Yan Cui

Wuque Cai, Hongze Sun, Rui Liu et al.

Spiking neural networks (SNNs) mimic brain computational strategies, and exhibit substantial capabilities in spatiotemporal information processing. As an essential factor for human perception, visual attention refers to the dynamic process for selecting salient regions in biological vision systems. Although visual attention mechanisms have achieved great success in computer vision applications, they are rarely introduced into SNNs. Inspired by experimental observations on predictive attentional remapping, we propose a new spatial-channel-temporal-fused attention (SCTFA) module that can guide SNNs to efficiently capture underlying target regions by utilizing accumulated historical spatial-channel information in the present study. Through a systematic evaluation on three event stream datasets (DVS Gesture, SL-Animals-DVS and MNIST-DVS), we demonstrate that the SNN with the SCTFA module (SCTFA-SNN) not only significantly outperforms the baseline SNN (BL-SNN) and two other SNN models with degenerated attention modules, but also achieves competitive accuracy with existing state-of-the-art methods. Additionally, our detailed analysis shows that the proposed SCTFA-SNN model has strong robustness to noise and outstanding stability when faced with incomplete data, while maintaining acceptable complexity and efficiency. Overall, these findings indicate that incorporating appropriate cognitive mechanisms of the brain may provide a promising approach to elevate the capabilities of SNNs.

Hongze Sun, Wuque Cai, Baoxin Yang et al.

Spiking neural networks (SNNs) have demonstrated excellent capabilities in various intelligent scenarios. Most existing methods for training SNNs are based on the concept of synaptic plasticity; however, learning in the realistic brain also utilizes intrinsic non-synaptic mechanisms of neurons. The spike threshold of biological neurons is a critical intrinsic neuronal feature that exhibits rich dynamics on a millisecond timescale and has been proposed as an underlying mechanism that facilitates neural information processing. In this study, we develop a novel synergistic learning approach that involves simultaneously training synaptic weights and spike thresholds in SNNs. SNNs trained with synapse-threshold synergistic learning~(STL-SNNs) achieve significantly superior performance on various static and neuromorphic datasets than SNNs trained with two degenerated single-learning models. During training, the synergistic learning approach optimizes neural thresholds, providing the network with stable signal transmission via appropriate firing rates. Further analysis indicates that STL-SNNs are robust to noisy data and exhibit low energy consumption for deep network structures. Additionally, the performance of STL-SNN can be further improved by introducing a generalized joint decision framework. Overall, our findings indicate that biologically plausible synergies between synaptic and intrinsic non-synaptic mechanisms may provide a promising approach for developing highly efficient SNN learning methods.

Yan Cui, Jacob S. Leiby, Wenhui Lei et al.

Integrating molecular, morphological, and clinical data is essential for basic and translational biomedical research, yet systematic frameworks for jointly modeling these modalities remain limited. Here we present Haiku, a tri-modal contrastive learning model trained on multiplexed immunofluorescence (mIF). It comprises 26.7 million spatial proteomics patches from 3,218 tissue sections across 1,606 patients spanning 11 organ types, with matched hematoxylin and eosin (H&E) histology and clinical metadata aligned in a shared embedding space. Haiku enables three-way cross-modal retrieval, improves downstream classification and clinical prediction tasks over unimodal baselines, and supports zero-shot biomarker inference through fusion retrieval conditioned on clinical metadata-only text descriptions. Across tasks, Haiku outperforms competing approaches, achieving cross-modal retrieval (Recall@50 up to 0.611 versus near-zero baseline), survival prediction (C-index 0.737, +7.91% relative improvement), and zero-shot biomarker inference (mean Pearson correlation 0.718 across 52 biomarkers). Furthermore, we introduce a counterfactual prediction framework in which modifying only clinical metadata while fixing tissue morphology surfaces niche-specific molecular shifts associated with breast cancer stage progression and lung cancer survival outcomes. In a lung adenocarcinoma case study, the counterfactual analysis recovers niche-specific shifts characterized by increased CD8 and granzyme B, reduced PD-L1, and decreased Ki67, broadly consistent with patterns reported for favorable outcomes. We present these counterfactual results as exploratory, hypothesis-generating signals rather than mechanistic claims. These capabilities demonstrate that tri-modal alignment via Haiku enables integrative analysis of spatial biology, bridging molecular measurements with clinical context for biological exploration.

Xiangru Tang, Zhuoyun Yu, Jiapeng Chen et al.

Virtual cell modeling represents an emerging frontier at the intersection of artificial intelligence and biology, aiming to predict quantities such as responses to diverse perturbations quantitatively. However, autonomously building computational models for virtual cells is challenging due to the complexity of biological systems, the heterogeneity of data modalities, and the need for domain-specific expertise across multiple disciplines. Here, we introduce CellForge, an agentic system that leverages a multi-agent framework that transforms presented biological datasets and research objectives directly into optimized computational models for virtual cells. More specifically, given only raw single-cell multi-omics data and task descriptions as input, CellForge outputs both an optimized model architecture and executable code for training virtual cell models and inference. The framework integrates three core modules: Task Analysis for presented dataset characterization and relevant literature retrieval, Method Design, where specialized agents collaboratively develop optimized modeling strategies, and Experiment Execution for automated generation of code. The agents in the Design module are separated into experts with differing perspectives and a central moderator, and have to collaboratively exchange solutions until they achieve a reasonable consensus. We demonstrate CellForge's capabilities in single-cell perturbation prediction, using six diverse datasets that encompass gene knockouts, drug treatments, and cytokine stimulations across multiple modalities. CellForge consistently outperforms task-specific state-of-the-art methods. Overall, CellForge demonstrates how iterative interaction between LLM agents with differing perspectives provides better solutions than directly addressing a modeling challenge. Our code is publicly available at https://github.com/gersteinlab/CellForge.

Chen-Chen Zong, Yu-Qi Chi, Xie-Yang Wang et al.

Open-set active learning (OSAL) aims to identify informative samples for annotation when unlabeled data may contain previously unseen classes-a common challenge in safety-critical and open-world scenarios. Existing approaches typically rely on separately trained open-set detectors, introducing substantial training overhead and overlooking the supervisory value of labeled unknowns for improving known-class learning. In this paper, we propose E$^2$OAL (Effective and Efficient Open-set Active Learning), a unified and detector-free framework that fully exploits labeled unknowns for both stronger supervision and more reliable querying. E$^2$OAL first uncovers the latent class structure of unknowns through label-guided clustering in a frozen contrastively pre-trained feature space, optimized by a structure-aware F1-product objective. To leverage labeled unknowns, it employs a Dirichlet-calibrated auxiliary head that jointly models known and unknown categories, improving both confidence calibration and known-class discrimination. Building on this, a logit-margin purity score estimates the likelihood of known classes to construct a high-purity candidate pool, while an OSAL-specific informativeness metric prioritizes partially ambiguous yet reliable samples. These components together form a flexible two-stage query strategy with adaptive precision control and minimal hyperparameter sensitivity. Extensive experiments across multiple OSAL benchmarks demonstrate that E$^2$OAL consistently surpasses state-of-the-art methods in accuracy, efficiency, and query precision, highlighting its effectiveness and practicality for real-world applications. The code is available at github.com/chenchenzong/E2OAL.

Songhao Li, Jonathan Xu, Tiancheng Bao et al.

Agentic AI is rapidly advancing in healthcare and biomedical research. However, in medical image analysis, their performance and adoption remain limited due to the lack of a robust ecosystem, insufficient toolsets, and the absence of real-time interactive expert feedback. Here we present "TissueLab", a co-evolving agentic AI system that allows researchers to ask direct questions, automatically plan and generate explainable workflows, and conduct real-time analyses where experts can visualize intermediate results and refine them. TissueLab integrates tool factories across pathology, radiology, and spatial omics domains. By standardizing inputs, outputs, and capabilities of diverse tools, the system determines when and how to invoke them to address research and clinical questions. Across diverse tasks with clinically meaningful quantifications that inform staging, prognosis, and treatment planning, TissueLab achieves state-of-the-art performance compared with end-to-end vision-language models (VLMs) and other agentic AI systems such as GPT-5. Moreover, TissueLab continuously learns from clinicians, evolving toward improved classifiers and more effective decision strategies. With active learning, it delivers accurate results in unseen disease contexts within minutes, without requiring massive datasets or prolonged retraining. Released as a sustainable open-source ecosystem, TissueLab aims to accelerate computational research and translational adoption in medical imaging while establishing a foundation for the next generation of medical AI.

Linxin Song, Yan Cui, Ao Luo et al.

Transformer-based models excel in various natural language processing (NLP) tasks, attracting countless efforts to explain their inner workings. Prior methods explain Transformers by focusing on the raw gradient and attention as token attribution scores, where non-relevant information is often considered during explanation computation, resulting in confusing results. In this work, we propose highlighting the important information and eliminating irrelevant information by a refined information flow on top of the layer-wise relevance propagation (LRP) method. Specifically, we consider identifying syntactic and positional heads as important attention heads and focus on the relevance obtained from these important heads. Experimental results demonstrate that irrelevant information does distort output attribution scores and then should be masked during explanation computation. Compared to eight baselines on both classification and question-answering datasets, our method consistently outperforms with over 3\% to 33\% improvement on explanation metrics, providing superior explanation performance. Our anonymous code repository is available at: https://github.com/LinxinS97/Mask-LRP

Zhijiang Tang, Jiaxin Qi, Yan Cui et al.

DNA sequence encoding is fundamental to gene function prediction, protein synthesis, and diverse downstream biological tasks. Despite the substantial progress achieved by large-scale DNA sequence pretraining, existing studies have overwhelmingly emphasized pretraining scale and custom downstream evaluation datasets, while neglecting some essential components of the pretraining paradigm. In this paper, we reveal three critical yet heretofore overlooked problems in DNA pretraining: inappropriate downstream datasets, inherent flaws in the neighbor-masking strategy, and the lack of detailed discussion on vocabulary. Therefore, we undertake comprehensive investigations and propose principled guidelines, including selection criteria for evaluation datasets, guiding task design, and in-depth vocabulary analysis. Extensive experiments validate the significance of our identified problems and support the rationale behind our recommendations. Finally, we introduce a standardized testbed that enables reproducible and rigorous benchmarking of DNA pretraining methods to advance the development of genomic foundation models.

Jiaxin Qi, Hang Li, Yan Cui et al.

Gene Regulatory Network (GRN) inference is essential for understanding complex cellular mechanisms, rendered tractable through single-cell transcriptomic data. With the emergence of single-cell Foundation Models (scFMs), enhanced transcriptomic encoding is widely expected to revolutionize GRN inference. However, we observe that their performance remains far from satisfactory. The primary reason is that the standard reconstruction-based pre-training objectives often fail to explicitly capture latent regulatory signals. To bridge this gap, we first introduce a GRN generalization benchmark designed to evaluate regulatory predictions on unseen genes and datasets, which relies on the zero-shot capabilities of scFMs and is inherently challenging for traditional methods. Furthermore, to unlock the regulatory knowledge within the foundation models, we propose two novel methods, Virtual Value Perturbation and Gradient Trajectory, to distill implicit regulatory information from scFMs into highly generalizable inter-gene features. Extensive experiments demonstrate that our approach significantly outperforms existing methods, establishing a new paradigm for leveraging the potential of scFMs in universal GRN inference.

Jiaxin Qi, Yan Cui, Jianqiang Huang et al.

Classes, as fundamental elements of Computer Vision, have been extensively studied within incremental learning frameworks. In contrast, tokens, which play essential roles in many research fields, exhibit similar characteristics of growth, yet investigations into their incremental learning remain significantly scarce. This research gap primarily stems from the holistic nature of tokens in language, which imposes significant challenges on the design of incremental learning frameworks for them. To overcome this obstacle, in this work, we turn to a type of token, gene, for a large-scale biological dataset--single-cell transcriptomics--to formulate a pipeline for gene incremental learning and establish corresponding evaluations. We found that the forgetting problem also exists in gene incremental learning, thus we adapted existing class incremental learning methods to mitigate the forgetting of genes. Through extensive experiments, we demonstrated the soundness of our framework design and evaluations, as well as the effectiveness of our method adaptations. Finally, we provide a complete benchmark for gene incremental learning in single-cell transcriptomics.

Bangsheng Tang, Carl Chengyan Fu, Fei Kou et al.

Speculative decoding is a standard method for accelerating the inference speed of large language models. However, scaling it for production environments poses several engineering challenges, including efficiently implementing different operations (e.g., tree attention and multi-round speculative decoding) on GPU. In this paper, we detail the training and inference optimization techniques that we have implemented to enable EAGLE-based speculative decoding at a production scale for Llama models. With these changes, we achieve a new state-of-the-art inference latency for Llama models. For example, Llama4 Maverick decodes at a speed of about 4 ms per token (with a batch size of one) on 8 NVIDIA H100 GPUs, which is 10% faster than the previously best known method. Furthermore, for EAGLE-based speculative decoding, our optimizations enable us to achieve a speed-up for large batch sizes between 1.4x and 2.0x at production scale.

Yan Cui, Shuhong Liu, Liuzhuozheng Li et al.

In modern machine learning, the trend of harnessing self-supervised learning to derive high-quality representations without label dependency has garnered significant attention. However, the absence of label information, coupled with the inherently high-dimensional nature, improves the difficulty for the interpretation of learned representations. Consequently, indirect evaluations become the popular metric for evaluating the quality of these features, leading to a biased validation of the learned representation rationale. To address these challenges, we introduce a novel approach termed Concept-based Explainable Image Representation (CEIR). Initially, using the Concept-based Model (CBM) incorporated with pretrained CLIP and concepts generated by GPT-4, we project input images into a concept vector space. Subsequently, a Variational Autoencoder (VAE) learns the latent representation from these projected concepts, which serves as the final image representation. Due to the capability of the representation to encapsulate high-level, semantically relevant concepts, the model allows for attributions to a human-comprehensible concept space. This not only enhances interpretability but also preserves the robustness essential for downstream tasks. For instance, our method exhibits state-of-the-art unsupervised clustering performance on benchmarks such as CIFAR10, CIFAR100, and STL10. Furthermore, capitalizing on the universality of human conceptual understanding, CEIR can seamlessly extract the related concept from open-world images without fine-tuning. This offers a fresh approach to automatic label generation and label manipulation.

Yinuo Xu, Yan Cui, Mingyao Li et al.

Identifying cell types and subtypes in routine histopathology is fundamental for understanding disease. Existing tile-based models capture nuclear detail but miss the broader tissue context that influences cell identity. Current human annotations are coarse-grained and uneven across studies, making fine-grained, subtype-level classification difficult. In this study, we build a marker-guided dataset from Xenium spatial transcriptomics with single-cell resolution labels for more than two million cells across eight organs and 16 classes to address the lack of high-quality annotations. Leveraging this data resource, we introduce NuClass, a pathologist workflow inspired framework for cell-wise multi-scale integration of nuclear morphology and microenvironmental context. It combines Path local, which focuses on nuclear morphology from 224x224 pixel crops, and Path global, which models the surrounding 1024x1024 pixel neighborhood, through a learnable gating module that balances local and global information. An uncertainty-guided objective directs the global path to prioritize regions where the local path is uncertain, and we provide calibrated confidence estimates and Grad-CAM maps for interpretability. Evaluated on three fully held-out cohorts, NuClass achieves up to 96 percent F1 for its best-performing class, outperforming strong baselines. Our results demonstrate that multi-scale, uncertainty-aware fusion can bridge the gap between slide-level pathological foundation models and reliable, cell-level phenotype prediction.

Pengze Xue, Shanwen Wang, Fei Zhou et al.

Image deraining is an essential vision technique that removes rain streaks and water droplets, enhancing clarity for critical vision tasks like autonomous driving. However, current single-scale models struggle with fine-grained recovery and global consistency. To address this challenge, we propose Progressive Rain removal with Integrated State-space Modeling (PRISM), a progressive three-stage framework: Coarse Extraction Network (CENet), Frequency Fusion Network (SFNet), and Refine Network (RNet). Specifically, CENet and SFNet utilize a novel Hybrid Attention UNet (HA-UNet) for multi-scale feature aggregation by combining channel attention with windowed spatial transformers. Moreover, we propose Hybrid Domain Mamba (HDMamba) for SFNet to jointly model spatial semantics and wavelet domain characteristics. Finally, RNet recovers the fine-grained structures via an original-resolution subnetwork. Our model learns high-frequency rain characteristics while preserving structural details and maintaining global context, leading to improved image quality. Our method achieves competitive results on multiple datasets against recent deraining methods.

Hongze Sun, Wuque Cai, Duo Chen et al.

As a foundational architecture of artificial intelligence models, Transformer has been recently adapted to spiking neural networks with promising performance across various tasks. However, existing spiking Transformer~(ST)-based models require a substantial number of parameters and incur high computational costs, thus limiting their deployment in resource-constrained environments. To address these challenges, we propose combining synapse pruning with a synergistic learning-based compensation strategy to derive lightweight ST-based models. Specifically, two types of tailored pruning strategies are introduced to reduce redundancy in the weight matrices of ST blocks: an unstructured $\mathrm{L_{1}P}$ method to induce sparse representations, and a structured DSP method to induce low-rank representations. In addition, we propose an enhanced spiking neuron model, termed the synergistic leaky integrate-and-fire (sLIF) neuron, to effectively compensate for model pruning through synergistic learning between synaptic and intrinsic plasticity mechanisms. Extensive experiments on benchmark datasets demonstrate that the proposed methods significantly reduce model size and computational overhead while maintaining competitive performance. These results validate the effectiveness of the proposed pruning and compensation strategies in constructing efficient and high-performing ST-based models.

Jiaxin Qi, Yan Cui, Jinli Ou et al.

Graph Neural Networks (GNNs) and Transformers share significant similarities in their encoding strategies for interacting with features from nodes of interest, where Transformers use query-key scores and GNNs use edges. Compared to GNNs, which are unable to encode relative positions, Transformers leverage dynamic attention capabilities to better represent relative relationships, thereby becoming the standard backbones in large-scale sequential pre-training. However, the subtle difference prompts us to consider: if positions are no longer crucial, could we substitute Transformers with Graph Neural Networks in some fields such as Single-Cell Transcriptomics? In this paper, we first explore the similarities and differences between GNNs and Transformers, specifically in terms of relative positions. Additionally, we design a synthetic example to illustrate their equivalence where there are no relative positions between tokens in the sample. Finally, we conduct extensive experiments on a large-scale position-agnostic dataset-single-cell transcriptomics-finding that GNNs achieve competitive performance compared to Transformers while consuming fewer computation resources. These findings provide novel insights for researchers in the field of single-cell transcriptomics, challenging the prevailing notion that the Transformer is always the optimum choice.

Hongze Sun, Jun Wang, Wuque Cai et al.

Spiking Neural Networks (SNNs) have emerged as a promising tool for event-based optical flow estimation tasks due to their ability to leverage spatio-temporal information and low-power capabilities. However, the performance of SNN models is often constrained, limiting their application in real-world scenarios. In this work, we address this gap by proposing a novel neural network architecture, ST-FlowNet, specifically tailored for optical flow estimation from event-based data. The ST-FlowNet architecture integrates ConvGRU modules to facilitate cross-modal feature augmentation and temporal alignment of the predicted optical flow, improving the network's ability to capture complex motion dynamics. Additionally, to overcome the challenges associated with training SNNs, we introduce a novel approach to derive SNN models from pre-trained artificial neural networks (ANNs) through ANN-to-SNN conversion or our proposed BISNN method. Notably, the BISNN method alleviates the complexities involved in biological parameter selection, further enhancing the robustness of SNNs in optical flow estimation tasks. Extensive evaluations on three benchmark event-based datasets demonstrate that the SNN-based ST-FlowNet model outperforms state-of-the-art methods, delivering superior performance in accurate optical flow estimation across a diverse range of dynamic visual scenes. Furthermore, the inherent energy efficiency of SNN models is highlighted, establishing a compelling advantage for their practical deployment. Overall, our work presents a novel framework for optical flow estimation using SNNs and event-based data, contributing to the advancement of neuromorphic vision applications.

Xin Yang, Qingling Chang, Xinlin Liu et al.

Monocular depth estimation is the base task in computer vision. It has a tremendous development in the decade with the development of deep learning. But the boundary blur of the depth map is still a serious problem. Research finds the boundary blur problem is mainly caused by two factors, first, the low-level features containing boundary and structure information may loss in deeper networks during the convolution process., second, the model ignores the errors introduced by the boundary area due to the few portions of the boundary in the whole areas during the backpropagation. In order to mitigate the boundary blur problem, we focus on the above two impact factors. Firstly, we design a scene understanding module to learn the global information with low- and high-level features, and then to transform the global information to different scales with our proposed scale transform module according to the different phases in the decoder. Secondly, we propose a boundary-aware depth loss function to pay attention to the effects of the boundary's depth value. The extensive experiments show that our method can predict the depth maps with clearer boundaries, and the performance of the depth accuracy base on NYU-depth v2 and SUN RGB-D is competitive.