arXiv subjects

Zhangyang Gao

Publications and source records attributed to Zhangyang Gao.

At least 37 records · Page 2Linked to original sources

arXiv2025

PFMBench: Protein Foundation Model Benchmark

This study investigates the current landscape and future directions of protein foundation model research. While recent advancements have transformed protein science and engineering, the field lacks a comprehensive benchmark for fair evaluation and in-depth understanding. Since ESM-1B, numerous protein foundation models have emerged, each with unique datasets and methodologies. However, evaluations often focus on limited tasks tailored to specific models, hindering insights into broader generalization and limitations. Specifically, researchers struggle to understand the relationships between tasks, assess how well current models perform across them, and determine the criteria in developing new foundation models. To fill this gap, we present PFMBench, a comprehensive benchmark evaluating protein foundation models across 38 tasks spanning 8 key areas of protein science. Through hundreds of experiments on 17 state-of-the-art models across 38 tasks, PFMBench reveals the inherent correlations between tasks, identifies top-performing models, and provides a streamlined evaluation protocol. Code is available at \href{https://github.com/biomap-research/PFMBench}{\textcolor{blue}{GitHub}}.

q-bio.BM↗

arXiv2025

USTEP: Spatio-Temporal Predictive Learning under A Unified View

Spatio-temporal predictive learning plays a crucial role in self-supervised learning, with wide-ranging applications across a diverse range of fields. Previous approaches for temporal modeling fall into two categories: recurrent-based and recurrent-free methods. The former, while meticulously processing frames one by one, neglect short-term spatio-temporal information redundancies, leading to inefficiencies. The latter naively stack frames sequentially, overlooking the inherent temporal dependencies. In this paper, we re-examine the two dominant temporal modeling approaches within the realm of spatio-temporal predictive learning, offering a unified perspective. Building upon this analysis, we introduce USTEP (Unified Spatio-TEmporal Predictive learning), an innovative framework that reconciles the recurrent-based and recurrent-free methods by integrating both micro-temporal and macro-temporal scales. Extensive experiments on a wide range of spatio-temporal predictive learning demonstrate that USTEP achieves significant improvements over existing temporal modeling approaches, thereby establishing it as a robust solution for a wide range of spatio-temporal applications.

cs.CV↗

arXiv2025

G2PDiffusion: Cross-Species Genotype-to-Phenotype Prediction via Evolutionary Diffusion

Understanding how genes influence phenotype across species is a fundamental challenge in genetic engineering, which will facilitate advances in various fields such as crop breeding, conservation biology, and personalized medicine. However, current phenotype prediction models are limited to individual species and expensive phenotype labeling process, making the genotype-to-phenotype prediction a highly domain-dependent and data-scarce problem. To this end, we suggest taking images as morphological proxies, facilitating cross-species generalization through large-scale multimodal pretraining. We propose the first genotype-to-phenotype diffusion model (G2PDiffusion) that generates morphological images from DNA considering two critical evolutionary signals, i.e., multiple sequence alignments (MSA) and environmental contexts. The model contains three novel components: 1) a MSA retrieval engine that identifies conserved and co-evolutionary patterns; 2) an environment-aware MSA conditional encoder that effectively models complex genotype-environment interactions; and 3) an adaptive phenomic alignment module to improve genotype-phenotype consistency. Extensive experiments show that integrating evolutionary signals with environmental context enriches the model's understanding of phenotype variability across species, thereby offering a valuable and promising exploration into advanced AI-assisted genomic analysis.

cs.LG↗

arXiv2025

dyAb: Flow Matching for Flexible Antibody Design with AlphaFold-driven Pre-binding Antigen

The development of therapeutic antibodies heavily relies on accurate predictions of how antigens will interact with antibodies. Existing computational methods in antibody design often overlook crucial conformational changes that antigens undergo during the binding process, significantly impacting the reliability of the resulting antibodies. To bridge this gap, we introduce dyAb, a flexible framework that incorporates AlphaFold2-driven predictions to model pre-binding antigen structures and specifically addresses the dynamic nature of antigen conformation changes. Our dyAb model leverages a unique combination of coarse-grained interface alignment and fine-grained flow matching techniques to simulate the interaction dynamics and structural evolution of the antigen-antibody complex, providing a realistic representation of the binding process. Extensive experiments show that dyAb significantly outperforms existing models in antibody design involving changing antigen conformations. These results highlight dyAb's potential to streamline the design process for therapeutic antibodies, promising more efficient development cycles and improved outcomes in clinical applications.

q-bio.QM↗

arXiv2024

An Empirical Study: Extensive Deep Temporal Point Process

Temporal point process as the stochastic process on continuous domain of time is commonly used to model the asynchronous event sequence featuring with occurrence timestamps. Thanks to the strong expressivity of deep neural networks, they are emerging as a promising choice for capturing the patterns in asynchronous sequences, in the context of temporal point process. In this paper, we first review recent research emphasis and difficulties in modeling asynchronous event sequences with deep temporal point process, which can be concluded into four fields: encoding of history sequence, formulation of conditional intensity function, relational discovery of events and learning approaches for optimization. We introduce most of recently proposed models by dismantling them into the four parts, and conduct experiments by remodularizing the first three parts with the same learning strategy for a fair empirical evaluation. Besides, we extend the history encoders and conditional intensity function family, and propose a Granger causality discovery framework for exploiting the relations among multi-types of events. Because the Granger causality can be represented by the Granger causality graph, discrete graph structure learning in the framework of Variational Inference is employed to reveal latent structures of the graph. Further experiments show that the proposed framework with latent graph discovery can both capture the relations and achieve an improved fitting and predicting performance.

cs.LG↗

arXiv2024

Relation-Aware Equivariant Graph Networks for Epitope-Unknown Antibody Design and Specificity Optimization

Antibodies are Y-shaped proteins that protect the host by binding to specific antigens, and their binding is mainly determined by the Complementary Determining Regions (CDRs) in the antibody. Despite the great progress made in CDR design, existing computational methods still encounter several challenges: 1) poor capability of modeling complex CDRs with long sequences due to insufficient contextual information; 2) conditioned on pre-given antigenic epitopes and their static interaction with the target antibody; 3) neglect of specificity during antibody optimization leads to non-specific antibodies. In this paper, we take into account a variety of node features, edge features, and edge relations to include more contextual and geometric information. We propose a novel Relation-Aware Antibody Design (RAAD) framework, which dynamically models antigen-antibody interactions for co-designing the sequences and structures of antigen-specific CDRs. Furthermore, we propose a new evaluation metric to better measure antibody specificity and develop a contrasting specificity-enhancing constraint to optimize the specificity of antibodies. Extensive experiments have demonstrated the superior capability of RAAD in terms of antibody modeling, generation, and optimization across different CDR types, sequence lengths, pre-training strategies, and input contexts.

q-bio.QM↗

arXiv2024

SimVPv2: Towards Simple yet Powerful Spatiotemporal Predictive Learning

Recent years have witnessed remarkable advances in spatiotemporal predictive learning, with methods incorporating auxiliary inputs, complex neural architectures, and sophisticated training strategies. While SimVP has introduced a simpler, CNN-based baseline for this task, it still relies on heavy Unet-like architectures for spatial and temporal modeling, which still suffers from high complexity and computational overhead. In this paper, we propose SimVPv2, a streamlined model that eliminates the need for Unet architectures and demonstrates that plain stacks of convolutional layers, enhanced with an efficient Gated Spatiotemporal Attention mechanism, can deliver state-of-the-art performance. SimVPv2 not only simplifies the model architecture but also improves both performance and computational efficiency. On the standard Moving MNIST benchmark, SimVPv2 achieves superior performance compared to SimVP, with fewer FLOPs, about half the training time, and 60% faster inference efficiency. Extensive experiments across eight diverse datasets, including real-world tasks such as traffic forecasting and climate prediction, further demonstrate that SimVPv2 offers a powerful yet straightforward solution, achieving robust generalization across various spatiotemporal learning scenarios. We believe the proposed SimVPv2 can serve as a solid baseline to benefit the spatiotemporal predictive learning community.

cs.LG↗

arXiv2024

From Words to Structured Visuals: A Benchmark and Framework for Text-to-Diagram Generation and Editing

We introduce the task of text-to-diagram generation, which focuses on creating structured visual representations directly from textual descriptions. Existing approaches in text-to-image and text-to-code generation lack the logical organization and flexibility needed to produce accurate, editable diagrams, often resulting in outputs that are either unstructured or difficult to modify. To address this gap, we introduce DiagramGenBenchmark, a comprehensive evaluation framework encompassing eight distinct diagram categories, including flowcharts, model architecture diagrams, and mind maps. Additionally, we present DiagramAgent, an innovative framework with four core modules-Plan Agent, Code Agent, Check Agent, and Diagram-to-Code Agent-designed to facilitate both the generation and refinement of complex diagrams. Our extensive experiments, which combine objective metrics with human evaluations, demonstrate that DiagramAgent significantly outperforms existing baseline models in terms of accuracy, structural coherence, and modifiability. This work not only establishes a foundational benchmark for the text-to-diagram generation task but also introduces a powerful toolset to advance research and applications in this emerging area.

cs.DB↗

arXiv2024

MeToken: Uniform Micro-environment Token Boosts Post-Translational Modification Prediction

Post-translational modifications (PTMs) profoundly expand the complexity and functionality of the proteome, regulating protein attributes and interactions that are crucial for biological processes. Accurately predicting PTM sites and their specific types is therefore essential for elucidating protein function and understanding disease mechanisms. Existing computational approaches predominantly focus on protein sequences to predict PTM sites, driven by the recognition of sequence-dependent motifs. However, these approaches often overlook protein structural contexts. In this work, we first compile a large-scale sequence-structure PTM dataset, which serves as the foundation for fair comparison. We introduce the MeToken model, which tokenizes the micro-environment of each amino acid, integrating both sequence and structural information into unified discrete tokens. This model not only captures the typical sequence motifs associated with PTMs but also leverages the spatial arrangements dictated by protein tertiary structures, thus providing a holistic view of the factors influencing PTM sites. Designed to address the long-tail distribution of PTM types, MeToken employs uniform sub-codebooks that ensure even the rarest PTMs are adequately represented and distinguished. We validate the effectiveness and generalizability of MeToken across multiple datasets, demonstrating its superior performance in accurately identifying PTM types. The results underscore the importance of incorporating structural data and highlight MeToken's potential in facilitating accurate and comprehensive PTM predictions, which could significantly impact proteomics research. The code and datasets are available at https://github.com/A4Bio/MeToken.

cs.LG↗

arXiv2024

GATES: Graph Attention Network with Global Expression Fusion for Deciphering Spatial Transcriptome Architectures

Single-cell spatial transcriptomics (ST) offers a unique approach to measuring gene expression profiles and spatial cell locations simultaneously. However, most existing ST methods assume that cells in closer spatial proximity exhibit more similar gene expression patterns. Such assumption typically results in graph structures that prioritize local spatial information while overlooking global patterns, limiting the ability to fully capture the broader structural features of biological tissues. To overcome this limitation, we propose GATES (Graph Attention neTwork with global Expression fuSion), a novel model designed to capture structural details in spatial transcriptomics data. GATES first constructs an expression graph that integrates local and global information by leveraging both spatial proximity and gene expression similarity. The model then employs an autoencoder with adaptive attention to assign proper weights for neighboring nodes, enhancing its capability of feature extraction. By fusing features of both the spatial and expression graphs, GATES effectively balances spatial context with gene expression data. Experimental results across multiple datasets demonstrate that GATES significantly outperforms existing methods in identifying spatial domains, highlighting its potential for analyzing complex biological tissues. Our code can be accessed on GitHub at https://github.com/xiaoxiongtao/GATES.

q-bio.GN↗

arXiv2024

FlexMol: A Flexible Toolkit for Benchmarking Molecular Relational Learning

Molecular relational learning (MRL) is crucial for understanding the interaction behaviors between molecular pairs, a critical aspect of drug discovery and development. However, the large feasible model space of MRL poses significant challenges to benchmarking, and existing MRL frameworks face limitations in flexibility and scope. To address these challenges, avoid repetitive coding efforts, and ensure fair comparison of models, we introduce FlexMol, a comprehensive toolkit designed to facilitate the construction and evaluation of diverse model architectures across various datasets and performance metrics. FlexMol offers a robust suite of preset model components, including 16 drug encoders, 13 protein sequence encoders, 9 protein structure encoders, and 7 interaction layers. With its easy-to-use API and flexibility, FlexMol supports the dynamic construction of over 70, 000 distinct combinations of model architectures. Additionally, we provide detailed benchmark results and code examples to demonstrate FlexMol's effectiveness in simplifying and standardizing MRL model development and comparison.

cs.LG↗

arXiv2024

Boosting the Power of Small Multimodal Reasoning Models to Match Larger Models with Self-Consistency Training

Multimodal reasoning is a challenging task that requires models to reason across multiple modalities to answer questions. Existing approaches have made progress by incorporating language and visual modalities into a two-stage reasoning framework, separating rationale generation from answer inference. However, these approaches often fall short due to the inadequate quality of the generated rationales. In this work, we delve into the importance of rationales in model reasoning. We observe that when rationales are completely accurate, the model's accuracy significantly improves, highlighting the need for high-quality rationale generation. Motivated by this, we propose MC-CoT, a self-consistency training strategy that generates multiple rationales and answers, subsequently selecting the most accurate through a voting process. This approach not only enhances the quality of generated rationales but also leads to more accurate and robust answers. Through extensive experiments, we demonstrate that our approach significantly improves model performance across various benchmarks. Remarkably, we show that even smaller base models, when equipped with our proposed approach, can achieve results comparable to those of larger models, illustrating the potential of our approach in harnessing the power of rationales for improved multimodal reasoning. The code is available at https://github.com/chengtan9907/mc-cot.

cs.AI↗

arXiv2024

Deciphering RNA Secondary Structure Prediction: A Probabilistic K-Rook Matching Perspective

The secondary structure of ribonucleic acid (RNA) is more stable and accessible in the cell than its tertiary structure, making it essential for functional prediction. Although deep learning has shown promising results in this field, current methods suffer from poor generalization and high complexity. In this work, we reformulate the RNA secondary structure prediction as a K-Rook problem, thereby simplifying the prediction process into probabilistic matching within a finite solution space. Building on this innovative perspective, we introduce RFold, a simple yet effective method that learns to predict the most matching K-Rook solution from the given sequence. RFold employs a bi-dimensional optimization strategy that decomposes the probabilistic matching problem into row-wise and column-wise components to reduce the matching complexity, simplifying the solving process while guaranteeing the validity of the output. Extensive experiments demonstrate that RFold achieves competitive performance and about eight times faster inference efficiency than the state-of-the-art approaches. The code and Colab demo are available in (http://github.com/A4Bio/RFold).

q-bio.BM↗

arXiv2024

FoldToken2: Learning compact, invariant and generative protein structure language

The equivalent nature of 3D coordinates has posed long term challenges in protein structure representation learning, alignment, and generation. Can we create a compact and invariant language that equivalently represents protein structures? Towards this goal, we propose FoldToken2 to transfer equivariant structures into discrete tokens, while maintaining the recoverability of the original structures. From FoldToken1 to FoldToken2, we improve three key components: (1) invariant structure encoder, (2) vector-quantized compressor, and (3) equivalent structure decoder. We evaluate FoldToken2 on the protein structure reconstruction task and show that it outperforms previous FoldToken1 by 20\% in TMScore and 81\% in RMSD. FoldToken2 probably be the first method that works well on both single-chain and multi-chain protein structures quantization. We believe that FoldToken2 will inspire further improvement in protein structure representation learning, structure alignment, and structure generation tasks.

q-bio.BM↗

arXiv2024

Peer Review as A Multi-Turn and Long-Context Dialogue with Role-Based Interactions

Large Language Models (LLMs) have demonstrated wide-ranging applications across various fields and have shown significant potential in the academic peer-review process. However, existing applications are primarily limited to static review generation based on submitted papers, which fail to capture the dynamic and iterative nature of real-world peer reviews. In this paper, we reformulate the peer-review process as a multi-turn, long-context dialogue, incorporating distinct roles for authors, reviewers, and decision makers. We construct a comprehensive dataset containing over 26,841 papers with 92,017 reviews collected from multiple sources, including the top-tier conference and prestigious journal. This dataset is meticulously designed to facilitate the applications of LLMs for multi-turn dialogues, effectively simulating the complete peer-review process. Furthermore, we propose a series of metrics to evaluate the performance of LLMs for each role under this reformulated peer-review setting, ensuring fair and comprehensive evaluations. We believe this work provides a promising perspective on enhancing the LLM-driven peer-review process by incorporating dynamic, role-based interactions. It aligns closely with the iterative and interactive nature of real-world academic peer review, offering a robust foundation for future research and development in this area. We open-source the dataset at https://github.com/chengtan9907/ReviewMT.

cs.CL↗

arXiv2024

Retrieval Meets Reasoning: Even High-school Textbook Knowledge Benefits Multimodal Reasoning

Large language models equipped with retrieval-augmented generation (RAG) represent a burgeoning field aimed at enhancing answering capabilities by leveraging external knowledge bases. Although the application of RAG with language-only models has been extensively explored, its adaptation into multimodal vision-language models remains nascent. Going beyond mere answer generation, the primary goal of multimodal RAG is to cultivate the models' ability to reason in response to relevant queries. To this end, we introduce a novel multimodal RAG framework named RMR (Retrieval Meets Reasoning). The RMR framework employs a bi-modal retrieval module to identify the most relevant question-answer pairs, which then serve as scaffolds for the multimodal reasoning process. This training-free approach not only encourages the model to engage deeply with the reasoning processes inherent in the retrieved content but also facilitates the generation of answers that are precise and richly interpretable. Surprisingly, utilizing solely the ScienceQA dataset, collected from elementary and high school science curricula, RMR significantly boosts the performance of various vision-language models across a spectrum of benchmark datasets, including A-OKVQA, MMBench, and SEED. These outcomes highlight the substantial potential of our multimodal retrieval and reasoning mechanism to improve the reasoning capabilities of vision-language models.

cs.CV↗

arXiv2024

A Graph is Worth $K$ Words: Euclideanizing Graph using Pure Transformer

Can we model Non-Euclidean graphs as pure language or even Euclidean vectors while retaining their inherent information? The Non-Euclidean property have posed a long term challenge in graph modeling. Despite recent graph neural networks and graph transformers efforts encoding graphs as Euclidean vectors, recovering the original graph from vectors remains a challenge. In this paper, we introduce GraphsGPT, featuring an Graph2Seq encoder that transforms Non-Euclidean graphs into learnable Graph Words in the Euclidean space, along with a GraphGPT decoder that reconstructs the original graph from Graph Words to ensure information equivalence. We pretrain GraphsGPT on $100$M molecules and yield some interesting findings: (1) The pretrained Graph2Seq excels in graph representation learning, achieving state-of-the-art results on $8/9$ graph classification and regression tasks. (2) The pretrained GraphGPT serves as a strong graph generator, demonstrated by its strong ability to perform both few-shot and conditional graph generation. (3) Graph2Seq+GraphGPT enables effective graph mixup in the Euclidean space, overcoming previously known Non-Euclidean challenges. (4) The edge-centric pretraining framework GraphsGPT demonstrates its efficacy in graph domain tasks, excelling in both representation and generation. Code is available at \href{https://github.com/A4Bio/GraphsGPT}{GitHub}.

cs.LG↗

arXiv2024

UniIF: Unified Molecule Inverse Folding

Molecule inverse folding has been a long-standing challenge in chemistry and biology, with the potential to revolutionize drug discovery and material science. Despite specified models have been proposed for different small- or macro-molecules, few have attempted to unify the learning process, resulting in redundant efforts. Complementary to recent advancements in molecular structure prediction, such as RoseTTAFold All-Atom and AlphaFold3, we propose the unified model UniIF for the inverse folding of all molecules. We do such unification in two levels: 1) Data-Level: We propose a unified block graph data form for all molecules, including the local frame building and geometric feature initialization. 2) Model-Level: We introduce a geometric block attention network, comprising a geometric interaction, interactive attention and virtual long-term dependency modules, to capture the 3D interactions of all molecules. Through comprehensive evaluations across various tasks such as protein design, RNA design, and material design, we demonstrate that our proposed method surpasses state-of-the-art methods on all tasks. UniIF offers a versatile and effective solution for general molecule inverse folding.

cs.AI↗