its efficacy is largely constrained due to the limited quantity of structural data. Meanwhile, protein language models trained on substantial 1D sequences have shown burgeoning capabilities with scale in a broad range of applications. Several previous studies consider combining these different protein modalities to promote the representation power of geometric neural networks, but fail to present a comprehensive understanding of their benefits. In this work, we integrate the knowledge learned by well-trained protein language models into several state-of-the-art geometric networks and evaluate a variety of protein representation learning benchmarks, including protein-protein interface prediction, model quality assessment, protein-protein rigid-body docking, and binding affinity prediction. Our findings show an overall improvement of 20% over baselines. Strong evidence indicates that the incorporation of protein language models' knowledge enhances geometric networks' capacity by a significant margin and can be generalized to complex tasks.

cs.LG↗

arXiv2023

A Hierarchical Training Paradigm for Antibody Structure-sequence Co-design

Therapeutic antibodies are an essential and rapidly expanding drug modality. The binding specificity between antibodies and antigens is decided by complementarity-determining regions (CDRs) at the tips of these Y-shaped proteins. In this paper, we propose a hierarchical training paradigm (HTP) for the antibody sequence-structure co-design. HTP consists of four levels of training stages, each corresponding to a specific protein modality within a particular protein domain. Through carefully crafted tasks in different stages, HTP seamlessly and effectively integrates geometric graph neural networks (GNNs) with large-scale protein language models to excavate evolutionary information from not only geometric structures but also vast antibody and non-antibody sequence databases, which determines ligand binding pose and strength. Empirical experiments show that HTP sets the new state-of-the-art performance in the co-design problem as well as the fix-backbone design. Our research offers a hopeful path to unleash the potential of deep generative architectures and seeks to illuminate the way forward for the antibody sequence and structure co-design challenge.

q-bio.BM↗

arXiv2023

Architecture-Agnostic Masked Image Modeling -- From ViT back to CNN

Masked image modeling, an emerging self-supervised pre-training method, has shown impressive success across numerous downstream vision tasks with Vision transformers. Its underlying idea is simple: a portion of the input image is masked out and then reconstructed via a pre-text task. However, the working principle behind MIM is not well explained, and previous studies insist that MIM primarily works for the Transformer family but is incompatible with CNNs. In this work, we observe that MIM essentially teaches the model to learn better middle-order interactions among patches for more generalized feature extraction. We then propose an Architecture-Agnostic Masked Image Modeling framework (A$^2$MIM), which is compatible with both Transformers and CNNs in a unified way. Extensive experiments on popular benchmarks show that A$^2$MIM learns better representations without explicit design and endows the backbone model with the stronger capability to transfer to various downstream tasks.

cs.CV↗

arXiv2023

Molformer: Motif-based Transformer on 3D Heterogeneous Molecular Graphs

Procuring expressive molecular representations underpins AI-driven molecule design and scientific discovery. The research mainly focuses on atom-level homogeneous molecular graphs, ignoring the rich information in subgraphs or motifs. However, it has been widely accepted that substructures play a dominant role in identifying and determining molecular properties. To address such issues, we formulate heterogeneous molecular graphs (HMGs), and introduce a novel architecture to exploit both molecular motifs and 3D geometry. Precisely, we extract functional groups as motifs for small molecules and employ reinforcement learning to adaptively select quaternary amino acids as motif candidates for proteins. Then HMGs are constructed with both atom-level and motif-level nodes. To better accommodate those HMGs, we introduce a variant of Transformer named Molformer, which adopts a heterogeneous self-attention layer to distinguish the interactions between multi-level nodes. Besides, it is also coupled with a multi-scale mechanism to capture fine-grained local patterns with increasing contextual scales. An attentive farthest point sampling algorithm is also proposed to obtain the molecular representations. We validate Molformer across a broad range of domains, including quantum chemistry, physiology, and biophysics. Extensive experiments show that Molformer outperforms or achieves the comparable performance of several state-of-the-art baselines. Our work provides a promising way to utilize informative motifs from the perspective of multi-level graph construction.

q-bio.QM↗

arXiv2023

DiffMD: A Geometric Diffusion Model for Molecular Dynamics Simulations

Molecular dynamics (MD) has long been the de facto choice for simulating complex atomistic systems from first principles. Recently deep learning models become a popular way to accelerate MD. Notwithstanding, existing models depend on intermediate variables such as the potential energy or force fields to update atomic positions, which requires additional computations to perform back-propagation. To waive this requirement, we propose a novel model called DiffMD by directly estimating the gradient of the log density of molecular conformations. DiffMD relies on a score-based denoising diffusion generative model that perturbs the molecular structure with a conditional noise depending on atomic accelerations and treats conformations at previous timeframes as the prior distribution for sampling. Another challenge of modeling such a conformation generation process is that a molecule is kinetic instead of static, which no prior works have strictly studied. To solve this challenge, we propose an equivariant geometric Transformer as the score function in the diffusion process to calculate corresponding gradients. It incorporates the directions and velocities of atomic motions via 3D spherical Fourier-Bessel representations. With multiple architectural improvements, we outperform state-of-the-art baselines on MD17 and isomers of C7O2H10 datasets. This work contributes to accelerating material and drug discovery.

cs.CE↗