Fei Wang

Matthew Brendel, Chang Su, Zilong Bai et al.

Single-cell RNA-sequencing (scRNA-seq) has become a routinely used technique to quantify the gene expression profile of thousands of single cells simultaneously. Analysis of scRNA-seq data plays an important role in the study of cell states and phenotypes, and has helped elucidate biological processes, such as those occurring during development of complex organisms and improved our understanding of disease states, such as cancer, diabetes, and COVID, among others. Deep learning, a recent advance of artificial intelligence that has been used to address many problems involving large datasets, has also emerged as a promising tool for scRNA-seq data analysis, as it has a capacity to extract informative, compact features from noisy, heterogeneous, and high-dimensional scRNA-seq data to improve downstream analysis. The present review aims at surveying recently developed deep learning techniques in scRNA-seq data analysis, identifying key steps within the scRNA-seq data analysis pipeline that have been advanced by deep learning, and explaining the benefits of deep learning over more conventional analysis tools. Finally, we summarize the challenges in current deep learning approaches faced within scRNA-seq data and discuss potential directions for improvements in deep algorithms for scRNA-seq data analysis.

Zhaoyi Sun, Mingquan Lin, Qingqing Zhu et al. · uw

Computer-assisted diagnostic and prognostic systems of the future should be capable of simultaneously processing multimodal data. Multimodal deep learning (MDL), which involves the integration of multiple sources of data, such as images and text, has the potential to revolutionize the analysis and interpretation of biomedical data. However, it only caught researchers' attention recently. To this end, there is a critical need to conduct a systematic review on this topic, identify the limitations of current work, and explore future directions. In this scoping review, we aim to provide a comprehensive overview of the current state of the field and identify key concepts, types of studies, and research gaps with a focus on biomedical images and texts joint learning, mainly because these two were the most commonly available data types in MDL research. This study reviewed the current uses of multimodal deep learning on five tasks: (1) Report generation, (2) Visual question answering, (3) Cross-modal retrieval, (4) Computer-aided diagnosis, and (5) Semantic segmentation. Our results highlight the diverse applications and potential of MDL and suggest directions for future research in the field. We hope our review will facilitate the collaboration of natural language processing (NLP) and medical imaging communities and support the next generation of decision-making and computer-assisted diagnostic system development.

Hyunsik Yoo, Zhichen Zeng, Jian Kang et al.

User-side group fairness is crucial for modern recommender systems, aiming to alleviate performance disparities among user groups defined by sensitive attributes like gender, race, or age. In the ever-evolving landscape of user-item interactions, continual adaptation to newly collected data is crucial for recommender systems to stay aligned with the latest user preferences. However, we observe that such continual adaptation often exacerbates performance disparities. This necessitates a thorough investigation into user-side fairness in dynamic recommender systems, an area that has been unexplored in the literature. This problem is challenging due to distribution shifts, frequent model updates, and non-differentiability of ranking metrics. To our knowledge, this paper presents the first principled study on ensuring user-side fairness in dynamic recommender systems. We start with theoretical analyses on fine-tuning v.s. retraining, showing that the best practice is incremental fine-tuning with restart. Guided by our theoretical analyses, we propose FAir Dynamic rEcommender (FADE), an end-to-end fine-tuning framework to dynamically ensure user-side fairness over time. To overcome the non-differentiability of recommendation metrics in the fairness loss, we further introduce Differentiable Hit (DH) as an improvement over the recent NeuralNDCG method, not only alleviating its gradient vanishing issue but also achieving higher efficiency. Besides that, we also address the instability issue of the fairness loss by leveraging the competing nature between the recommendation loss and the fairness loss. Through extensive experiments on real-world datasets, we demonstrate that FADE effectively and efficiently reduces performance disparities with little sacrifice in the overall recommendation performance.

Adrienne Kline, Hanyin Wang, Yikuan Li et al.

As machine learning and artificial intelligence are more frequently being leveraged to tackle problems in the health sector, there has been increased interest in utilizing them in clinical decision-support. This has historically been the case in single modal data such as electronic health record data. Attempts to improve prediction and resemble the multimodal nature of clinical expert decision-making this has been met in the computational field of machine learning by a fusion of disparate data. This review was conducted to summarize this field and identify topics ripe for future research. We conducted this review in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) extension for Scoping Reviews to characterize multi-modal data fusion in health. We used a combination of content analysis and literature searches to establish search strings and databases of PubMed, Google Scholar, and IEEEXplore from 2011 to 2021. A final set of 125 articles were included in the analysis. The most common health areas utilizing multi-modal methods were neurology and oncology. However, there exist a wide breadth of current applications. The most common form of information fusion was early fusion. Notably, there was an improvement in predictive performance performing heterogeneous data fusion. Lacking from the papers were clear clinical deployment strategies and pursuit of FDA-approved tools. These findings provide a map of the current literature on multimodal data fusion as applied to health diagnosis/prognosis problems. Multi-modal machine learning, while more robust in its estimations over unimodal methods, has drawbacks in its scalability and the time-consuming nature of information concatenation.

Jianmin Chen, Robert H. Aseltine, Fei Wang et al.

Statistical learning with a large number of rare binary features is commonly encountered in analyzing electronic health records (EHR) data, especially in the modeling of disease onset with prior medical diagnoses and procedures. Dealing with the resulting highly sparse and large-scale binary feature matrix is notoriously challenging as conventional methods may suffer from a lack of power in testing and inconsistency in model fitting while machine learning methods may suffer from the inability of producing interpretable results or clinically-meaningful risk factors. To improve EHR-based modeling and utilize the natural hierarchical structure of disease classification, we propose a tree-guided feature selection and logic aggregation approach for large-scale regression with rare binary features, in which dimension reduction is achieved through not only a sparsity pursuit but also an aggregation promoter with the logic operator of ``or''. We convert the combinatorial problem into a convex linearly-constrained regularized estimation, which enables scalable computation with theoretical guarantees. In a suicide risk study with EHR data, our approach is able to select and aggregate prior mental health diagnoses as guided by the diagnosis hierarchy of the International Classification of Diseases. By balancing the rarity and specificity of the EHR diagnosis records, our strategy improves both prediction and model interpretation. We identify important higher-level categories and subcategories of mental health conditions and simultaneously determine the level of specificity needed for each of them in predicting suicide risk.

Hejie Cui, Jiaying Lu, Ran Xu et al.

This comprehensive review aims to provide an overview of the current state of Healthcare Knowledge Graphs (HKGs), including their construction, utilization models, and applications across various healthcare and biomedical research domains. We thoroughly analyzed existing literature on HKGs, covering their construction methodologies, utilization techniques, and applications in basic science research, pharmaceutical research and development, clinical decision support, and public health. The review encompasses both model-free and model-based utilization approaches and the integration of HKGs with large language models (LLMs). We searched Google Scholar for relevant papers on HKGs and classified them into the following topics: HKG construction, HKG utilization, and their downstream applications in various domains. We also discussed their special challenges and the promise for future work. The review highlights the potential of HKGs to significantly impact biomedical research and clinical practice by integrating vast amounts of biomedical knowledge from multiple domains. The synergy between HKGs and LLMs offers promising opportunities for constructing more comprehensive knowledge graphs and improving the accuracy of healthcare applications. HKGs have emerged as a powerful tool for structuring medical knowledge, with broad applications across biomedical research, clinical decision-making, and public health. This survey serves as a roadmap for future research and development in the field of HKGs, highlighting the potential of combining knowledge graphs with advanced machine learning models for healthcare transformation.

Yingsong Huang, Bing Bai, Shengwei Zhao et al.

Learning against label noise is a vital topic to guarantee a reliable performance for deep neural networks. Recent research usually refers to dynamic noise modeling with model output probabilities and loss values, and then separates clean and noisy samples. These methods have gained notable success. However, unlike cherry-picked data, existing approaches often cannot perform well when facing imbalanced datasets, a common scenario in the real world. We thoroughly investigate this phenomenon and point out two major issues that hinder the performance, i.e., \emph{inter-class loss distribution discrepancy} and \emph{misleading predictions due to uncertainty}. The first issue is that existing methods often perform class-agnostic noise modeling. However, loss distributions show a significant discrepancy among classes under class imbalance, and class-agnostic noise modeling can easily get confused with noisy samples and samples in minority classes. The second issue refers to that models may output misleading predictions due to epistemic uncertainty and aleatoric uncertainty, thus existing methods that rely solely on the output probabilities may fail to distinguish confident samples. Inspired by our observations, we propose an Uncertainty-aware Label Correction framework~(ULC) to handle label noise on imbalanced datasets. First, we perform epistemic uncertainty-aware class-specific noise modeling to identify trustworthy clean samples and refine/discard highly confident true/corrupted labels. Then, we introduce aleatoric uncertainty in the subsequent learning process to prevent noise accumulation in the label noise modeling process. We conduct experiments on several synthetic and real-world datasets. The results demonstrate the effectiveness of the proposed method, especially on imbalanced datasets.

Jacqueline R. M. A. Maasch, Hao Zhang, Qian Yang et al.

The cost of manual data labeling can be a significant obstacle in supervised learning. Data programming (DP) offers a weakly supervised solution for training dataset creation, wherein the outputs of user-defined programmatic labeling functions (LFs) are reconciled through unsupervised learning. However, DP can fail to outperform an unweighted majority vote in some scenarios, including low-data contexts. This work introduces a Bayesian extension of classical DP that mitigates failures of unsupervised learning by augmenting the DP objective with regularization terms. Regularized learning is achieved through maximum a posteriori estimation with informative priors. Majority vote is proposed as a proxy signal for automated prior parameter selection. Results suggest that regularized DP improves performance relative to maximum likelihood and majority voting, confers greater interpretability, and bolsters performance in low-data regimes.

Mingxuan Liu, Yilin Ning, Salinelat Teixayavong et al.

Artificial intelligence (AI) has demonstrated the ability to extract insights from data, but the issue of fairness remains a concern in high-stakes fields such as healthcare. Despite extensive discussion and efforts in algorithm development, AI fairness and clinical concerns have not been adequately addressed. In this paper, we discuss the misalignment between technical and clinical perspectives of AI fairness, highlight the barriers to AI fairness' translation to healthcare, advocate multidisciplinary collaboration to bridge the knowledge gap, and provide possible solutions to address the clinical concerns pertaining to AI fairness.

Mingquan Lin, Song Wang, Ying Ding et al.

Background: The predictive Intensive Care Unit (ICU) scoring system plays an important role in ICU management because it predicts important outcomes, especially mortality. Many scoring systems have been developed and used in the ICU. These scoring systems are primarily based on the structured clinical data in the electronic health record (EHR), which may suffer the loss of important clinical information in the narratives and images. Methods: In this work, we build a deep learning based survival prediction model with multi-modality data to predict ICU mortality. Four sets of features are investigated: (1) physiological measurements of Simplified Acute Physiology Score (SAPS) II, (2) common thorax diseases pre-defined by radiologists, (3) BERT-based text representations, and (4) chest X-ray image features. We use the Medical Information Mart for Intensive Care IV (MIMIC-IV) dataset to evaluate the proposed model. Results: Our model achieves the average C-index of 0.7829 (95% confidence interval, 0.7620-0.8038), which substantially exceeds that of the baseline with SAPS-II features (0.7470 (0.7263-0.7676)). Ablation studies further demonstrate the contributions of pre-defined labels (2.00%), text features (2.44%), and image features (2.82%).

Mingquan Lin, Yuyun Xiao, Bojian Hou et al.

In the United States, primary open-angle glaucoma (POAG) is the leading cause of blindness, especially among African American and Hispanic individuals. Deep learning has been widely used to detect POAG using fundus images as its performance is comparable to or even surpasses diagnosis by clinicians. However, human bias in clinical diagnosis may be reflected and amplified in the widely-used deep learning models, thus impacting their performance. Biases may cause (1) underdiagnosis, increasing the risks of delayed or inadequate treatment, and (2) overdiagnosis, which may increase individuals' stress, fear, well-being, and unnecessary/costly treatment. In this study, we examined the underdiagnosis and overdiagnosis when applying deep learning in POAG detection based on the Ocular Hypertension Treatment Study (OHTS) from 22 centers across 16 states in the United States. Our results show that the widely-used deep learning model can underdiagnose or overdiagnose underserved populations. The most underdiagnosed group is female younger (< 60 yrs) group, and the most overdiagnosed group is Black older (>=60 yrs) group. Biased diagnosis through traditional deep learning methods may delay disease detection, treatment and create burdens among under-served populations, thereby, raising ethical concerns about using deep learning models in ophthalmology clinics.

Fei Wang, Xuecheng Wu, Zheng Zhang et al.

The powerful generative capabilities of diffusion models have significantly advanced the field of image synthesis, enhancing both full image generation and inpainting-based image editing. Despite their remarkable advancements, diffusion models also raise concerns about potential misuse for malicious purposes. However, existing approaches struggle to identify images generated by diffusion-based inpainting models, even when similar inpainted images are included in their training data. To address this challenge, we propose a novel detection method based on End-to-end denoising diffusion (End4). Specifically, End4 designs a denoising reconstruction model to improve the alignment degree between the latent spaces of the reconstruction and detection processes, thus reconstructing features that are more conducive to detection. Meanwhile, it leverages a Scale-aware Pyramid-like Fusion Module (SPFM) that refines local image features under the guidance of attention pyramid layers at different scales, enhancing feature discriminability. Additionally, to evaluate detection performance on inpainted images, we establish a comprehensive benchmark comprising images generated from five distinct masked regions. Extensive experiments demonstrate that our End4 effectively generalizes to unseen masking patterns and remains robust under various perturbations. Our code and dataset will be released soon.

Zheng Yuan, Zhengyun Zhao, Haixia Sun et al.

This paper proposes CODER: contrastive learning on knowledge graphs for cross-lingual medical term representation. CODER is designed for medical term normalization by providing close vector representations for different terms that represent the same or similar medical concepts with cross-lingual support. We train CODER via contrastive learning on a medical knowledge graph (KG) named the Unified Medical Language System, where similarities are calculated utilizing both terms and relation triplets from KG. Training with relations injects medical knowledge into embeddings and aims to provide potentially better machine learning features. We evaluate CODER in zero-shot term normalization, semantic similarity, and relation classification benchmarks, which show that CODERoutperforms various state-of-the-art biomedical word embedding, concept embeddings, and contextual embeddings. Our codes and models are available at https://github.com/GanjinZero/CODER.

Jian Liang, Bing Bai, Yuren Cao et al.

Model interpretation is essential in data mining and knowledge discovery. It can help understand the intrinsic model working mechanism and check if the model has undesired characteristics. A popular way of performing model interpretation is Instance-wise Feature Selection (IFS), which provides an importance score of each feature representing the data samples to explain how the model generates the specific output. In this paper, we propose a Model-agnostic Effective Efficient Direct (MEED) IFS framework for model interpretation, mitigating concerns about sanity, combinatorial shortcuts, model identifiability, and information transmission. Also, we focus on the following setting: using selected features to directly predict the output of the given model, which serves as a primary evaluation metric for model-interpretation methods. Apart from the features, we involve the output of the given model as an additional input to learn an explainer based on more accurate information. To learn the explainer, besides fidelity, we propose an Adversarial Infidelity Learning (AIL) mechanism to boost the explanation learning by screening relatively unimportant features. Through theoretical and experimental analysis, we show that our AIL mechanism can help learn the desired conditional distribution between selected features and targets. Moreover, we extend our framework by integrating efficient interpretation methods as proper priors to provide a warm start. Comprehensive empirical evaluation results are provided by quantitative metrics and human evaluation to demonstrate the effectiveness and superiority of our proposed method. Our code is publicly available online at https://github.com/langlrsw/MEED.

Tianyang Liu, Fei Wang, Muhao Chen

Large Language Models (LLMs) have shown to be capable of various tasks, yet their capability in interpreting and reasoning over tabular data remains an underexplored area. In this context, this study investigates from three core perspectives: the robustness of LLMs to structural perturbations in tables, the comparative analysis of textual and symbolic reasoning on tables, and the potential of boosting model performance through the aggregation of multiple reasoning pathways. We discover that structural variance of tables presenting the same content reveals a notable performance decline, particularly in symbolic reasoning tasks. This prompts the proposal of a method for table structure normalization. Moreover, textual reasoning slightly edges out symbolic reasoning, and a detailed error analysis reveals that each exhibits different strengths depending on the specific tasks. Notably, the aggregation of textual and symbolic reasoning pathways, bolstered by a mix self-consistency mechanism, resulted in achieving SOTA performance, with an accuracy of 73.6% on WIKITABLEQUESTIONS, representing a substantial advancement over previous existing table processing paradigms of LLMs.

Adamo Young, Fei Wang, David S Wishart et al.

Compound identification from tandem mass spectrometry (MS/MS) data is a critical step in the analysis of complex mixtures. Typical solutions for the MS/MS spectrum to compound (MS2C) problem involve comparing the unknown spectrum against a library of known spectrum-molecule pairs, an approach that is limited by incomplete library coverage. Compound to MS/MS spectrum (C2MS) models can improve retrieval rates by augmenting real libraries with predicted MS/MS spectra. Unfortunately, many existing C2MS models suffer from problems with mass accuracy, generalization, or interpretability. We develop a new probabilistic method for C2MS prediction, FraGNNet, that can efficiently and accurately simulate MS/MS spectra with high mass accuracy. Our approach formulates the C2MS problem as learning a distribution over molecule fragments. FraGNNet achieves state-of-the-art performance in terms of prediction error and surpasses existing C2MS models as a tool for retrieval-based MS2C.

Xingbo Wang, Janessa Griffith, Daniel A. Adler et al.

Despite the prevalence of sleep-tracking devices, many individuals struggle to translate data into actionable improvements in sleep health. Current methods often provide data-driven suggestions but may not be feasible and adaptive to real-life constraints and individual contexts. We present HealthGuru, a novel large language model-powered chatbot to enhance sleep health through data-driven, theory-guided, and adaptive recommendations with conversational behavior change support. HealthGuru's multi-agent framework integrates wearable device data, contextual information, and a contextual multi-armed bandit model to suggest tailored sleep-enhancing activities. The system facilitates natural conversations while incorporating data-driven insights and theoretical behavior change techniques. Our eight-week in-the-wild deployment study with 16 participants compared HealthGuru to a baseline chatbot. Results show improved metrics like sleep duration and activity scores, higher quality responses, and increased user motivation for behavior change with HealthGuru. We also identify challenges and design considerations for personalization and user engagement in health chatbots.

Pengfei Hu, Xiaoxue Han, Fei Wang et al.

Healthcare providers often divide patient populations into cohorts based on shared clinical factors, such as medical history, to deliver personalized healthcare services. This idea has also been adopted in clinical prediction models, where it presents a vital challenge: capturing both global and cohort-specific patterns while enabling model generalization to unseen domains. Addressing this challenge falls under the scope of domain generalization (DG). However, conventional DG approaches often struggle in clinical settings due to the absence of explicit domain labels and the inherent gap in medical knowledge. To address this, we propose UdonCare, a hierarchy-guided method that iteratively divides patients into latent domains and decomposes domain-invariant (label) information from patient data. Our method identifies patient domains by pruning medical ontologies (e.g. ICD-9-CM hierarchy). On two public datasets, MIMIC-III and MIMIC-IV, UdonCare shows superiority over eight baselines across four clinical prediction tasks with substantial domain gaps, highlighting the untapped potential of medical knowledge in guiding clinical domain generalization problems.

Haoyang Li, Jie Xu, Kyra Gan et al.

Federated causal inference enables multi-site treatment effect estimation without sharing individual-level data, offering a privacy-preserving solution for real-world evidence generation. However, data heterogeneity across sites, manifested in differences in covariate, treatment, and outcome, poses significant challenges for unbiased and efficient estimation. In this paper, we present a comprehensive review and theoretical analysis of federated causal effect estimation across both binary/continuous and time-to-event outcomes. We classify existing methods into weight-based strategies and optimization-based frameworks and further discuss extensions including personalized models, peer-to-peer communication, and model decomposition. For time-to-event outcomes, we examine federated Cox and Aalen-Johansen models, deriving asymptotic bias and variance under heterogeneity. Our analysis reveals that FedProx-style regularization achieves near-optimal bias-variance trade-offs compared to naive averaging and meta-analysis. We review related software tools and conclude by outlining opportunities, challenges, and future directions for scalable, fair, and trustworthy federated causal inference in distributed healthcare systems.

Chunyu Wei, Wenji Hu, Xingjia Hao et al.

Graph anomaly detection faces significant challenges due to the scarcity of reliable anomaly-labeled datasets, driving the development of unsupervised methods. Graph autoencoders (GAEs) have emerged as a dominant approach by reconstructing graph structures and node features while deriving anomaly scores from reconstruction errors. However, relying solely on reconstruction error for anomaly detection has limitations, as it increases the sensitivity to noise and overfitting. To address these issues, we propose Graph Evidential Learning (GEL), a probabilistic framework that redefines the reconstruction process through evidential learning. By modeling node features and graph topology using evidential distributions, GEL quantifies two types of uncertainty: graph uncertainty and reconstruction uncertainty, incorporating them into the anomaly scoring mechanism. Extensive experiments demonstrate that GEL achieves state-of-the-art performance while maintaining high robustness against noise and structural perturbations.

Gregory Holste, Mingquan Lin, Ruiwen Zhou et al.

Deep learning has enabled breakthroughs in automated diagnosis from medical imaging, with many successful applications in ophthalmology. However, standard medical image classification approaches only assess disease presence at the time of acquisition, neglecting the common clinical setting of longitudinal imaging. For slow, progressive eye diseases like age-related macular degeneration (AMD) and primary open-angle glaucoma (POAG), patients undergo repeated imaging over time to track disease progression and forecasting the future risk of developing disease is critical to properly plan treatment. Our proposed Longitudinal Transformer for Survival Analysis (LTSA) enables dynamic disease prognosis from longitudinal medical imaging, modeling the time to disease from sequences of fundus photography images captured over long, irregular time periods. Using longitudinal imaging data from the Age-Related Eye Disease Study (AREDS) and Ocular Hypertension Treatment Study (OHTS), LTSA significantly outperformed a single-image baseline in 19/20 head-to-head comparisons on late AMD prognosis and 18/20 comparisons on POAG prognosis. A temporal attention analysis also suggested that, while the most recent image is typically the most influential, prior imaging still provides additional prognostic value.

Suraj Rajendran, Weishen Pan, Mert R. Sabuncu et al.

Machine learning (ML) in healthcare presents numerous opportunities for enhancing patient care, population health, and healthcare providers' workflows. However, the real-world clinical and cost benefits remain limited due to challenges in data privacy, heterogeneous data sources, and the inability to fully leverage multiple data modalities. In this perspective paper, we introduce "patchwork learning" (PL), a novel paradigm that addresses these limitations by integrating information from disparate datasets composed of different data modalities (e.g., clinical free-text, medical images, omics) and distributed across separate and secure sites. PL allows the simultaneous utilization of complementary data sources while preserving data privacy, enabling the development of more holistic and generalizable ML models. We present the concept of patchwork learning and its current implementations in healthcare, exploring the potential opportunities and applicable data sources for addressing various healthcare challenges. PL leverages bridging modalities or overlapping feature spaces across sites to facilitate information sharing and impute missing data, thereby addressing related prediction tasks. We discuss the challenges associated with PL, many of which are shared by federated and multimodal learning, and provide recommendations for future research in this field. By offering a more comprehensive approach to healthcare data integration, patchwork learning has the potential to revolutionize the clinical applicability of ML models. This paradigm promises to strike a balance between personalization and generalizability, ultimately enhancing patient experiences, improving population health, and optimizing healthcare providers' workflows.

Dayang Wang, Fenglei Fan, Zhan Wu et al.

Low-dose computed tomography (LDCT) denoising is an important problem in CT research. Compared to the normal dose CT (NDCT), LDCT images are subjected to severe noise and artifacts. Recently in many studies, vision transformers have shown superior feature representation ability over convolutional neural networks (CNNs). However, unlike CNNs, the potential of vision transformers in LDCT denoising was little explored so far. To fill this gap, we propose a Convolution-free Token2Token Dilated Vision Transformer for low-dose CT denoising. The CTformer uses a more powerful token rearrangement to encompass local contextual information and thus avoids convolution. It also dilates and shifts feature maps to capture longer-range interaction. We interpret the CTformer by statically inspecting patterns of its internal attention maps and dynamically tracing the hierarchical attention flow with an explanatory graph. Furthermore, an overlapped inference mechanism is introduced to effectively eliminate the boundary artifacts that are common for encoder-decoder-based denoising models. Experimental results on Mayo LDCT dataset suggest that the CTformer outperforms the state-of-the-art denoising methods with a low computation overhead.

Qiyuan An, Ruijiang Li, Lin Gu et al.

Unsupervised domain adaptation (UDA) generally aligns the unlabeled target domain data to the distribution of the source domain to mitigate the distribution shift problem. The standard UDA requires sharing the source data with the target, having potential data privacy leaking risks. To protect the source data's privacy, we first propose to share the source feature distribution instead of the source data. However, sharing only the source feature distribution may still suffer from the membership inference attack who can infer an individual's membership by the black-box access to the source model. To resolve this privacy issue, we further study the under-explored problem of privacy-preserving domain adaptation and propose a method with a novel differential privacy training strategy to protect the source data privacy. We model the source feature distribution by Gaussian Mixture Models (GMMs) under the differential privacy setting and send it to the target client for adaptation. The target client resamples differentially private source features from GMMs and adapts on target data with several state-of-art UDA backbones. With our proposed method, the source data provider could avoid leaking source data privacy during domain adaptation as well as reserve the utility. To evaluate our proposed method's utility and privacy loss, we apply our model on a medical report disease label classification task using two noisy challenging clinical text datasets. The results show that our proposed method can preserve source data's privacy with a minor performance influence on the text classification task.

Bojian Hou, Hao Zhang, Gur Ladizhinsky et al.

Abstruse learning algorithms and complex datasets increasingly characterize modern clinical decision support systems (CDSS). As a result, clinicians cannot easily or rapidly scrutinize the CDSS recommendation when facing a difficult diagnosis or treatment decision in practice. Over-trust or under-trust are frequent. Prior research has explored supporting such assessments by explaining DST data inputs and algorithmic mechanisms. This paper explores a different approach: Providing precisely relevant, scientific evidence from biomedical literature. We present a proof-of-concept system, Clinical Evidence Engine, to demonstrate the technical and design feasibility of this approach across three domains (cardiovascular diseases, autism, cancer). Leveraging Clinical BioBERT, the system can effectively identify clinical trial reports based on lengthy clinical questions (e.g., "risks of catheter infection among adult patients in intensive care unit who require arterial catheters, if treated with povidone iodine-alcohol"). This capability enables the system to identify clinical trials relevant to diagnostic/treatment hypotheses -- a clinician's or a CDSS's. Further, Clinical Evidence Engine can identify key parts of a clinical trial abstract, including patient population (e.g., adult patients in intensive care unit who require arterial catheters), intervention (povidone iodine-alcohol), and outcome (risks of catheter infection). This capability opens up the possibility of enabling clinicians to 1) rapidly determine the match between a clinical trial and a clinical question, and 2) understand the result and contexts of the trial without extensive reading. We demonstrate this potential by illustrating two example use scenarios of the system. We discuss the idea of designing DST explanations not as specific to a DST or an algorithm, but as a domain-agnostic decision support infrastructure.

Weishen Pan, Sen Cui, Jiang Bian et al.

Algorithmic fairness has aroused considerable interests in data mining and machine learning communities recently. So far the existing research has been mostly focusing on the development of quantitative metrics to measure algorithm disparities across different protected groups, and approaches for adjusting the algorithm output to reduce such disparities. In this paper, we propose to study the problem of identification of the source of model disparities. Unlike existing interpretation methods which typically learn feature importance, we consider the causal relationships among feature variables and propose a novel framework to decompose the disparity into the sum of contributions from fairness-aware causal paths, which are paths linking the sensitive attribute and the final predictions, on the graph. We also consider the scenario when the directions on certain edges within those paths cannot be determined. Our framework is also model agnostic and applicable to a variety of quantitative disparity measures. Empirical evaluations on both synthetic and real-world data sets are provided to show that our method can provide precise and comprehensive explanations to the model disparities.

Tingyi Wanyan, Hossein Honarvar, Suraj K. Jaladanki et al.

Machine Learning (ML) models typically require large-scale, balanced training data to be robust, generalizable, and effective in the context of healthcare. This has been a major issue for developing ML models for the coronavirus-disease 2019 (COVID-19) pandemic where data is highly imbalanced, particularly within electronic health records (EHR) research. Conventional approaches in ML use cross-entropy loss (CEL) that often suffers from poor margin classification. For the first time, we show that contrastive loss (CL) improves the performance of CEL especially for imbalanced EHR data and the related COVID-19 analyses. This study has been approved by the Institutional Review Board at the Icahn School of Medicine at Mount Sinai. We use EHR data from five hospitals within the Mount Sinai Health System (MSHS) to predict mortality, intubation, and intensive care unit (ICU) transfer in hospitalized COVID-19 patients over 24 and 48 hour time windows. We train two sequential architectures (RNN and RETAIN) using two loss functions (CEL and CL). Models are tested on full sample data set which contain all available data and restricted data set to emulate higher class imbalance.CL models consistently outperform CEL models with the restricted data set on these tasks with differences ranging from 0.04 to 0.15 for AUPRC and 0.05 to 0.1 for AUROC. For the restricted sample, only the CL model maintains proper clustering and is able to identify important features, such as pulse oximetry. CL outperforms CEL in instances of severe class imbalance, on three EHR outcomes with respect to three performance metrics: predictive power, clustering, and feature importance. We believe that the developed CL framework can be expanded and used for EHR ML work in general.

Jian Liang, Yuren Cao, Shuang Li et al.

Authentication is the task of confirming the matching relationship between a data instance and a given identity. Typical examples of authentication problems include face recognition and person re-identification. Data-driven authentication could be affected by undesired biases, i.e., the models are often trained in one domain (e.g., for people wearing spring outfits) while applied in other domains (e.g., they change the clothes to summer outfits). Previous works have made efforts to eliminate domain-difference. They typically assume domain annotations are provided, and all the domains share classes. However, for authentication, there could be a large number of domains shared by different identities/classes, and it is impossible to annotate these domains exhaustively. It could make domain-difference challenging to model and eliminate. In this paper, we propose a domain-agnostic method that eliminates domain-difference without domain labels. We alternately perform latent domain discovery and domain-difference elimination until our model no longer detects domain-difference. In our approach, the latent domains are discovered by learning the heterogeneous predictive relationships between inputs and outputs. Then domain-difference is eliminated in both class-dependent and class-independent spaces to improve robustness of elimination. We further extend our method to a meta-learning framework to pursue more thorough domain-difference elimination. Comprehensive empirical evaluation results are provided to demonstrate the effectiveness and superiority of our proposed method.

Yuqi Si, Jingcheng Du, Zhao Li et al.

Patient representation learning refers to learning a dense mathematical representation of a patient that encodes meaningful information from Electronic Health Records (EHRs). This is generally performed using advanced deep learning methods. This study presents a systematic review of this field and provides both qualitative and quantitative analyses from a methodological perspective. We identified studies developing patient representations from EHRs with deep learning methods from MEDLINE, EMBASE, Scopus, the Association for Computing Machinery (ACM) Digital Library, and Institute of Electrical and Electronics Engineers (IEEE) Xplore Digital Library. After screening 363 articles, 49 papers were included for a comprehensive data collection. We noticed a typical workflow starting with feeding raw data, applying deep learning models, and ending with clinical outcome predictions as evaluations of the learned representations. Specifically, learning representations from structured EHR data was dominant (37 out of 49 studies). Recurrent Neural Networks were widely applied as the deep learning architecture (LSTM: 13 studies, GRU: 11 studies). Disease prediction was the most common application and evaluation (31 studies). Benchmark datasets were mostly unavailable (28 studies) due to privacy concerns of EHR data, and code availability was assured in 20 studies. We show the importance and feasibility of learning comprehensive representations of patient EHR data through a systematic review. Advances in patient representation learning techniques will be essential for powering patient-level EHR analyses. Future work will still be devoted to leveraging the richness and potential of available EHR data. Knowledge distillation and advanced learning techniques will be exploited to assist the capability of learning patient representation further.

Prithwish Chakraborty, Fei Wang, Jianying Hu et al.

In recent years, we have witnessed an increased interest in temporal modeling of patient records from large scale Electronic Health Records (EHR). While simpler RNN models have been used for such problems, memory networks, which in other domains were found to generalize well, are underutilized. Traditional memory networks involve diffused and non-linear operations where influence of past events on outputs are not readily quantifiable. We posit that this lack of interpretability makes such networks not applicable for EHR analysis. While networks with explicit memory have been proposed recently, the discontinuities imposed by the discrete operations make such networks harder to train and require more supervision. The problem is further exacerbated in the limited data setting of EHR studies. In this paper, we propose a novel memory architecture that is more interpretable than traditional memory networks while being easier to train than explicit memory banks. Inspired by well-known models of human cognition, we propose partitioning the external memory space into (a) a primary explicit memory block to store exact replicas of recent events to support interpretations, followed by (b) a secondary blurred memory block that accumulates salient aspects of past events dropped from the explicit block as higher level abstractions and allow training with less supervision by stabilize the gradients. We apply the model for 3 learning problems on ICU records from the MIMIC III database spanning millions of data points. Our model performs comparably to the state-of the art while also, crucially, enabling ready interpretation of the results.

Chengxi Zang, Fei Wang

Learning continuous-time dynamics on complex networks is crucial for understanding, predicting and controlling complex systems in science and engineering. However, this task is very challenging due to the combinatorial complexities in the structures of high dimensional systems, their elusive continuous-time nonlinear dynamics, and their structural-dynamic dependencies. To address these challenges, we propose to combine Ordinary Differential Equation Systems (ODEs) and Graph Neural Networks (GNNs) to learn continuous-time dynamics on complex networks in a data-driven manner. We model differential equation systems by GNNs. Instead of mapping through a discrete number of neural layers in the forward process, we integrate GNN layers over continuous time numerically, leading to capturing continuous-time dynamics on graphs. Our model can be interpreted as a Continuous-time GNN model or a Graph Neural ODEs model. Our model can be utilized for continuous-time network dynamics prediction, structured sequence prediction (a regularly-sampled case), and node semi-supervised classification tasks (a one-snapshot case) in a unified framework. We validate our model by extensive experiments in the above three scenarios. The promising experimental results demonstrate our model's capability of jointly capturing the structure and dynamics of complex systems in a unified framework.

Hongying Liu, Xiongjie Shen, Fanhua Shang et al.

This paper proposes a novel cascaded U-Net for brain tumor segmentation. Inspired by the distinct hierarchical structure of brain tumor, we design a cascaded deep network framework, in which the whole tumor is segmented firstly and then the tumor internal substructures are further segmented. Considering that the increase of the network depth brought by cascade structures leads to a loss of accurate localization information in deeper layers, we construct many skip connections to link features at the same resolution and transmit detailed information from shallow layers to the deeper layers. Then we present a loss weighted sampling (LWS) scheme to eliminate the issue of imbalanced data during training the network. Experimental results on BraTS 2017 data show that our architecture framework outperforms the state-of-the-art segmentation algorithms, especially in terms of segmentation sensitivity.

Xi Sheryl Zhang, Fengyi Tang, Hiroko Dodge et al.

In recent years, increasingly augmentation of health data, such as patient Electronic Health Records (EHR), are becoming readily available. This provides an unprecedented opportunity for knowledge discovery and data mining algorithms to dig insights from them, which can, later on, be helpful to the improvement of the quality of care delivery. Predictive modeling of clinical risk, including in-hospital mortality, hospital readmission, chronic disease onset, condition exacerbation, etc., from patient EHR, is one of the health data analytic problems that attract most of the interests. The reason is not only because the problem is important in clinical settings, but also there are challenges working with EHR such as sparsity, irregularity, temporality, etc. Different from applications in other domains such as computer vision and natural language processing, the labeled data samples in medicine (patients) are relatively limited, which creates lots of troubles for effective predictive model learning, especially for complicated models such as deep learning. In this paper, we propose MetaPred, a meta-learning for clinical risk prediction from longitudinal patient EHRs. In particular, in order to predict the target risk where there are limited data samples, we train a meta-learner from a set of related risk prediction tasks which learns how a good predictor is learned. The meta-learned can then be directly used in target risk prediction, and the limited available samples can be used for further fine-tuning the model performance. The effectiveness of MetaPred is tested on a real patient EHR repository from Oregon Health & Science University. We are able to demonstrate that with CNN and RNN as base predictors, MetaPred can achieve much better performance for predicting target risk with low resources comparing with the predictor trained on the limited samples available for this risk.

Ziyuan Pan, Hao Du, Kee Yuan Ngiam et al.

In critical care, intensivists are required to continuously monitor high dimensional vital signs and lab measurements to detect and diagnose acute patient conditions. This has always been a challenging task. In this study, we propose a novel self-correcting deep learning prediction approach to address this challenge. We focus on an example of the prediction of acute kidney injury (AKI). Compared with the existing models, our method has a number of distinct features: we utilized the accumulative data of patients in ICU; we developed a self-correcting mechanism that feeds errors from the previous predictions back into the network; we also proposed a regularization method that takes into account not only the model's prediction error on the label but also its estimation errors on the input data. This mechanism is applied in both regression and classification tasks. We compared the performance of our proposed method with the conventional deep learning models on two real-world clinical datasets and demonstrated that our proposed model constantly outperforms these baseline models. In particular, the proposed model achieved area under ROC curve at 0.893 on the MIMIC III dataset, and 0.871 on the Philips eICU dataset.

Guoqing Chao, Chengsheng Mao, Fei Wang et al.

ICU mortality risk prediction is a tough yet important task. On one hand, due to the complex temporal data collected, it is difficult to identify the effective features and interpret them easily; on the other hand, good prediction can help clinicians take timely actions to prevent the mortality. These correspond to the interpretability and accuracy problems. Most existing methods lack of the interpretability, but recently Subgraph Augmented Nonnegative Matrix Factorization (SANMF) has been successfully applied to time series data to provide a path to interpret the features well. Therefore, we adopted this approach as the backbone to analyze the patient data. One limitation of the raw SANMF method is its poor prediction ability due to its unsupervised nature. To deal with this problem, we proposed a supervised SANMF algorithm by integrating the logistic regression loss function into the NMF framework and solved it with an alternating optimization procedure. We used the simulation data to verify the effectiveness of this method, and then we applied it to ICU mortality risk prediction and demonstrated its superiority over other conventional supervised NMF methods.

Xi Sheryl Zhang, Jingyuan Chou, Fei Wang

With the arrival of the big data era, more and more data are becoming readily available in various real-world applications and those data are usually highly heterogeneous. Taking computational medicine as an example, we have both Electronic Health Records (EHR) and medical images for each patient. For complicated diseases such as Parkinson's and Alzheimer's, both EHR and neuroimaging information are very important for disease understanding because they contain complementary aspects of the disease. However, EHR and neuroimage are completely different. So far the existing research has been mainly focusing on one of them. In this paper, we proposed a framework, Memory-Based Graph Convolution Network (MemGCN), to perform integrative analysis with such multi-modal data. Specifically, GCN is used to extract useful information from the patients' neuroimages. The information contained in the patient EHRs before the acquisition of each brain image is captured by a memory network because of its sequential nature. The information contained in each brain image is combined with the information read out from the memory network to infer the disease state at the image acquisition timestamp. To further enhance the analytical power of MemGCN, we also designed a multi-hop strategy that allows multiple reading and updating on the memory can be performed at each iteration. We conduct experiments using the patient data from the Parkinson's Progression Markers Initiative (PPMI) with the task of classification of Parkinson's Disease (PD) cases versus controls. We demonstrate that superior classification performance can be achieved with our proposed framework, comparing with existing approaches involving a single type of data.

Xi Sheryl Zhang, Lifang He, Kun Chen et al.

Parkinson's Disease (PD) is one of the most prevalent neurodegenerative diseases that affects tens of millions of Americans. PD is highly progressive and heterogeneous. Quite a few studies have been conducted in recent years on predictive or disease progression modeling of PD using clinical and biomarkers data. Neuroimaging, as another important information source for neurodegenerative disease, has also arisen considerable interests from the PD community. In this paper, we propose a deep learning method based on Graph Convolutional Networks (GCN) for fusing multiple modalities of brain images in relationship prediction which is useful for distinguishing PD cases from controls. On Parkinson's Progression Markers Initiative (PPMI) cohort, our approach achieved $0.9537\pm 0.0587$ AUC, compared with $0.6443\pm 0.0223$ AUC achieved by traditional approaches such as PCA.

Yuan Luo, Chengsheng Mao, Yiben Yang et al.

Hypertension is a heterogeneous syndrome in need of improved subtyping using phenotypic and genetic measurements so that patients in different subtypes share similar pathophysiologic mechanisms and respond more uniformly to targeted treatments. Existing machine learning approaches often face challenges in integrating phenotype and genotype information and presenting to clinicians an interpretable model. We aim to provide informed patient stratification by introducing Hybrid Non-negative Matrix Factorization (HNMF) on phenotype and genotype matrices. HNMF simultaneously approximates the phenotypic and genetic matrices using different appropriate loss functions, and generates patient subtypes, phenotypic groups and genetic groups. Unlike previous methods, HNMF approximates phenotypic matrix under Frobenius loss, and genetic matrix under Kullback-Leibler (KL) loss. We propose an alternating projected gradient method to solve the approximation problem. Simulation shows HNMF converges fast and accurately to the true factor matrices. On real-world clinical dataset, we used the patient factor matrix as features to predict main cardiac mechanistic outcomes. We compared HNMF with six different models using phenotype or genotype features alone, with or without NMF, or using joint NMF with only one type of loss. HNMF significantly outperforms all comparison models. HNMF also reveals intuitive phenotype-genotype interactions that characterize cardiac abnormalities.

Mengying Sun, Fengyi Tang, Jinfeng Yi et al.

The surging availability of electronic medical records (EHR) leads to increased research interests in medical predictive modeling. Recently many deep learning based predicted models are also developed for EHR data and demonstrated impressive performance. However, a series of recent studies showed that these deep models are not safe: they suffer from certain vulnerabilities. In short, a well-trained deep network can be extremely sensitive to inputs with negligible changes. These inputs are referred to as adversarial examples. In the context of medical informatics, such attacks could alter the result of a high performance deep predictive model by slightly perturbing a patient's medical records. Such instability not only reflects the weakness of deep architectures, more importantly, it offers guide on detecting susceptible parts on the inputs. In this paper, we propose an efficient and effective framework that learns a time-preferential minimum attack targeting the LSTM model with EHR inputs, and we leverage this attack strategy to screen medical records of patients and identify susceptible events and measurements. The efficient screening procedure can assist decision makers to pay extra attentions to the locations that can cause severe consequence if not measured correctly. We conduct extensive empirical studies on a real-world urgent care cohort and demonstrate the effectiveness of the proposed screening approach.

Suyog Gupta, Wei Zhang, Fei Wang

This paper presents Rudra, a parameter server based distributed computing framework tuned for training large-scale deep neural networks. Using variants of the asynchronous stochastic gradient descent algorithm we study the impact of synchronization protocol, stale gradient updates, minibatch size, learning rates, and number of learners on runtime performance and model accuracy. We introduce a new learning rate modulation strategy to counter the effect of stale gradients and propose a new synchronization protocol that can effectively bound the staleness in gradients, improve runtime performance and achieve good model accuracy. Our empirical investigation reveals a principled approach for distributed training of neural networks: the mini-batch size per learner should be reduced as more learners are added to the system to preserve the model accuracy. We validate this approach using commonly-used image classification benchmarks: CIFAR10 and ImageNet.