Junhao Wen

Rongguang Wang, Vishnu Bashyam, Zhijian Yang et al.

Generative adversarial networks (GANs) are one powerful type of deep learning models that have been successfully utilized in numerous fields. They belong to a broader family called generative methods, which generate new data with a probabilistic model by learning sample distribution from real examples. In the clinical context, GANs have shown enhanced capabilities in capturing spatially complex, nonlinear, and potentially subtle disease effects compared to traditional generative methods. This review appraises the existing literature on the applications of GANs in imaging studies of various neurological conditions, including Alzheimer's disease, brain tumors, brain aging, and multiple sclerosis. We provide an intuitive explanation of various GAN methods for each application and further discuss the main challenges, open questions, and promising future directions of leveraging GANs in neuroimaging. We aim to bridge the gap between advanced deep learning methods and neurology research by highlighting how GANs can be leveraged to support clinical decision making and contribute to a better understanding of the structural and functional patterns of brain diseases.

Zhijian Yang, Junhao Wen, Christos Davatzikos

A plethora of machine learning methods have been applied to imaging data, enabling the construction of clinically relevant imaging signatures of neurological and neuropsychiatric diseases. Oftentimes, such methods don't explicitly model the heterogeneity of disease effects, or approach it via nonlinear models that are not interpretable. Moreover, unsupervised methods may parse heterogeneity that is driven by nuisance confounding factors that affect brain structure or function, rather than heterogeneity relevant to a pathology of interest. On the other hand, semi-supervised clustering methods seek to derive a dichotomous subtype membership, ignoring the truth that disease heterogeneity spatially and temporally extends along a continuum. To address the aforementioned limitations, herein, we propose a novel method, termed Surreal-GAN (Semi-SUpeRvised ReprEsentAtion Learning via GAN). Using cross-sectional imaging data, Surreal-GAN dissects underlying disease-related heterogeneity under the principle of semi-supervised clustering (cluster mappings from normal control to patient), proposes a continuously dimensional representation, and infers the disease severity of patients at individual level along each dimension. The model first learns a transformation function from normal control (CN) domain to the patient (PT) domain with latent variables controlling transformation directions. An inverse mapping function together with regularization on function continuity, pattern orthogonality and monotonicity was also imposed to make sure that the transformation function captures necessarily meaningful imaging patterns with clinical significance. We first validated the model through extensive semi-synthetic experiments, and then demonstrate its potential in capturing biologically plausible imaging patterns in Alzheimer's disease (AD).

Zhijian Yang, Junhao Wen, Ahmed Abdulkadir et al.

Disease heterogeneity has been a critical challenge for precision diagnosis and treatment, especially in neurologic and neuropsychiatric diseases. Many diseases can display multiple distinct brain phenotypes across individuals, potentially reflecting disease subtypes that can be captured using MRI and machine learning methods. However, biological interpretability and treatment relevance are limited if the derived subtypes are not associated with genetic drivers or susceptibility factors. Herein, we describe Gene-SGAN - a multi-view, weakly-supervised deep clustering method - which dissects disease heterogeneity by jointly considering phenotypic and genetic data, thereby conferring genetic correlations to the disease subtypes and associated endophenotypic signatures. We first validate the generalizability, interpretability, and robustness of Gene-SGAN in semi-synthetic experiments. We then demonstrate its application to real multi-site datasets from 28,858 individuals, deriving subtypes of Alzheimer's disease and brain endophenotypes associated with hypertension, from MRI and SNP data. Derived brain phenotypes displayed significant differences in neuroanatomical patterns, genetic determinants, biological and clinical biomarkers, indicating potentially distinct underlying neuropathologic processes, genetic drivers, and susceptibility factors. Overall, Gene-SGAN is broadly applicable to disease subtyping and endophenotype discovery, and is herein tested on disease-related, genetically-driven neuroimaging phenotypes.

Junhao Wen, Juncen Zhou, Junjie Huang

Web3 prediction markets, exemplified by Polymarket, have gained prominence for leveraging collective intelligence to forecast a wide range of social, political, and sports events. However, among the thousands of prediction market events, consensus disputes still arise due to imperfections in market mechanisms. On Polymarket alone, the trading volume involving disputed events has reached $972,370,804.71, underscoring the critical need for objective and efficient dispute resolution. In this study, we introduce large language models (LLMs) to: (1) evaluate whether web-enabled LLMs can reproduce the decision quality of UMA's on-chain voting process once a dispute has been raised, and (2) predict, based on event rules, which market events are likely to face future disputes before they occur. Our findings show that LLMs are unable to reliably predict which events will become disputed in advance; however, once a dispute is initiated, web-enabled LLMs achieve 89.58% agreement with UMA's final resolutions and demonstrate strong stability.

Shutong Qiao, Wei Zhou, Junhao Wen et al.

Session-based recommendation (SBR) methods often rely on user behavior data, which can struggle with the sparsity of session data, limiting performance. Researchers have identified that beyond behavioral signals, rich semantic information in item descriptions is crucial for capturing hidden user intent. While large language models (LLMs) offer new ways to leverage this semantic data, the challenges of session anonymity, short-sequence nature, and high LLM training costs have hindered the development of a lightweight, efficient LLM framework for SBR. To address the above challenges, we propose an LLM-enhanced SBR framework that integrates semantic and behavioral signals from multiple views. This two-stage framework leverages the strengths of both LLMs and traditional SBR models while minimizing training costs. In the first stage, we use multi-view prompts to infer latent user intentions at the session semantic level, supported by an intent localization module to alleviate LLM hallucinations. In the second stage, we align and unify these semantic inferences with behavioral representations, effectively merging insights from both large and small models. Extensive experiments on two real datasets demonstrate that the LLM4SBR framework can effectively improve model performance. We release our codes along with the baselines at https://github.com/tsinghua-fib-lab/LLM4SBR.

Junhao Wen, Elina Thibeau-Sutre, Mauricio Diaz-Melo et al.

Over 30 papers have proposed to use convolutional neural network (CNN) for AD classification from anatomical MRI. However, the classification performance is difficult to compare across studies due to variations in components such as participant selection, image preprocessing or validation procedure. Moreover, these studies are hardly reproducible because their frameworks are not publicly accessible and because implementation details are lacking. Lastly, some of these papers may report a biased performance due to inadequate or unclear validation or model selection procedures. In the present work, we aim to address these limitations through three main contributions. First, we performed a systematic literature review and found that more than half of the surveyed papers may have suffered from data leakage. Our second contribution is the extension of our open-source framework for classification of AD using CNN and T1-weighted MRI. Finally, we used this framework to rigorously compare different CNN architectures. The data was split into training/validation/test sets at the very beginning and only the training/validation sets were used for model selection. To avoid any overfitting, the test sets were left untouched until the end of the peer-review process. Overall, the different 3D approaches (3D-subject, 3D-ROI, 3D-patch) achieved similar performances while that of the 2D slice approach was lower. Of note, the different CNN approaches did not perform better than a SVM with voxel-based features. The different approaches generalized well to similar populations but not to datasets with different inclusion criteria or demographical characteristics.

Junhao Wen, Jorge Samper-Gonzalez, Simona Bottani et al.

Diffusion MRI is the modality of choice to study alterations of white matter. In past years, various works have used diffusion MRI for automatic classification of AD. However, classification performance obtained with different approaches is difficult to compare and these studies are also difficult to reproduce. In the present paper, we first extend a previously proposed framework to diffusion MRI data for AD classification. Specifically, we add: conversion of diffusion MRI ADNI data into the BIDS standard and pipelines for diffusion MRI preprocessing and feature extraction. We then apply the framework to compare different components. First, FS has a positive impact on classification results: highest balanced accuracy (BA) improved from 0.76 to 0.82 for task CN vs AD. Secondly, voxel-wise features generally gives better performance than regional features. Fractional anisotropy (FA) and mean diffusivity (MD) provided comparable results for voxel-wise features. Moreover, we observe that the poor performance obtained in tasks involving MCI were potentially caused by the small data samples, rather than by the data imbalance. Furthermore, no extensive classification difference exists for different degree of smoothing and registration methods. Besides, we demonstrate that using non-nested validation of FS leads to unreliable and over-optimistic results: 0.05 up to 0.40 relative increase in BA. Lastly, with proper FR and FS, the performance of diffusion MRI features is comparable to that of T1w MRI. All the code of the framework and the experiments are publicly available: general-purpose tools have been integrated into the Clinica software package (www.clinica.run) and the paper-specific code is available at: https://github.com/aramis-lab/AD-ML.

Juntao Hu, Wei Zhou, Haini Cai et al.

In Sequential Recommendation Systems (SRSs), Transformer models have demonstrated remarkable performance but face computational and memory cost challenges, especially when modeling long-term user behavior sequences. Due to its quadratic complexity, the dot-product attention mechanism in Transformers becomes expensive for processing long sequences. By approximating the dot-product attention using elaborate mapping functions, linear attention provides a more efficient option with linear complexity. However, existing linear attention methods face three limitations: 1) they often use learnable position encodings, which incur extra computational costs in long-term sequence scenarios, 2) limited by the low-rank deficiency, they may not sufficiently account for user's fine-grained local preferences (short-lived burst of interest), and 3) they try to capture some temporary activities, but often confuse these with stable and long-term interests. This can result in unclear or less effective recommendations. To remedy these drawbacks, we propose a long-term sequential Recommendation model with Gated Rotary Enhanced Linear Attention (RecGRELA). Specifically, we first propose a Rotary-Enhanced Linear Attention (RELA) module to efficiently model long-range dependency within the user's historical information using rotary position encodings. Then, to address the low-rank deficiency of linear attention, we introduce an Adaptive Rank Modulator. It incorporates a rank augmentation branch to explicitly inject local token mixing and a Gated Rank Selector to dynamically balance stable long-term preferences and transient short-term interests. Experimental results on four public benchmark datasets show that our RecGRELA achieves state-of-the-art performance compared with existing SRSs based on Recurrent Neural Networks, Transformer, and Mamba while keeping low memory overhead.

Qiangqiang Wu, Grace McIlvain, Zhou Yu et al.

Foundation models (FMs) have shown great promise in medical imaging, but most FMs are trained on unimodal data within isolated domains, such as brain MRI alone. Human aging and disease arise through coordinated biological processes across organs, therefore motivating multimodal FMs that learn whole-body representations. A key challenge, however, is that real-world multimodal biomedical data are often missing not at random, which can reduce power, limit generalizability, and introduce bias. We propose Pan-FM, a pan-organ foundation model pre-trained on imaging from seven organs (Brain, Heart, Adipose, Liver, Kidney, Spleen, and Pancreas) under realistic missing-organ scenarios. Pan-FM uses a unified backbone that handles organ missingness during both training and inference, and is pre-trained with masking-based self-distillation. We find that naive multimodal pre-training leads to dominant-organ shortcut learning bias, with the model over-relying on dominant organs such as adipose and heart. To address this, we introduce Saliency-Guided Masking (SGM), which uses the model attention distribution to adaptively mask dominant organs during pre-training, thus encouraging more balanced cross-organ, whole-body learning. Notably, SGM introduces negligible computational overhead and can be seamlessly integrated into existing self-supervised learning frameworks to improve multi-organ representation learning. On the UK Biobank, Pan-FM achieves stronger prediction across 13 disease categories and 14 single disease entities than single-organ and multi-organ baselines, with improved robustness under missing-organ settings. Pan-FM serves as a scalable solution to realistic modality-missingness in multimodal learning in system neuroscience and as a step toward more generalizable whole-body FMs.

Kun Zeng, Yu Huo, Siyu Zhang et al.

Skill-augmented agents increasingly rely on large reusable skill libraries, but retrieving relevant skills is not the same as presenting usable context. Existing methods typically return atomic skills or dependency-aware bundles whose internal roles remain implicit, leaving the agent to infer the execution entry point, support skills, visible requirements, and failure-avoidance guidance. We introduce Group of Skills (GoSkills), an inference-time group-structured retrieval method that changes the agent-facing retrieval object from a flat skill list to a compact, role-labeled execution context. GoSkills builds anchor-centered skill groups from a typed skill graph, expands support groups through a group graph, bottlenecks the selected group plan into a bounded set of atomic skill payloads, and renders a fixed execution contract with Start, Support, Check, and Avoid fields, without changing the downstream agent, skill payloads, or execution environment. Experiments on SkillsBench and ALFWorld show that GoSkills preserves visible-requirement coverage under a small skill budget, improves over flat skill-access baselines, and often improves reward and agent-only runtime relative to structural retrieval references.

Junhao Wen, Mathilde Antoniades, Zhijian Yang et al.

Machine learning has been increasingly used to obtain individualized neuroimaging signatures for disease diagnosis, prognosis, and response to treatment in neuropsychiatric and neurodegenerative disorders. Therefore, it has contributed to a better understanding of disease heterogeneity by identifying disease subtypes that present significant differences in various brain phenotypic measures. In this review, we first present a systematic literature overview of studies using machine learning and multimodal MRI to unravel disease heterogeneity in various neuropsychiatric and neurodegenerative disorders, including Alzheimer disease, schizophrenia, major depressive disorder, autism spectrum disorder, multiple sclerosis, as well as their potential in transdiagnostic settings. Subsequently, we summarize relevant machine learning methodologies and discuss an emerging paradigm which we call dimensional neuroimaging endophenotype (DNE). DNE dissects the neurobiological heterogeneity of neuropsychiatric and neurodegenerative disorders into a low dimensional yet informative, quantitative brain phenotypic representation, serving as a robust intermediate phenotype (i.e., endophenotype) largely reflecting underlying genetics and etiology. Finally, we discuss the potential clinical implications of the current findings and envision future research avenues.

Junhao Wen, Erdem Varol, Zhijian Yang et al.

The imaging community has increasingly adopted machine learning (ML) methods to provide individualized imaging signatures related to disease diagnosis, prognosis, and response to treatment. Clinical neuroscience and cancer imaging have been two areas in which ML has offered particular promise. However, many neurologic and neuropsychiatric diseases, as well as cancer, are often heterogeneous in terms of their clinical manifestations, neuroanatomical patterns or genetic underpinnings. Therefore, in such cases, seeking a single disease signature might be ineffectual in delivering individualized precision diagnostics. The current chapter focuses on ML methods, especially semi-supervised clustering, that seek disease subtypes using imaging data. Work from Alzheimer Disease and its prodromal stages, psychosis, depression, autism, and brain cancer are discussed. Our goal is to provide the readers with a broad overview in terms of methodology and clinical applications.

Junhao Wen, Cynthia H. Y. Fu, Duygu Tosun et al.

Late-life depression (LLD) is characterized by considerable heterogeneity in clinical manifestation. Unraveling such heterogeneity would aid in elucidating etiological mechanisms and pave the road to precision and individualized medicine. We sought to delineate, cross-sectionally and longitudinally, disease-related heterogeneity in LLD linked to neuroanatomy, cognitive functioning, clinical symptomatology, and genetic profiles. Multimodal data from a multicentre sample (N=996) were analyzed. A semi-supervised clustering method (HYDRA) was applied to regional grey matter (GM) brain volumes to derive dimensional representations. Two dimensions were identified, which accounted for the LLD-related heterogeneity in voxel-wise GM maps, white matter (WM) fractional anisotropy (FA), neurocognitive functioning, clinical phenotype, and genetics. Dimension one (Dim1) demonstrated relatively preserved brain anatomy without WM disruptions relative to healthy controls. In contrast, dimension two (Dim2) showed widespread brain atrophy and WM integrity disruptions, along with cognitive impairment and higher depression severity. Moreover, one de novo independent genetic variant (rs13120336) was significantly associated with Dim 1 but not with Dim 2. Notably, the two dimensions demonstrated significant SNP-based heritability of 18-27% within the general population (N=12,518 in UKBB). Lastly, in a subset of individuals having longitudinal measurements, Dim2 demonstrated a more rapid longitudinal decrease in GM and brain age, and was more likely to progress to Alzheimers disease, compared to Dim1 (N=1,413 participants and 7,225 scans from ADNI, BLSA, and BIOCARD datasets).

Zhijian Yang, Ilya M. Nasrallah, Haochang Shou et al.

Heterogeneity of brain diseases is a challenge for precision diagnosis/prognosis. We describe and validate Smile-GAN (SeMI-supervised cLustEring-Generative Adversarial Network), a novel semi-supervised deep-clustering method, which dissects neuroanatomical heterogeneity, enabling identification of disease subtypes via their imaging signatures relative to controls. When applied to MRIs (2 studies; 2,832 participants; 8,146 scans) including cognitively normal individuals and those with cognitive impairment and dementia, Smile-GAN identified 4 neurodegenerative patterns/axes: P1, normal anatomy and highest cognitive performance; P2, mild/diffuse atrophy and more prominent executive dysfunction; P3, focal medial temporal atrophy and relatively greater memory impairment; P4, advanced neurodegeneration. Further application to longitudinal data revealed two distinct progression pathways: P1$\rightarrow$P2$\rightarrow$P4 and P1$\rightarrow$P3$\rightarrow$P4. Baseline expression of these patterns predicted the pathway and rate of future neurodegeneration. Pattern expression offered better yet complementary performance in predicting clinical progression, compared to amyloid/tau. These deep-learning derived biomarkers offer promise for precision diagnostics and targeted clinical trial recruitment.

Junhao Wen, Erdem Varol, Ganesh Chand et al.

There is a growing amount of clinical, anatomical and functional evidence for the heterogeneous presentation of neuropsychiatric and neurodegenerative diseases such as schizophrenia and Alzheimers Disease (AD). Elucidating distinct subtypes of diseases allows a better understanding of neuropathogenesis and enables the possibility of developing targeted treatment programs. Recent semi-supervised clustering techniques have provided a data-driven way to understand disease heterogeneity. However, existing methods do not take into account that subtypes of the disease might present themselves at different spatial scales across the brain. Here, we introduce a novel method, MAGIC, to uncover disease heterogeneity by leveraging multi-scale clustering. We first extract multi-scale patterns of structural covariance (PSCs) followed by a semi-supervised clustering with double cyclic block-wise optimization across different scales of PSCs. We validate MAGIC using simulated heterogeneous neuroanatomical data and demonstrate its clinical potential by exploring the heterogeneity of AD using T1 MRI scans of 228 cognitively normal (CN) and 191 patients. Our results indicate two main subtypes of AD with distinct atrophy patterns that consist of both fine-scale atrophy in the hippocampus as well as large-scale atrophy in cortical regions. The evidence for the heterogeneity is further corroborated by the clinical evaluation of two subtypes, which indicates that there is a subpopulation of AD patients that tend to be younger and decline faster in cognitive performance relative to the other subpopulation, which tends to be older and maintains a relatively steady decline in cognitive abilities.

Zhijian Yang, Junhao Wen, Christos Davatzikos

Machine learning methods applied to complex biomedical data has enabled the construction of disease signatures of diagnostic/prognostic value. However, less attention has been given to understanding disease heterogeneity. Semi-supervised clustering methods can address this problem by estimating multiple transformations from a (e.g. healthy) control (CN) group to a patient (PT) group, seeking to capture the heterogeneity of underlying pathlogic processes. Herein, we propose a novel method, Smile-GANs (SeMi-supervIsed cLustEring via GANs), for semi-supervised clustering, and apply it to brain MRI scans. Smile-GANs first learns multiple distinct mappings by generating PT from CN, with each mapping characterizing one relatively distinct pathological pattern. Moreover, a clustering model is trained interactively with mapping functions to assign PT into corresponding subtype memberships. Using relaxed assumptions on PT/CN data distribution and imposing mapping non-linearity, Smile-GANs captures heterogeneous differences in distribution between the CN and PT domains. We first validate Smile-GANs using simulated data, subsequently on real data, by demonstrating its potential in characterizing heterogeneity in Alzheimer's Disease (AD) and its prodromal phases. The model was first trained using baseline MRIs from the ADNI2 database and then applied to longitudinal data from ADNI1 and BLSA. Four robust subtypes with distinct neuroanatomical patterns were discovered: 1) normal brain, 2) diffuse atrophy atypical of AD, 3) focal medial temporal lobe atrophy, 4) typical-AD. Further longitudinal analyses discover two distinct progressive pathways from prodromal to full AD: i) subtypes 1 - 2 - 4, and ii) subtypes 1 - 3 - 4. Although demonstrated on an important biomedical problem, Smile-GANs is general and can find application in many biomedical and other domains.

Min Gao, Junwei Zhang, Junliang Yu et al.

Recommender systems (RSs) now play a very important role in the online lives of people as they serve as personalized filters for users to find relevant items from an array of options. Owing to their effectiveness, RSs have been widely employed in consumer-oriented e-commerce platforms. However, despite their empirical successes, these systems still suffer from two limitations: data noise and data sparsity. In recent years, generative adversarial networks (GANs) have garnered increased interest in many fields, owing to their strong capacity to learn complex real data distributions; their abilities to enhance RSs by tackling the challenges these systems exhibit have also been demonstrated in numerous studies. In general, two lines of research have been conducted, and their common ideas can be summarized as follows: (1) for the data noise issue, adversarial perturbations and adversarial sampling-based training often serve as a solution; (2) for the data sparsity issue, data augmentation--implemented by capturing the distribution of real data under the minimax framework--is the primary coping strategy. To gain a comprehensive understanding of these research efforts, we review the corresponding studies and models, organizing them from a problem-driven perspective. More specifically, we propose a taxonomy of these models, along with their detailed descriptions and advantages. Finally, we elaborate on several open issues and current trends in GAN-based RSs.

Qilin Fan, Xiuhua Li, Jian Li et al.

As ubiquitous and personalized services are growing boomingly, an increasingly large amount of traffic is generated over the network by massive mobile devices. As a result, content caching is gradually extending to network edges to provide low-latency services, improve quality of service, and reduce redundant data traffic. Compared to the conventional content delivery networks, caches in edge networks with smaller sizes usually have to accommodate more bursty requests. In this paper, we propose an evolving learning-based content caching policy, named PA-Cache in edge networks. It adaptively learns time-varying content popularity and determines which contents should be replaced when the cache is full. Unlike conventional deep neural networks (DNNs), which learn a fine-tuned but possibly outdated or biased prediction model using the entire training dataset with high computational complexity, PA-Cache weighs a large set of content features and trains the multi-layer recurrent neural network from shallow to deeper when more requests arrive over time. We extensively evaluate the performance of our proposed PA-Cache on real-world traces from a large online video-on-demand service provider. \rb{The results show that PA-Cache outperforms existing popular caching algorithms and approximates the optimal algorithm with only a 3.8\% performance gap when the cache percentage is 1.0\%}. PA-Cache also significantly reduces the computational cost compared to conventional DNN-based approaches.

Jorge Samper-González, Ninon Burgos, Simona Bottani et al.

A large number of papers have introduced novel machine learning and feature extraction methods for automatic classification of AD. However, they are difficult to reproduce because key components of the validation are often not readily available. These components include selected participants and input data, image preprocessing and cross-validation procedures. The performance of the different approaches is also difficult to compare objectively. In particular, it is often difficult to assess which part of the method provides a real improvement, if any. We propose a framework for reproducible and objective classification experiments in AD using three publicly available datasets (ADNI, AIBL and OASIS). The framework comprises: i) automatic conversion of the three datasets into BIDS format, ii) a modular set of preprocessing pipelines, feature extraction and classification methods, together with an evaluation framework, that provide a baseline for benchmarking the different components. We demonstrate the use of the framework for a large-scale evaluation on 1960 participants using T1 MRI and FDG PET data. In this evaluation, we assess the influence of different modalities, preprocessing, feature types, classifiers, training set sizes and datasets. Performances were in line with the state-of-the-art. FDG PET outperformed T1 MRI for all classification tasks. No difference in performance was found for the use of different atlases, image smoothing, partial volume correction of FDG PET images, or feature type. Linear SVM and L2-logistic regression resulted in similar performance and both outperformed random forests. The classification performance increased along with the number of subjects used for training. Classifiers trained on ADNI generalized well to AIBL and OASIS. All the code of the framework and the experiments is publicly available at: https://gitlab.icm-institute.org/aramislab/AD-ML.

Pengdeng Li, Lu-Xing Yang, Xiaofan Yang et al.

The new cyber attack pattern of advanced persistent threat (APT) has posed a serious threat to modern society. This paper addresses the APT defense problem, i.e., the problem of how to effectively defend against an APT campaign. Based on a novel APT attack-defense model, the effectiveness of an APT defense strategy is quantified. Thereby, the APT defense problem is modeled as an optimal control problem, in which an optimal control stands for a most effective APT defense strategy. The existence of an optimal control is proved, and an optimality system is derived. Consequently, an optimal control can be figured out by solving the optimality system. Some examples of the optimal control are given. Finally, the influence of some factors on the effectiveness of an optimal control is examined through computer experiments. These findings help organizations to work out policies of defending against APTs.