Yingxue Xu

Yingxue Xu, Hao Chen

Survival prediction is a complicated ordinal regression task that aims to predict the ranking risk of death, which generally benefits from the integration of histology and genomic data. Despite the progress in joint learning from pathology and genomics, existing methods still suffer from challenging issues: 1) Due to the large size of pathological images, it is difficult to effectively represent the gigapixel whole slide images (WSIs). 2) Interactions within tumor microenvironment (TME) in histology are essential for survival analysis. Although current approaches attempt to model these interactions via co-attention between histology and genomic data, they focus on only dense local similarity across modalities, which fails to capture global consistency between potential structures, i.e. TME-related interactions of histology and co-expression of genomic data. To address these challenges, we propose a Multimodal Optimal Transport-based Co-Attention Transformer framework with global structure consistency, in which optimal transport (OT) is applied to match patches of a WSI and genes embeddings for selecting informative patches to represent the gigapixel WSI. More importantly, OT-based co-attention provides a global awareness to effectively capture structural interactions within TME for survival prediction. To overcome high computational complexity of OT, we propose a robust and efficient implementation over micro-batch of WSI patches by approximating the original OT with unbalanced mini-batch OT. Extensive experiments show the superiority of our method on five benchmark datasets compared to the state-of-the-art methods. The code is released.

Yingxue Xu, Yihui Wang, Fengtao Zhou et al.

Remarkable strides in computational pathology have been made in the task-agnostic foundation model that advances the performance of a wide array of downstream clinical tasks. Despite the promising performance, there are still several challenges. First, prior works have resorted to either vision-only or image-caption data, disregarding pathology reports with more clinically authentic information from pathologists and gene expression profiles which respectively offer distinct knowledge for versatile clinical applications. Second, the current progress in pathology FMs predominantly concentrates on the patch level, where the restricted context of patch-level pretraining fails to capture whole-slide patterns. Even recent slide-level FMs still struggle to provide whole-slide context for patch representation. In this study, for the first time, we develop a pathology foundation model incorporating three levels of modalities: pathology slides, pathology reports, and gene expression data, which resulted in 26,169 slide-level modality pairs from 10,275 patients across 32 cancer types, amounting to over 116 million pathological patch images. To leverage these data for CPath, we propose a novel whole-slide pretraining paradigm that injects the multimodal whole-slide context into the patch representation, called Multimodal Self-TAught PRetraining (mSTAR). The proposed paradigm revolutionizes the pretraining workflow for CPath, enabling the pathology FM to acquire the whole-slide context. To the best of our knowledge, this is the first attempt to incorporate three modalities at the whole-slide context for enhancing pathology FMs. To systematically evaluate the capabilities of mSTAR, we built the largest spectrum of oncological benchmark, spanning 7 categories of oncological applications in 15 types of 97 practical oncological tasks.

Yingxue Xu, Guihua Wen, Yang Hu et al.

Unsupervised domain adaptation (UDA) aims to estimate a transferable model for unlabeled target domains by exploiting labeled source data. Optimal Transport (OT) based methods have recently been proven to be a promising solution for UDA with a solid theoretical foundation and competitive performance. However, most of these methods solely focus on domain-level OT alignment by leveraging the geometry of domains for domain-invariant features based on the global embeddings of images. However, global representations of images may destroy image structure, leading to the loss of local details that offer category-discriminative information. This study proposes an end-to-end Deep Hierarchical Optimal Transport method (DeepHOT), which aims to learn both domain-invariant and category-discriminative representations by mining hierarchical structural relations among domains. The main idea is to incorporate a domain-level OT and image-level OT into a unified OT framework, hierarchical optimal transport, to model the underlying geometry in both domain space and image space. In DeepHOT framework, an image-level OT serves as the ground distance metric for the domain-level OT, leading to the hierarchical structural distance. Compared with the ground distance of the conventional domain-level OT, the image-level OT captures structural associations among local regions of images that are beneficial to classification. In this way, DeepHOT, a unified OT framework, not only aligns domains by domain-level OT, but also enhances the discriminative power through image-level OT. Moreover, to overcome the limitation of high computational complexity, we propose a robust and efficient implementation of DeepHOT by approximating origin OT with sliced Wasserstein distance in image-level OT and accomplishing the mini-batch unbalanced domain-level OT.

Jiabo Ma, Zhengrui Guo, Fengtao Zhou et al.

Foundation models pretrained on large-scale datasets are revolutionizing the field of computational pathology (CPath). The generalization ability of foundation models is crucial for the success in various downstream clinical tasks. However, current foundation models have only been evaluated on a limited type and number of tasks, leaving their generalization ability and overall performance unclear. To address this gap, we established a most comprehensive benchmark to evaluate the performance of off-the-shelf foundation models across six distinct clinical task types, encompassing a total of 72 specific tasks, including slide-level classification, survival prediction, ROI-tissue classification, ROI retrieval, visual question answering, and report generation. Our findings reveal that existing foundation models excel at certain task types but struggle to effectively handle the full breadth of clinical tasks. To improve the generalization of pathology foundation models, we propose a unified knowledge distillation framework consisting of both expert and self-knowledge distillation, where the former allows the model to learn from the knowledge of multiple expert models, while the latter leverages self-distillation to enable image representation learning via local-global alignment. Based on this framework, we curated a dataset of 96,000 whole slide images (WSIs) and developed a Generalizable Pathology Foundation Model (GPFM). This advanced model was trained on a substantial dataset comprising 190 million images extracted from approximately 72,000 publicly available slides, encompassing 34 major tissue types. Evaluated on the established benchmark, GPFM achieves an impressive average rank of 1.6, with 42 tasks ranked 1st, while the second-best model, UNI, attains an average rank of 3.7, with only 6 tasks ranked 1st.

Zhengrui Guo, Jiabo Ma, Yingxue Xu et al.

Histopathology serves as the gold standard in cancer diagnosis, with clinical reports being vital in interpreting and understanding this process, guiding cancer treatment and patient care. The automation of histopathology report generation with deep learning stands to significantly enhance clinical efficiency and lessen the labor-intensive, time-consuming burden on pathologists in report writing. In pursuit of this advancement, we introduce HistGen, a multiple instance learning-empowered framework for histopathology report generation together with the first benchmark dataset for evaluation. Inspired by diagnostic and report-writing workflows, HistGen features two delicately designed modules, aiming to boost report generation by aligning whole slide images (WSIs) and diagnostic reports from local and global granularity. To achieve this, a local-global hierarchical encoder is developed for efficient visual feature aggregation from a region-to-slide perspective. Meanwhile, a cross-modal context module is proposed to explicitly facilitate alignment and interaction between distinct modalities, effectively bridging the gap between the extensive visual sequences of WSIs and corresponding highly summarized reports. Experimental results on WSI report generation show the proposed model outperforms state-of-the-art (SOTA) models by a large margin. Moreover, the results of fine-tuning our model on cancer subtyping and survival analysis tasks further demonstrate superior performance compared to SOTA methods, showcasing strong transfer learning capability. Dataset, model weights, and source code are available in https://github.com/dddavid4real/HistGen.

Yingxue Xu, Fengtao Zhou, Chenyu Zhao et al.

The integration of multimodal data including pathology images and gene profiles is widely applied in precise survival prediction. Despite recent advances in multimodal survival models, collecting complete modalities for multimodal fusion still poses a significant challenge, hindering their application in clinical settings. Current approaches tackling incomplete modalities often fall short, as they typically compensate for only a limited part of the knowledge of missing modalities. To address this issue, we propose a Distilled Prompt Learning framework (DisPro) to utilize the strong robustness of Large Language Models (LLMs) to missing modalities, which employs two-stage prompting for compensation of comprehensive information for missing modalities. In the first stage, Unimodal Prompting (UniPro) distills the knowledge distribution of each modality, preparing for supplementing modality-specific knowledge of the missing modality in the subsequent stage. In the second stage, Multimodal Prompting (MultiPro) leverages available modalities as prompts for LLMs to infer the missing modality, which provides modality-common information. Simultaneously, the unimodal knowledge acquired in the first stage is injected into multimodal inference to compensate for the modality-specific knowledge of the missing modality. Extensive experiments covering various missing scenarios demonstrated the superiority of the proposed method. The code is available at https://github.com/Innse/DisPro.

Jiarui Ouyang, Yihui Wang, Yihang Gao et al.

Spatial Transcriptomics (ST) offers spatially resolved gene expression but remains costly. Predicting expression directly from widely available Hematoxylin and Eosin (H&E) stained images presents a cost-effective alternative. However, most computational approaches (i) predict each gene independently, overlooking co-expression structure, and (ii) cast the task as continuous regression despite expression being discrete counts. This mismatch can yield biologically implausible outputs and complicate downstream analyses. We introduce GenAR, a multi-scale autoregressive framework that refines predictions from coarse to fine. GenAR clusters genes into hierarchical groups to expose cross-gene dependencies, models expression as codebook-free discrete token generation to directly predict raw counts, and conditions decoding on fused histological and spatial embeddings. From an information-theoretic perspective, the discrete formulation avoids log-induced biases and the coarse-to-fine factorization aligns with a principled conditional decomposition. Extensive experimental results on four Spatial Transcriptomics datasets across different tissue types demonstrate that GenAR achieves state-of-the-art performance, offering potential implications for precision medicine and cost-effective molecular profiling. Code is publicly available at https://github.com/oyjr/genar.

Yilan Zhang, Yingxue Xu, Jianqi Chen et al.

Multimodal learning significantly benefits cancer survival prediction, especially the integration of pathological images and genomic data. Despite advantages of multimodal learning for cancer survival prediction, massive redundancy in multimodal data prevents it from extracting discriminative and compact information: (1) An extensive amount of intra-modal task-unrelated information blurs discriminability, especially for gigapixel whole slide images (WSIs) with many patches in pathology and thousands of pathways in genomic data, leading to an ``intra-modal redundancy" issue. (2) Duplicated information among modalities dominates the representation of multimodal data, which makes modality-specific information prone to being ignored, resulting in an ``inter-modal redundancy" issue. To address these, we propose a new framework, Prototypical Information Bottlenecking and Disentangling (PIBD), consisting of Prototypical Information Bottleneck (PIB) module for intra-modal redundancy and Prototypical Information Disentanglement (PID) module for inter-modal redundancy. Specifically, a variant of information bottleneck, PIB, is proposed to model prototypes approximating a bunch of instances for different risk levels, which can be used for selection of discriminative instances within modality. PID module decouples entangled multimodal data into compact distinct components: modality-common and modality-specific knowledge, under the guidance of the joint prototypical distribution. Extensive experiments on five cancer benchmark datasets demonstrated our superiority over other methods.

Zhikang Wang, Yumeng Zhang, Yingxue Xu et al.

Histo-genomic multi-modal methods have recently emerged as a powerful paradigm, demonstrating significant potential for improving cancer prognosis. However, genome sequencing, unlike histopathology imaging, is still not widely accessible in underdeveloped regions, limiting the application of these multi-modal approaches in clinical settings. To address this, we propose a novel Genome-informed Hyper-Attention Network, termed G-HANet, which is capable of effectively distilling the histo-genomic knowledge during training to elevate uni-modal whole slide image (WSI)-based inference for the first time. Compared with traditional knowledge distillation methods (i.e., teacher-student architecture) in other tasks, our end-to-end model is superior in terms of training efficiency and learning cross-modal interactions. Specifically, the network comprises the cross-modal associating branch (CAB) and hyper-attention survival branch (HSB). Through the genomic data reconstruction from WSIs, CAB effectively distills the associations between functional genotypes and morphological phenotypes and offers insights into the gene expression profiles in the feature space. Subsequently, HSB leverages the distilled histo-genomic associations as well as the generated morphology-based weights to achieve the hyper-attention modeling of the patients from both histopathology and genomic perspectives to improve cancer prognosis. Extensive experiments are conducted on five TCGA benchmarking datasets and the results demonstrate that G-HANet significantly outperforms the state-of-the-art WSI-based methods and achieves competitive performance with genome-based and multi-modal methods. G-HANet is expected to be explored as a useful tool by the research community to address the current bottleneck of insufficient histo-genomic data pairing in the context of cancer prognosis and precision oncology.

Huajun Zhou, Fengtao Zhou, Jiabo Ma et al.

Multimodal data provides heterogeneous information for a holistic understanding of the tumor microenvironment. However, existing AI models often struggle to harness the rich information within multimodal data and extract poorly generalizable representations. Here we present MICE (Multimodal data Integration via Collaborative Experts), a multimodal foundation model that effectively integrates pathology images, clinical reports, and genomics data for precise pan-cancer prognosis prediction. Instead of conventional multi-expert modules, MICE employs multiple functionally diverse experts to comprehensively capture both cross-cancer and cancer-specific insights. Leveraging data from 11,799 patients across 30 cancer types, we enhanced MICE's generalizability by coupling contrastive and supervised learning. MICE outperformed both unimodal and state-of-the-art multi-expert-based multimodal models, demonstrating substantial improvements in C-index ranging from 3.8% to 11.2% on internal cohorts and 5.8% to 8.8% on independent cohorts, respectively. Moreover, it exhibited remarkable data efficiency across diverse clinical scenarios. With its enhanced generalizability and data efficiency, MICE establishes an effective and scalable foundation for pan-cancer prognosis prediction, holding strong potential to personalize tailored therapies and improve treatment outcomes.

Cheng Jin, Fengtao Zhou, Yunfang Yu et al.

Precision oncology requires accurate molecular insights, yet obtaining these directly from genomics is costly and time-consuming for broad clinical use. Predicting complex molecular features and patient prognosis directly from routine whole-slide images (WSI) remains a major challenge for current deep learning methods. Here we introduce PathLUPI, which uses transcriptomic privileged information during training to extract genome-anchored histological embeddings, enabling effective molecular prediction using only WSIs at inference. Through extensive evaluation across 49 molecular oncology tasks using 11,257 cases among 20 cohorts, PathLUPI demonstrated superior performance compared to conventional methods trained solely on WSIs. Crucially, it achieves AUC $\geq$ 0.80 in 14 of the biomarker prediction and molecular subtyping tasks and C-index $\geq$ 0.70 in survival cohorts of 5 major cancer types. Moreover, PathLUPI embeddings reveal distinct cellular morphological signatures associated with specific genotypes and related biological pathways within WSIs. By effectively encoding molecular context to refine WSI representations, PathLUPI overcomes a key limitation of existing models and offers a novel strategy to bridge molecular insights with routine pathology workflows for wider clinical application.

Yang Hu, Guihua Wen, Adriane Chapman et al.

Zero-shot learning uses semantic attributes to connect the search space of unseen objects. In recent years, although the deep convolutional network brings powerful visual modeling capabilities to the ZSL task, its visual features have severe pattern inertia and lack of representation of semantic relationships, which leads to severe bias and ambiguity. In response to this, we propose the Graph-based Visual-Semantic Entanglement Network to conduct graph modeling of visual features, which is mapped to semantic attributes by using a knowledge graph, it contains several novel designs: 1. it establishes a multi-path entangled network with the convolutional neural network (CNN) and the graph convolutional network (GCN), which input the visual features from CNN to GCN to model the implicit semantic relations, then GCN feedback the graph modeled information to CNN features; 2. it uses attribute word vectors as the target for the graph semantic modeling of GCN, which forms a self-consistent regression for graph modeling and supervise GCN to learn more personalized attribute relations; 3. it fuses and supplements the hierarchical visual-semantic features refined by graph modeling into visual embedding. Our method outperforms state-of-the-art approaches on multiple representative ZSL datasets: AwA2, CUB, and SUN by promoting the semantic linkage modelling of visual features.

Yingxue Xu, Guihua Wen, Yang Hu et al.

Chinese herbs play a critical role in Traditional Chinese Medicine. Due to different recognition granularity, they can be recognized accurately only by professionals with much experience. It is expected that they can be recognized automatically using new techniques like machine learning. However, there is no Chinese herbal image dataset available. Simultaneously, there is no machine learning method which can deal with Chinese herbal image recognition well. Therefore, this paper begins with building a new standard Chinese-Herbs dataset. Subsequently, a new Attentional Pyramid Networks (APN) for Chinese herbal recognition is proposed, where both novel competitive attention and spatial collaborative attention are proposed and then applied. APN can adaptively model Chinese herbal images with different feature scales. Finally, a new framework for Chinese herbal recognition is proposed as a new application of APN. Experiments are conducted on our constructed dataset and validate the effectiveness of our methods.

Mingnan Luo, Guihua Wen, Yang Hu et al.

Global Average Pooling (GAP) is used by default on the channel-wise attention mechanism to extract channel descriptors. However, the simple global aggregation method of GAP is easy to make the channel descriptors have homogeneity, which weakens the detail distinction between feature maps, thus affecting the performance of the attention mechanism. In this work, we propose a novel method for channel-wise attention network, called Stochastic Region Pooling (SRP), which makes the channel descriptors more representative and diversity by encouraging the feature map to have more or wider important feature responses. Also, SRP is the general method for the attention mechanisms without any additional parameters or computation. It can be widely applied to attention networks without modifying the network structure. Experimental results on image recognition datasets including CIAFR-10/100, ImageNet and three Fine-grained datasets (CUB-200-2011, Stanford Cars and Stanford Dogs) show that SRP brings the significant improvements of the performance over efficient CNNs and achieves the state-of-the-art results.

Yingxue Xu, Guihua Wen, Yang Hu et al.

Convolution neural netwotks (CNNs) are successfully applied in image recognition task. In this study, we explore the approach of automatic herbal recognition with CNNs and build the standard Chinese herbs datasets firstly. According to the characteristics of herbal images, we proposed the competitive attentional fusion pyramid networks to model the features of herbal image, which mdoels the relationship of feature maps from different levels, and re-weights multi-level channels with channel-wise attention mechanism. In this way, we can dynamically adjust the weight of feature maps from various layers, according to the visual characteristics of each herbal image. Moreover, we also introduce the spatial attention to recalibrate the misaligned features caused by sampling in features amalgamation. Extensive experiments are conducted on our proposed datasets and validate the superior performance of our proposed models. The Chinese herbs datasets will be released upon acceptance to facilitate the research of Chinese herbal recognition.