Ke Yuan

Adalberto Claudio Quiros, Nicolas Coudray, Anna Yeaton et al.

Definitive cancer diagnosis and management depend upon the extraction of information from microscopy images by pathologists. These images contain complex information requiring time-consuming expert human interpretation that is prone to human bias. Supervised deep learning approaches have proven powerful for classification tasks, but they are inherently limited by the cost and quality of annotations used for training these models. To address this limitation of supervised methods, we developed Histomorphological Phenotype Learning (HPL), a fully blue{self-}supervised methodology that requires no expert labels or annotations and operates via the automatic discovery of discriminatory image features in small image tiles. Tiles are grouped into morphologically similar clusters which constitute a library of histomorphological phenotypes, revealing trajectories from benign to malignant tissue via inflammatory and reactive phenotypes. These clusters have distinct features which can be identified using orthogonal methods, linking histologic, molecular and clinical phenotypes. Applied to lung cancer tissues, we show that they align closely with patient survival, with histopathologically recognised tumor types and growth patterns, and with transcriptomic measures of immunophenotype. We then demonstrate that these properties are maintained in a multi-cancer study. These results show the clusters represent recurrent host responses and modes of tumor growth emerging under natural selection. Code, pre-trained models, learned embeddings, and documentation are available to the community at https://github.com/AdalbertoCq/Histomorphological-Phenotype-Learning

Farzaneh Seyedshahi, Francesca Damiola, Sylvie Lantuejoul et al.

Accurate subtype classification and outcome prediction in mesothelioma are essential for guiding therapy and patient care. Most computational pathology models are trained on large tissue images from resection specimens, limiting their use in real-world settings where small biopsies are common. We show that a self-supervised encoder trained on resection tissue can be applied to biopsy material, capturing meaningful morphological patterns. Using these patterns, the model can predict patient survival and classify tumor subtypes. This approach demonstrates the potential of AI-driven tools to support diagnosis and treatment planning in mesothelioma.

Zhaohan Meng, Zhen Bai, Ke Yuan et al.

Protein-ligand modeling underpins computational drug discovery and molecular design. Existing protein-ligand benchmarks typically evaluate whether a protein and ligand interact and how strongly they bind, through tasks such as binary binding prediction and affinity regression. However, these evaluations provide limited evidence of whether models can localize binding sites or identify the non-covalent interactions underlying molecular recognition. To address this gap, we introduce InteractBind, a large-scale protein-ligand dataset comprising approximately 100k protein-ligand pairs, together with a benchmark for fine-grained evaluation. The core fine-grained task is that of binding-site localization, which uses protein-residue and ligand-atom interaction maps spanning six major types of non-covalent interactions to assess whether model-derived interaction maps localize binding sites. InteractBind further includes binding affinity and protein similarity-controlled splits to support realistic generalization assessment. Using InteractBind, we evaluate eight existing sequence-based and interaction-aware models, assessing binary binding prediction and binding-site localization. Results reveal limited binding-site localization despite strong binary binding prediction, with marked variation across non-covalent interaction types. Overall, InteractBind establishes a benchmark paradigm that encourages the development of more interpretable and physically grounded protein-ligand models.

Zhengqi Xu, Ke Yuan, Huiqiong Wang et al.

Recently, model merging techniques have surfaced as a solution to combine multiple single-talent models into a single multi-talent model. However, previous endeavors in this field have either necessitated additional training or fine-tuning processes, or require that the models possess the same pre-trained initialization. In this work, we identify a common drawback in prior works w.r.t. the inconsistency of unit similarity in the weight space and the activation space. To address this inconsistency, we propose an innovative model merging framework, coined as merging under dual-space constraints (MuDSC). Specifically, instead of solely maximizing the objective of a single space, we advocate for the exploration of permutation matrices situated in a region with a unified high similarity in the dual space, achieved through the linear combination of activation and weight similarity matrices. In order to enhance usability, we have also incorporated adaptations for group structure, including Multi-Head Attention and Group Normalization. Comprehensive experimental comparisons demonstrate that MuDSC can significantly boost the performance of merged models with various task combinations and architectures. Furthermore, the visualization of the merged model within the multi-task loss landscape reveals that MuDSC enables the merged model to reside in the overlapping segment, featuring a unified lower loss for each task. Our code is publicly available at https://github.com/zju-vipa/training_free_model_merging.

Lucas Farndale, Robert Insall, Ke Yuan

Medical imaging technologies are generating increasingly large amounts of high-quality, information-dense data. Despite the progress, practical use of advanced imaging technologies for research and diagnosis remains limited by cost and availability, so information-sparse data such as H&E stains are relied on in practice. The study of diseased tissue requires methods which can leverage these information-dense data to extract more value from routine, information-sparse data. Using self-supervised deep learning, we demonstrate that it is possible to distil knowledge during training from information-dense data into models which only require information-sparse data for inference. This improves downstream classification accuracy on information-sparse data, making it comparable with the fully-supervised baseline. We find substantial effects on the learned representations, and this training process identifies subtle features which otherwise go undetected. This approach enables the design of models which require only routine images, but contain insights from state-of-the-art data, allowing better use of the available resources.

Adalberto Claudio Quiros, Nicolas Coudray, Anna Yeaton et al.

Deep learning based analysis of histopathology images shows promise in advancing the understanding of tumor progression, tumor micro-environment, and their underpinning biological processes. So far, these approaches have focused on extracting information associated with annotations. In this work, we ask how much information can be learned from the tissue architecture itself. We present an adversarial learning model to extract feature representations of cancer tissue, without the need for manual annotations. We show that these representations are able to identify a variety of morphological characteristics across three cancer types: Breast, colon, and lung. This is supported by 1) the separation of morphologic characteristics in the latent space; 2) the ability to classify tissue type with logistic regression using latent representations, with an AUC of 0.97 and 85% accuracy, comparable to supervised deep models; 3) the ability to predict the presence of tumor in Whole Slide Images (WSIs) using multiple instance learning (MIL), achieving an AUC of 0.98 and 94% accuracy. Our results show that our model captures distinct phenotypic characteristics of real tissue samples, paving the way for further understanding of tumor progression and tumor micro-environment, and ultimately refining histopathological classification for diagnosis and treatment. The code and pretrained models are available at: https://github.com/AdalbertoCq/Adversarial-learning-of-cancer-tissue-representations

Adalberto Claudio Quiros, Roderick Murray-Smith, Ke Yuan

Histopathological images of tumors contain abundant information about how tumors grow and how they interact with their micro-environment. Better understanding of tissue phenotypes in these images could reveal novel determinants of pathological processes underlying cancer, and in turn improve diagnosis and treatment options. Advances of Deep learning makes it ideal to achieve those goals, however, its application is limited by the cost of high quality labels from patients data. Unsupervised learning, in particular, deep generative models with representation learning properties provides an alternative path to further understand cancer tissue phenotypes, capturing tissue morphologies. In this paper, we develop a framework which allows GANs to capture key tissue features and uses these characteristics to give structure to its latent space. To this end, we trained our model on two different datasets, an H&E colorectal cancer tissue from the National Center for Tumor diseases (NCT) and an H&E breast cancer tissue from the Netherlands Cancer Institute (NKI) and Vancouver General Hospital (VGH). Composed of 86 slide images and 576 TMAs respectively. We show that our model generates high quality images, with a FID of 16.65 (breast cancer) and 32.05 (colorectal cancer). We further assess the quality of the images with cancer tissue characteristics (e.g. count of cancer, lymphocytes, or stromal cells), using quantitative information to calculate the FID and showing consistent performance of 9.86. Additionally, the latent space of our model shows an interpretable structure and allows semantic vector operations that translate into tissue feature transformations. Furthermore, ratings from two expert pathologists found no significant difference between our generated tissue images from real ones. The code, images, and pretrained models are available at https://github.com/AdalbertoCq/Pathology-GAN

Lucas Farndale, Robert Insall, Ke Yuan

Computational pathology models rarely utilise data that will not be available for inference. This means most models cannot learn from highly informative data such as additional immunohistochemical (IHC) stains and spatial transcriptomics. We present TriDeNT, a novel self-supervised method for utilising privileged data that is not available during inference to improve performance. We demonstrate the efficacy of this method for a range of different paired data including immunohistochemistry, spatial transcriptomics and expert nuclei annotations. In all settings, TriDeNT outperforms other state-of-the-art methods in downstream tasks, with observed improvements of up to 101%. Furthermore, we provide qualitative and quantitative measurements of the features learned by these models and how they differ from baselines. TriDeNT offers a novel method to distil knowledge from scarce or costly data during training, to create significantly better models for routine inputs.

Lucas Farndale, Chris Walsh, Robert Insall et al.

Multimodal self-supervised representation learning has consistently proven to be a highly effective method in medical image analysis, offering strong task performance and producing biologically informed insights. However, these methods heavily rely on large, paired datasets, which is prohibitive for their use in scenarios where paired data does not exist, or there is only a small amount available. In contrast, image generation methods can work well on very small datasets, and can find mappings between unpaired datasets, meaning an effectively unlimited amount of paired synthetic data can be generated. In this work, we demonstrate that representation learning can be significantly improved by synthetically generating paired information, both compared to training on either single-modality (up to 4.4x error reduction) or authentic multi-modal paired datasets (up to 5.6x error reduction).

Lucas Farndale, Paul Henderson, Edward W Roberts et al.

Self-supervised representation learning methods often fail to learn subtle or complex features, which can be dominated by simpler patterns which are much easier to learn. This limitation is particularly problematic in applications to science and engineering, as complex features can be critical for discovery and analysis. To address this, we introduce Split Component Embedding Registration (SpliCER), a novel architecture which splits the image into sections and distils information from each section to guide the model to learn more subtle and complex features without compromising on simpler features. SpliCER is compatible with any self-supervised loss function and can be integrated into existing methods without modification. The primary contributions of this work are as follows: i) we demonstrate that existing self-supervised methods can learn shortcut solutions when simple and complex features are both present; ii) we introduce a novel self-supervised training method, SpliCER, to overcome the limitations of existing methods, and achieve significant downstream performance improvements; iii) we demonstrate the effectiveness of SpliCER in cutting-edge medical and geospatial imaging settings. SpliCER offers a powerful new tool for representation learning, enabling models to uncover complex features which could be overlooked by other methods.

Ke Yuan, Yaoxin Liu, Shriyesh Chandra et al.

This project focuses on analyzing retail market trends using historical sales data, search trends, and customer reviews. By identifying the patterns and trending products, the analysis provides actionable insights for retailers to optimize inventory management and marketing strategies, ultimately enhancing customer satisfaction and maximizing revenue.

Zhaohan Meng, Zaiqiao Meng, Ke Yuan et al.

Predicting drug-target interaction (DTI) is critical in the drug discovery process. Despite remarkable advances in recent DTI models through the integration of representations from diverse drug and target encoders, such models often struggle to capture the fine-grained interactions between drugs and protein, i.e. the binding of specific drug atoms (or substructures) and key amino acids of proteins, which is crucial for understanding the binding mechanisms and optimising drug design. To address this issue, this paper introduces a novel model, called FusionDTI, which uses a token-level Fusion module to effectively learn fine-grained information for Drug-Target Interaction. In particular, our FusionDTI model uses the SELFIES representation of drugs to mitigate sequence fragment invalidation and incorporates the structure-aware (SA) vocabulary of target proteins to address the limitation of amino acid sequences in structural information, additionally leveraging pre-trained language models extensively trained on large-scale biomedical datasets as encoders to capture the complex information of drugs and targets. Experiments on three well-known benchmark datasets show that our proposed FusionDTI model achieves the best performance in DTI prediction compared with seven existing state-of-the-art baselines. Furthermore, our case study indicates that FusionDTI could highlight the potential binding sites, enhancing the explainability of the DTI prediction.

Shuai Peng, Ke Yuan, Liangcai Gao et al.

Large-scale pre-trained models like BERT, have obtained a great success in various Natural Language Processing (NLP) tasks, while it is still a challenge to adapt them to the math-related tasks. Current pre-trained models neglect the structural features and the semantic correspondence between formula and its context. To address these issues, we propose a novel pre-trained model, namely \textbf{MathBERT}, which is jointly trained with mathematical formulas and their corresponding contexts. In addition, in order to further capture the semantic-level structural features of formulas, a new pre-training task is designed to predict the masked formula substructures extracted from the Operator Tree (OPT), which is the semantic structural representation of formulas. We conduct various experiments on three downstream tasks to evaluate the performance of MathBERT, including mathematical information retrieval, formula topic classification and formula headline generation. Experimental results demonstrate that MathBERT significantly outperforms existing methods on all those three tasks. Moreover, we qualitatively show that this pre-trained model effectively captures the semantic-level structural information of formulas. To the best of our knowledge, MathBERT is the first pre-trained model for mathematical formula understanding.

Ke Yuan, Zuoyu Yan, Yibo Li et al.

Math expressions are important parts of scientific and educational documents, but some of them may be challenging for junior scholars or students to understand. Nevertheless, constructing textual descriptions for math expressions is nontrivial. In this paper, we explore the feasibility to automatically construct descriptions for math expressions. But there are two challenges that need to be addressed: 1) finding relevant documents since a math equation understanding usually requires several topics, but these topics are often explained in different documents. 2) the sparsity of the collected relevant documents making it difficult to extract reasonable descriptions. Different documents mainly focus on different topics which makes model hard to extract salient information and organize them to form a description of math expressions. To address these issues, we propose a hybrid model (MathDes) which contains two important modules: Selector and Summarizer. In the Selector, a Topic Relation Graph (TRG) is proposed to obtain the relevant documents which contain the comprehensive information of math expressions. TRG is a graph built according to the citations between expressions. In the Summarizer, a summarization model under the Integer Linear Programming (ILP) framework is proposed. This module constructs the final description with the help of a timeline that is extracted from TRG. The experimental results demonstrate that our methods are promising for this task and outperform the baselines in all aspects.

Zuoyu Yan, Xiaode Zhang, Liangcai Gao et al.

Despite the recent advances in optical character recognition (OCR), mathematical expressions still face a great challenge to recognize due to their two-dimensional graphical layout. In this paper, we propose a convolutional sequence modeling network, ConvMath, which converts the mathematical expression description in an image into a LaTeX sequence in an end-to-end way. The network combines an image encoder for feature extraction and a convolutional decoder for sequence generation. Compared with other Long Short Term Memory(LSTM) based encoder-decoder models, ConvMath is entirely based on convolution, thus it is easy to perform parallel computation. Besides, the network adopts multi-layer attention mechanism in the decoder, which allows the model to align output symbols with source feature vectors automatically, and alleviates the problem of lacking coverage while training the model. The performance of ConvMath is evaluated on an open dataset named IM2LATEX-100K, including 103556 samples. The experimental results demonstrate that the proposed network achieves state-of-the-art accuracy and much better efficiency than previous methods.

Adalberto Claudio Quiros, Roderick Murray-Smith, Ke Yuan

Application of deep learning in digital pathology shows promise on improving disease diagnosis and understanding. We present a deep generative model that learns to simulate high-fidelity cancer tissue images while mapping the real images onto an interpretable low dimensional latent space. The key to the model is an encoder trained by a previously developed generative adversarial network, PathologyGAN. We study the latent space using 249K images from two breast cancer cohorts. We find that the latent space encodes morphological characteristics of tissues (e.g. patterns of cancer, lymphocytes, and stromal cells). In addition, the latent space reveals distinctly enriched clusters of tissue architectures in the high-risk patient group.

Ke Yuan, Dafang He, Zhuoren Jiang et al.

Mathematical equations are an important part of dissemination and communication of scientific information. Students, however, often feel challenged in reading and understanding math content and equations. With the development of the Web, students are posting their math questions online. Nevertheless, constructing a concise math headline that gives a good description of the posted detailed math question is nontrivial. In this study, we explore a novel summarization task denoted as geNerating A concise Math hEadline from a detailed math question (NAME). Compared to conventional summarization tasks, this task has two extra and essential constraints: 1) Detailed math questions consist of text and math equations which require a unified framework to jointly model textual and mathematical information; 2) Unlike text, math equations contain semantic and structural features, and both of them should be captured together. To address these issues, we propose MathSum, a novel summarization model which utilizes a pointer mechanism combined with a multi-head attention mechanism for mathematical representation augmentation. The pointer mechanism can either copy textual tokens or math tokens from source questions in order to generate math headlines. The multi-head attention mechanism is designed to enrich the representation of math equations by modeling and integrating both its semantic and structural features. For evaluation, we collect and make available two sets of real-world detailed math questions along with human-written math headlines, namely EXEQ-300k and OFEQ-10k. Experimental results demonstrate that our model (MathSum) significantly outperforms state-of-the-art models for both the EXEQ-300k and OFEQ-10k datasets.

Zhuoren Jiang, Liangcai Gao, Ke Yuan et al.

Although the scientific digital library is growing at a rapid pace, scholars/students often find reading Science, Technology, Engineering, and Mathematics (STEM) literature daunting, especially for the math-content/formula. In this paper, we propose a novel problem, ``mathematics content understanding'', for cyberlearning and cyberreading. To address this problem, we create a Formula Evolution Map (FEM) offline and implement a novel online learning/reading environment, PDF Reader with Math-Assistant (PRMA), which incorporates innovative math-scaffolding methods. The proposed algorithm/system can auto-characterize student emerging math-information need while reading a paper and enable students to readily explore the formula evolution trajectory in FEM. Based on a math-information need, PRMA utilizes innovative joint embedding, formula evolution mining, and heterogeneous graph mining algorithms to recommend high quality Open Educational Resources (OERs), e.g., video, Wikipedia page, or slides, to help students better understand the math-content in the paper. Evaluation and exit surveys show that the PRMA system and the proposed formula understanding algorithm can effectively assist master and PhD students better understand the complex math-content in the class readings.

Liangcai Gao, Zhuoren Jiang, Yue Yin et al.

While neural network approaches are achieving breakthrough performance in the natural language related fields, there have been few similar attempts at mathematical language related tasks. In this study, we explore the potential of applying neural representation techniques to Mathematical Information Retrieval (MIR) tasks. In more detail, we first briefly analyze the characteristic differences between natural language and mathematical language. Then we design a "symbol2vec" method to learn the vector representations of formula symbols (numbers, variables, operators, functions, etc.) Finally, we propose a "formula2vec" based MIR approach and evaluate its performance. Preliminary experiment results show that there is a promising potential for applying formula embedding models to mathematical language representation and MIR tasks.