arXiv subjects

Yizhen Luo

Publications and source records attributed to Yizhen Luo.

14 recordsLinked to original sources

arXiv2026

Co-Generative De Novo Functional Protein Design

De novo functional protein design aims to generate protein sequences that realize specified biochemical functions without relying on evolutionary templates, enabling broad applications in biotechnology and medicine. Existing approaches adopt either direct function-to-sequence mapping or decoupled structure-sequence generation strategies but often fail to achieve functionality and foldability simultaneously. To address this, we propose CodeFP, a Co-generative protein language model for de novo Functional Protein design that simultaneously decodes sequence and structure tokens, thereby enabling superior simultaneous realization of functionality and foldability. CodeFP utilizes functional local structures to enrich functional semantic encodings, overcoming the suboptimal translation of flat encodings into structure tokens, while introducing auxiliary functional supervision to alleviate training ambiguity stemming from the one-to-many structure-to-token mapping. Extensive experiments show that CodeFP consistently achieves average improvements of 6.1% in functional consistency and 3.2% in foldability over the strongest baseline.

q-bio.QM↗

arXiv2026

Structured Scaling of AI Discovery Across Diverse Scientific Domains

Scientific discovery often requires many cycles of proposing, testing, and refining candidate solutions. Language models can increasingly participate in these loops, but simply generating more attempts does not ensure progress: parallel searches may duplicate one another and iterative refinement may become trapped in poor directions. The central challenge is therefore not only to scale AI-driven discovery, but to structure that scaling so that evaluation signals compound over time. Here we introduce SimpleTES (Simple Test-time Evaluation-driven Scaling), a framework that focuses on the structured scaling of AI discovery loops, organizing evaluator queries across independent trajectories, iterative refinement, local candidate selection, and the selective reuse of evaluated histories. Drawing on structural features of scientific communities, SimpleTES uses a single open-source GPT-OSS model to establish new state-of-the-art solutions across 28 open-ended problems in diverse scientific domains ranging from quantum physics and astronomy to biology, AI, and mathematics. These include a 24.5% reduction in quantum circuit compilation overhead, up to 23% lower propulsive cost for deep-space trajectories, a 2.17x faster lasso-path solver, an 8.5% lower-error whole-brain neural-activity predictor, the fastest reported TriMul kernel, and new mathematical constructions beyond prior human or AI records. We further post-train the model for long-horizon discovery by assigning each attempt the final outcome of the trajectory it helped produce. This improves performance on both training and held-out mathematics problems, further advancing the frontier. Together, these results establish structured scaling as a general mechanism for advancing AI scientific discovery.

cs.LG↗

arXiv2026

Reinforced Reasoning for End-to-End Retrosynthetic Planning

Retrosynthetic planning is a fundamental task in organic chemistry, yet remains challenging due to its combinatorial complexity. To address this, conventional approaches typically rely on hybrid frameworks that combine single-step predictions with external search heuristics, inevitably fracturing the logical coherence between local molecular transformations and global planning objectives. To bridge this gap and embed sophisticated strategic foresight directly into the model's chemical reasoning, we introduce ReTriP, an end-to-end generative framework that reformulates retrosynthesis as a direct Chain-of-Thought reasoning task. We establish a path-coherent molecular representation and employ a progressive training curriculum that transitions from reasoning distillation to reinforcement learning with verifiable rewards, effectively aligning stepwise generation with practical route utility. Empirical evaluation on RetroBench demonstrates that ReTriP achieves state-of-the-art performance, exhibiting superior robustness in long-horizon planning compared to hybrid baselines.

cs.AI↗

arXiv2025

SToFM: a Multi-scale Foundation Model for Spatial Transcriptomics

Spatial Transcriptomics (ST) technologies provide biologists with rich insights into single-cell biology by preserving spatial context of cells. Building foundational models for ST can significantly enhance the analysis of vast and complex data sources, unlocking new perspectives on the intricacies of biological tissues. However, modeling ST data is inherently challenging due to the need to extract multi-scale information from tissue slices containing vast numbers of cells. This process requires integrating macro-scale tissue morphology, micro-scale cellular microenvironment, and gene-scale gene expression profile. To address this challenge, we propose SToFM, a multi-scale Spatial Transcriptomics Foundation Model. SToFM first performs multi-scale information extraction on each ST slice, to construct a set of ST sub-slices that aggregate macro-, micro- and gene-scale information. Then an SE(2) Transformer is used to obtain high-quality cell representations from the sub-slices. Additionally, we construct \textbf{SToCorpus-88M}, the largest high-resolution spatial transcriptomics corpus for pretraining. SToFM achieves outstanding performance on a variety of downstream tasks, such as tissue region semantic segmentation and cell type annotation, demonstrating its comprehensive understanding of ST data through capturing and integrating multi-scale information.

q-bio.GN↗

arXiv2025

PharMolixFM: All-Atom Foundation Models for Molecular Modeling and Generation

Structural biology relies on accurate three-dimensional biomolecular structures to advance our understanding of biological functions, disease mechanisms, and therapeutics. While recent advances in deep learning have enabled the development of all-atom foundation models for molecular modeling and generation, existing approaches face challenges in generalization due to the multi-modal nature of atomic data and the lack of comprehensive analysis of training and sampling strategies. To address these limitations, we propose PharMolixFM, a unified framework for constructing all-atom foundation models based on multi-modal generative techniques. Our framework includes three variants using state-of-the-art multi-modal generative models. By formulating molecular tasks as a generalized denoising process with task-specific priors, PharMolixFM achieves robust performance across various structural biology applications. Experimental results demonstrate that PharMolixFM-Diff achieves competitive prediction accuracy in protein-small-molecule docking (83.9% vs. 90.2% RMSD < 2{\AA}, given pocket) with significantly improved inference speed. Moreover, we explore the empirical inference scaling law by introducing more sampling repeats or steps. Our code and model are available at https://github.com/PharMolix/OpenBioMed.

q-bio.BM↗

arXiv2024

MutaPLM: Protein Language Modeling for Mutation Explanation and Engineering

Studying protein mutations within amino acid sequences holds tremendous significance in life sciences. Protein language models (PLMs) have demonstrated strong capabilities in broad biological applications. However, due to architectural design and lack of supervision, PLMs model mutations implicitly with evolutionary plausibility, which is not satisfactory to serve as explainable and engineerable tools in real-world studies. To address these issues, we present MutaPLM, a unified framework for interpreting and navigating protein mutations with protein language models. MutaPLM introduces a protein delta network that captures explicit protein mutation representations within a unified feature space, and a transfer learning pipeline with a chain-of-thought (CoT) strategy to harvest protein mutation knowledge from biomedical texts. We also construct MutaDescribe, the first large-scale protein mutation dataset with rich textual annotations, which provides cross-modal supervision signals. Through comprehensive experiments, we demonstrate that MutaPLM excels at providing human-understandable explanations for mutational effects and prioritizing novel mutations with desirable properties. Our code, model, and data are open-sourced at https://github.com/PharMolix/MutaPLM.

cs.LG↗

arXiv2024

Learning Multi-view Molecular Representations with Structured and Unstructured Knowledge

Capturing molecular knowledge with representation learning approaches holds significant potential in vast scientific fields such as chemistry and life science. An effective and generalizable molecular representation is expected to capture the consensus and complementary molecular expertise from diverse views and perspectives. However, existing works fall short in learning multi-view molecular representations, due to challenges in explicitly incorporating view information and handling molecular knowledge from heterogeneous sources. To address these issues, we present MV-Mol, a molecular representation learning model that harvests multi-view molecular expertise from chemical structures, unstructured knowledge from biomedical texts, and structured knowledge from knowledge graphs. We utilize text prompts to model view information and design a fusion architecture to extract view-based molecular representations. We develop a two-stage pre-training procedure, exploiting heterogeneous data of varying quality and quantity. Through extensive experiments, we show that MV-Mol provides improved representations that substantially benefit molecular property prediction. Additionally, MV-Mol exhibits state-of-the-art performance in multi-modal comprehension of molecular structures and texts. Code and data are available at https://github.com/PharMolix/OpenBioMed.

cs.LG↗

arXiv2024

LangCell: Language-Cell Pre-training for Cell Identity Understanding

Cell identity encompasses various semantic aspects of a cell, including cell type, pathway information, disease information, and more, which are essential for biologists to gain insights into its biological characteristics. Understanding cell identity from the transcriptomic data, such as annotating cell types, has become an important task in bioinformatics. As these semantic aspects are determined by human experts, it is impossible for AI models to effectively carry out cell identity understanding tasks without the supervision signals provided by single-cell and label pairs. The single-cell pre-trained language models (PLMs) currently used for this task are trained only on a single modality, transcriptomics data, lack an understanding of cell identity knowledge. As a result, they have to be fine-tuned for downstream tasks and struggle when lacking labeled data with the desired semantic labels. To address this issue, we propose an innovative solution by constructing a unified representation of single-cell data and natural language during the pre-training phase, allowing the model to directly incorporate insights related to cell identity. More specifically, we introduce $\textbf{LangCell}$, the first $\textbf{Lang}$uage-$\textbf{Cell}$ pre-training framework. LangCell utilizes texts enriched with cell identity information to gain a profound comprehension of cross-modal knowledge. Results from experiments conducted on different benchmarks show that LangCell is the only single-cell PLM that can work effectively in zero-shot cell identity understanding scenarios, and also significantly outperforms existing models in few-shot and fine-tuning cell identity understanding scenarios.

q-bio.GN↗

arXiv2024

DeepCRE: Transforming Drug R&D via AI-Driven Cross-drug Response Evaluation

The fields of therapeutic application and drug research and development (R&D) both face substantial challenges, i.e., the therapeutic domain calls for more treatment alternatives, while numerous promising pre-clinical drugs have failed in clinical trials. One of the reasons is the inadequacy of Cross-drug Response Evaluation (CRE) during the late stages of drug R&D. Although in-silico CRE models bring a promising solution, existing methodologies are restricted to early stages of drug R&D, such as target and cell-line levels, offering limited improvement to clinical success rates. Herein, we introduce DeepCRE, a pioneering AI model designed to predict CRE effectively in the late stages of drug R&D. DeepCRE outperforms the existing best models by achieving an average performance improvement of 17.7% in patient-level CRE, and a 5-fold increase in indication-level CRE, facilitating more accurate personalized treatment predictions and better pharmaceutical value assessment for indications, respectively. Furthermore, DeepCRE has identified a set of six drug candidates that show significantly greater effectiveness than a comparator set of two approved drugs in 5/8 colorectal cancer organoids. This demonstrates the capability of DeepCRE to systematically uncover a spectrum of drug candidates with enhanced therapeutic effects, highlighting its potential to transform drug R&D.

cs.AI↗

arXiv2023

Towards Unified AI Drug Discovery with Multiple Knowledge Modalities

In recent years, AI models that mine intrinsic patterns from molecular structures and protein sequences have shown promise in accelerating drug discovery. However, these methods partly lag behind real-world pharmaceutical approaches of human experts that additionally grasp structured knowledge from knowledge bases and unstructured knowledge from biomedical literature. To bridge this gap, we propose KEDD, a unified, end-to-end, and multimodal deep learning framework that optimally incorporates both structured and unstructured knowledge for vast AI drug discovery tasks. The framework first extracts underlying characteristics from heterogeneous inputs, and then applies multimodal fusion for accurate prediction. To mitigate the problem of missing modalities, we leverage multi-head sparse attention and a modality masking mechanism to extract relevant information robustly. Benefiting from integrated knowledge, our framework achieves a deeper understanding of molecule entities, brings significant improvements over state-of-the-art methods on a wide range of tasks and benchmarks, and reveals its promising potential in assisting real-world drug discovery.

cs.LG↗

arXiv2023

BioMedGPT: Open Multimodal Generative Pre-trained Transformer for BioMedicine

Foundation models (FMs) have exhibited remarkable performance across a wide range of downstream tasks in many domains. Nevertheless, general-purpose FMs often face challenges when confronted with domain-specific problems, due to their limited access to the proprietary training data in a particular domain. In biomedicine, there are various biological modalities, such as molecules, proteins, and cells, which are encoded by the language of life and exhibit significant modality gaps with human natural language. In this paper, we introduce BioMedGPT, an open multimodal generative pre-trained transformer (GPT) for biomedicine, to bridge the gap between the language of life and human natural language. BioMedGPT allows users to easily ``communicate'' with diverse biological modalities through free text, which is the first of its kind. BioMedGPT aligns different biological modalities with natural language via a large generative language model, namely, BioMedGPT-LM. We publish BioMedGPT-10B, which unifies the feature spaces of molecules, proteins, and natural language via encoding and alignment. Through fine-tuning, BioMedGPT-10B outperforms or is on par with human and significantly larger general-purpose foundation models on the biomedical QA task. It also demonstrates promising performance in the molecule QA and protein QA tasks, which could greatly accelerate the discovery of new drugs and therapeutic targets. In addition, BioMedGPT-LM-7B is the first large generative language model based on Llama2 in the biomedical domain, therefore is commercial friendly. Both BioMedGPT-10B and BioMedGPT-LM-7B are open-sourced to the research community. In addition, we publish the datasets that are meticulously curated for the alignment of multi-modalities, i.e., PubChemQA and UniProtQA. All the models, codes, and datasets are available at \url{https://github.com/PharMolix/OpenBioMed}.

cs.CE↗

arXiv2023

MolFM: A Multimodal Molecular Foundation Model

Molecular knowledge resides within three different modalities of information sources: molecular structures, biomedical documents, and knowledge bases. Effective incorporation of molecular knowledge from these modalities holds paramount significance in facilitating biomedical research. However, existing multimodal molecular foundation models exhibit limitations in capturing intricate connections between molecular structures and texts, and more importantly, none of them attempt to leverage a wealth of molecular expertise derived from knowledge graphs. In this study, we introduce MolFM, a multimodal molecular foundation model designed to facilitate joint representation learning from molecular structures, biomedical texts, and knowledge graphs. We propose cross-modal attention between atoms of molecular structures, neighbors of molecule entities and semantically related texts to facilitate cross-modal comprehension. We provide theoretical analysis that our cross-modal pre-training captures local and global molecular knowledge by minimizing the distance in the feature space between different modalities of the same molecule, as well as molecules sharing similar structures or functions. MolFM achieves state-of-the-art performance on various downstream tasks. On cross-modal retrieval, MolFM outperforms existing models with 12.13% and 5.04% absolute gains under the zero-shot and fine-tuning settings, respectively. Furthermore, qualitative analysis showcases MolFM's implicit ability to provide grounding from molecular substructures and knowledge graphs. Code and models are available on https://github.com/BioFM/OpenBioMed.

q-bio.BM↗

arXiv2023

CogDL: A Comprehensive Library for Graph Deep Learning

Graph neural networks (GNNs) have attracted tremendous attention from the graph learning community in recent years. It has been widely adopted in various real-world applications from diverse domains, such as social networks and biological graphs. The research and applications of graph deep learning present new challenges, including the sparse nature of graph data, complicated training of GNNs, and non-standard evaluation of graph tasks. To tackle the issues, we present CogDL, a comprehensive library for graph deep learning that allows researchers and practitioners to conduct experiments, compare methods, and build applications with ease and efficiency. In CogDL, we propose a unified design for the training and evaluation of GNN models for various graph tasks, making it unique among existing graph learning libraries. By utilizing this unified trainer, CogDL can optimize the GNN training loop with several training techniques, such as mixed precision training. Moreover, we develop efficient sparse operators for CogDL, enabling it to become the most competitive graph library for efficiency. Another important CogDL feature is its focus on ease of use with the aim of facilitating open and reproducible research of graph learning. We leverage CogDL to report and maintain benchmark results on fundamental graph tasks, which can be reproduced and directly used by the community.

cs.SI↗

arXiv2022

DAIR-V2X: A Large-Scale Dataset for Vehicle-Infrastructure Cooperative 3D Object Detection

Autonomous driving faces great safety challenges for a lack of global perspective and the limitation of long-range perception capabilities. It has been widely agreed that vehicle-infrastructure cooperation is required to achieve Level 5 autonomy. However, there is still NO dataset from real scenarios available for computer vision researchers to work on vehicle-infrastructure cooperation-related problems. To accelerate computer vision research and innovation for Vehicle-Infrastructure Cooperative Autonomous Driving (VICAD), we release DAIR-V2X Dataset, which is the first large-scale, multi-modality, multi-view dataset from real scenarios for VICAD. DAIR-V2X comprises 71254 LiDAR frames and 71254 Camera frames, and all frames are captured from real scenes with 3D annotations. The Vehicle-Infrastructure Cooperative 3D Object Detection problem (VIC3D) is introduced, formulating the problem of collaboratively locating and identifying 3D objects using sensory inputs from both vehicle and infrastructure. In addition to solving traditional 3D object detection problems, the solution of VIC3D needs to consider the temporal asynchrony problem between vehicle and infrastructure sensors and the data transmission cost between them. Furthermore, we propose Time Compensation Late Fusion (TCLF), a late fusion framework for the VIC3D task as a benchmark based on DAIR-V2X. Find data, code, and more up-to-date information at https://thudair.baai.ac.cn/index and https://github.com/AIR-THU/DAIR-V2X.

cs.CV↗