Ping Zhang

Thai-Hoang Pham, Xueru Zhang, Ping Zhang

As machine learning (ML) algorithms are increasingly used in high-stakes applications, concerns have arisen that they may be biased against certain social groups. Although many approaches have been proposed to make ML models fair, they typically rely on the assumption that data distributions in training and deployment are identical. Unfortunately, this is commonly violated in practice and a model that is fair during training may lead to an unexpected outcome during its deployment. Although the problem of designing robust ML models under dataset shifts has been widely studied, most existing works focus only on the transfer of accuracy. In this paper, we study the transfer of both fairness and accuracy under domain generalization where the data at test time may be sampled from never-before-seen domains. We first develop theoretical bounds on the unfairness and expected loss at deployment, and then derive sufficient conditions under which fairness and accuracy can be perfectly transferred via invariant representation learning. Guided by this, we design a learning algorithm such that fair ML models learned with training data still have high fairness and accuracy when deployment environments change. Experiments on real-world data validate the proposed algorithm. Model implementation is available at https://github.com/pth1993/FATDM.

Changchang Yin, Pin-Yu Chen, Bingsheng Yao et al.

Sepsis is the leading cause of in-hospital mortality in the USA. Early sepsis onset prediction and diagnosis could significantly improve the survival of sepsis patients. Existing predictive models are usually trained on high-quality data with few missing information, while missing values widely exist in real-world clinical scenarios (especially in the first hours of admissions to the hospital), which causes a significant decrease in accuracy and an increase in uncertainty for the predictive models. The common method to handle missing values is imputation, which replaces the unavailable variables with estimates from the observed data. The uncertainty of imputation results can be propagated to the sepsis prediction outputs, which have not been studied in existing works on either sepsis prediction or uncertainty quantification. In this study, we first define such propagated uncertainty as the variance of prediction output and then introduce uncertainty propagation methods to quantify the propagated uncertainty. Moreover, for the potential high-risk patients with low confidence due to limited observations, we propose a robust active sensing algorithm to increase confidence by actively recommending clinicians to observe the most informative variables. We validate the proposed models in both publicly available data (i.e., MIMIC-III and AmsterdamUMCdb) and proprietary data in The Ohio State University Wexner Medical Center (OSUWMC). The experimental results show that the propagated uncertainty is dominant at the beginning of admissions to hospitals and the proposed algorithm outperforms state-of-the-art active sensing methods. Finally, we implement a SepsisLab system for early sepsis prediction and active sensing based on our pre-trained models. Clinicians and potential sepsis patients can benefit from the system in early prediction and diagnosis of sepsis.

Jianxun Ren, Ning An, Youjia Zhang et al.

Cortical surface registration plays a crucial role in aligning cortical functional and anatomical features across individuals. However, conventional registration algorithms are computationally inefficient. Recently, learning-based registration algorithms have emerged as a promising solution, significantly improving processing efficiency. Nonetheless, there remains a gap in the development of a learning-based method that exceeds the state-of-the-art conventional methods simultaneously in computational efficiency, registration accuracy, and distortion control, despite the theoretically greater representational capabilities of deep learning approaches. To address the challenge, we present SUGAR, a unified unsupervised deep-learning framework for both rigid and non-rigid registration. SUGAR incorporates a U-Net-based spherical graph attention network and leverages the Euler angle representation for deformation. In addition to the similarity loss, we introduce fold and multiple distortion losses, to preserve topology and minimize various types of distortions. Furthermore, we propose a data augmentation strategy specifically tailored for spherical surface registration, enhancing the registration performance. Through extensive evaluation involving over 10,000 scans from 7 diverse datasets, we showed that our framework exhibits comparable or superior registration performance in accuracy, distortion, and test-retest reliability compared to conventional and learning-based methods. Additionally, SUGAR achieves remarkable sub-second processing times, offering a notable speed-up of approximately 12,000 times in registering 9,000 subjects from the UK Biobank dataset in just 32 minutes. This combination of high registration performance and accelerated processing time may greatly benefit large-scale neuroimaging studies.

Changchang Yin, Ruoqi Liu, Jeffrey Caterino et al.

Despite intense efforts in basic and clinical research, an individualized ventilation strategy for critically ill patients remains a major challenge. Recently, dynamic treatment regime (DTR) with reinforcement learning (RL) on electronic health records (EHR) has attracted interest from both the healthcare industry and machine learning research community. However, most learned DTR policies might be biased due to the existence of confounders. Although some treatment actions non-survivors received may be helpful, if confounders cause the mortality, the training of RL models guided by long-term outcomes (e.g., 90-day mortality) would punish those treatment actions causing the learned DTR policies to be suboptimal. In this study, we develop a new deconfounding actor-critic network (DAC) to learn optimal DTR policies for patients. To alleviate confounding issues, we incorporate a patient resampling module and a confounding balance module into our actor-critic framework. To avoid punishing the effective treatment actions non-survivors received, we design a short-term reward to capture patients' immediate health state changes. Combining short-term with long-term rewards could further improve the model performance. Moreover, we introduce a policy adaptation method to successfully transfer the learned model to new-source small-scale datasets. The experimental results on one semi-synthetic and two different real-world datasets show the proposed model outperforms the state-of-the-art models. The proposed model provides individualized treatment decisions for mechanical ventilation that could improve patient outcomes.

Zishan Gu, Changchang Yin, Fenglin Liu et al.

Large Vision Language Models (LVLMs) have recently achieved superior performance in various tasks on natural image and text data, which inspires a large amount of studies for LVLMs fine-tuning and training. Despite their advancements, there has been scant research on the robustness of these models against hallucination when fine-tuned on smaller datasets. In this study, we introduce a new benchmark dataset, the Medical Visual Hallucination Test (MedVH), to evaluate the hallucination of domain-specific LVLMs. MedVH comprises five tasks to evaluate hallucinations in LVLMs within the medical context, which includes tasks for comprehensive understanding of textual and visual input, as well as long textual response generation. Our extensive experiments with both general and medical LVLMs reveal that, although medical LVLMs demonstrate promising performance on standard medical tasks, they are particularly susceptible to hallucinations, often more so than the general models, raising significant concerns about the reliability of these domain-specific models. For medical LVLMs to be truly valuable in real-world applications, they must not only accurately integrate medical knowledge but also maintain robust reasoning abilities to prevent hallucination. Our work paves the way for future evaluations of these studies.

Ruhan Liu, Jiajia Li, Yang Wen et al.

Objective: COVID-19 has spread worldwide and made a huge influence across the world. Modeling the infectious spread situation of COVID-19 is essential to understand the current condition and to formulate intervention measurements. Epidemiological equations based on the SEIR model simulate disease development. The traditional parameter estimation method to solve SEIR equations could not precisely fit real-world data due to different situations, such as social distancing policies and intervention strategies. Additionally, learning-based models achieve outstanding fitting performance, but cannot visualize mechanisms. Methods: Thus, we propose a deep dynamic epidemiological (DDE) method that combines epidemiological equations and deep-learning advantages to obtain high accuracy and visualization. The DDE contains deep networks to fit the effect function to simulate the ever-changing situations based on the neural ODE method in solving variants' equations, ensuring the fitting performance of multi-level areas. Results: We introduce four SEIR variants to fit different situations in different countries and regions. We compare our DDE method with traditional parameter estimation methods (Nelder-Mead, BFGS, Powell, Truncated Newton Conjugate-Gradient, Neural ODE) in fitting the real-world data in the cases of countries (the USA, Columbia, South Africa) and regions (Wuhan in China, Piedmont in Italy). Our DDE method achieves the best Mean Square Error and Pearson coefficient in all five areas. Further, compared with the state-of-art learning-based approaches, the DDE outperforms all techniques, including LSTM, RNN, GRU, Random Forest, Extremely Random Trees, and Decision Tree. Conclusion: DDE presents outstanding predictive ability and visualized display of the changes in infection rates in different regions and countries.

Biplob Biswas, Thai-Hoang Pham, Ping Zhang

International Classification of Disease (ICD) coding procedure which refers to tagging medical notes with diagnosis codes has been shown to be effective and crucial to the billing system in medical sector. Currently, ICD codes are assigned to a clinical note manually which is likely to cause many errors. Moreover, training skilled coders also requires time and human resources. Therefore, automating the ICD code determination process is an important task. With the advancement of artificial intelligence theory and computational hardware, machine learning approach has emerged as a suitable solution to automate this process. In this project, we apply a transformer-based architecture to capture the interdependence among the tokens of a document and then use a code-wise attention mechanism to learn code-specific representations of the entire document. Finally, they are fed to separate dense layers for corresponding code prediction. Furthermore, to handle the imbalance in the code frequency of clinical datasets, we employ a label distribution aware margin (LDAM) loss function. The experimental results on the MIMIC-III dataset show that our proposed model outperforms other baselines by a significant margin. In particular, our best setting achieves a micro-AUC score of 0.923 compared to 0.868 of bidirectional recurrent neural networks. We also show that by using the code-wise attention mechanism, the model can provide more insights about its prediction, and thus it can support clinicians to make reliable decisions. Our code is available online (https://github.com/biplob1ly/TransICD)

Ruoqi Liu, Lingfei Wu, Ping Zhang

Treatment effect estimation (TEE) is the task of determining the impact of various treatments on patient outcomes. Current TEE methods fall short due to reliance on limited labeled data and challenges posed by sparse and high-dimensional observational patient data. To address the challenges, we introduce a novel pre-training and fine-tuning framework, KG-TREAT, which synergizes large-scale observational patient data with biomedical knowledge graphs (KGs) to enhance TEE. Unlike previous approaches, KG-TREAT constructs dual-focus KGs and integrates a deep bi-level attention synergy method for in-depth information fusion, enabling distinct encoding of treatment-covariate and outcome-covariate relationships. KG-TREAT also incorporates two pre-training tasks to ensure a thorough grounding and contextualization of patient data and KGs. Evaluation on four downstream TEE tasks shows KG-TREAT's superiority over existing methods, with an average improvement of 7% in Area under the ROC Curve (AUC) and 9% in Influence Function-based Precision of Estimating Heterogeneous Effects (IF-PEHE). The effectiveness of our estimated treatment effects is further affirmed by alignment with established randomized clinical trial findings.

Changchang Yin, Shihan Fu, Bingsheng Yao et al.

Sepsis is an organ dysfunction caused by a deregulated immune response to an infection. Early sepsis prediction and identification allow for timely intervention, leading to improved clinical outcomes. Clinical calculators (e.g., the six-organ dysfunction assessment of SOFA) play a vital role in sepsis identification within clinicians' workflow, providing evidence-based risk assessments essential for sepsis diagnosis. However, artificial intelligence (AI) sepsis prediction models typically generate a single sepsis risk score without incorporating clinical calculators for assessing organ dysfunctions, making the models less convincing and transparent to clinicians. To bridge the gap, we propose to mimic clinicians' workflow with a novel framework SepsisCalc to integrate clinical calculators into the predictive model, yielding a clinically transparent and precise model for utilization in clinical settings. Practically, clinical calculators usually combine information from multiple component variables in Electronic Health Records (EHR), and might not be applicable when the variables are (partially) missing. We mitigate this issue by representing EHRs as temporal graphs and integrating a learning module to dynamically add the accurately estimated calculator to the graphs. Experimental results on real-world datasets show that the proposed model outperforms state-of-the-art methods on sepsis prediction tasks. Moreover, we developed a system to identify organ dysfunctions and potential sepsis risks, providing a human-AI interaction tool for deployment, which can help clinicians understand the prediction outputs and prepare timely interventions for the corresponding dysfunctions, paving the way for actionable clinical decision-making support for early intervention.

Ping Zhang, Zheda Mai, Quang-Huy Nguyen et al.

Semi-supervised learning (SSL) leverages abundant unlabeled data alongside limited labeled data to enhance learning. As vision foundation models (VFMs) increasingly serve as the backbone of vision applications, it remains unclear how SSL interacts with these pre-trained models. To address this gap, we develop new SSL benchmark datasets where frozen VFMs underperform and systematically evaluate representative SSL methods. We make a surprising observation: parameter-efficient fine-tuning (PEFT) using only labeled data often matches SSL performance, even without leveraging unlabeled data. This motivates us to revisit self-training, a conceptually simple SSL baseline, where we use the supervised PEFT model to pseudo-label unlabeled data for further training. To overcome the notorious issue of noisy pseudo-labels, we propose ensembling multiple PEFT approaches and VFM backbones to produce more robust pseudo-labels. Empirical results validate the effectiveness of this simple yet powerful approach, providing actionable insights into SSL with VFMs and paving the way for more scalable and practical semi-supervised learning in the era of foundation models.

Seungyeon Lee, Ruoqi Liu, Feixiong Cheng et al.

Drug repurposing identifies new therapeutic uses for existing drugs, reducing the time and costs compared to traditional de novo drug discovery. Most existing drug repurposing studies using real-world patient data often treat the entire population as homogeneous, ignoring the heterogeneity of treatment responses across patient subgroups. This approach may overlook promising drugs that benefit specific subgroups but lack notable treatment effects across the entire population, potentially limiting the number of repurposable candidates identified. To address this, we introduce STEDR, a novel drug repurposing framework that integrates subgroup analysis with treatment effect estimation. Our approach first identifies repurposing candidates by emulating multiple clinical trials on real-world patient data and then characterizes patient subgroups by learning subgroup-specific treatment effects. We deploy \model to Alzheimer's Disease (AD), a condition with few approved drugs and known heterogeneity in treatment responses. We emulate trials for over one thousand medications on a large-scale real-world database covering over 8 million patients, identifying 14 drug candidates with beneficial effects to AD in characterized subgroups. Experiments demonstrate STEDR's superior capability in identifying repurposing candidates compared to existing approaches. Additionally, our method can characterize clinically relevant patient subgroups associated with important AD-related risk factors, paving the way for precision drug repurposing.

Yuanlong Wang, Pengqi Wang, Changchang Yin et al.

Living environments play a vital role in the prevalence and progression of diseases, and understanding their impact on patient's health status becomes increasingly crucial for developing AI models. However, due to the lack of long-term and fine-grained spatial and temporal data in public and population health studies, most existing studies fail to incorporate environmental data, limiting the models' performance and real-world application. To address this shortage, we developed SatHealth, a novel dataset combining multimodal spatiotemporal data, including environmental data, satellite images, all-disease prevalences estimated from medical claims, and social determinants of health (SDoH) indicators. We conducted experiments under two use cases with SatHealth: regional public health modeling and personal disease risk prediction. Experimental results show that living environmental information can significantly improve AI models' performance and temporal-spatial generalizability on various tasks. Finally, we deploy a web-based application to provide an exploration tool for SatHealth and one-click access to both our data and regional environmental embedding to facilitate plug-and-play utilization. SatHealth is now published with data in Ohio, and we will keep updating SatHealth to cover the other parts of the US. With the web application and published code pipeline, our work provides valuable angles and resources to include environmental data in healthcare research and establishes a foundational framework for future research in environmental health informatics.

Zicong Zhang, Changchang Yin, Ping Zhang

Disease progression modeling (DPM) involves using mathematical frameworks to quantitatively measure the severity of how certain disease progresses. DPM is useful in many ways such as predicting health state, categorizing disease stages, and assessing patients disease trajectory etc. Recently, with wider availability of electronic health records (EHR) and the broad application of data-driven machine learning method, DPM has attracted much attention yet remains two major challenges: (i) Due to the existence of irregularity, heterogeneity and long-term dependency in EHRs, most existing DPM methods might not be able to provide comprehensive patient representations. (ii) Lots of records in EHRs might be irrelevant to the target disease. Most existing models learn to automatically focus on the relevant information instead of explicitly capture the target-relevant events, which might make the learned model suboptimal. To address these two issues, we propose Temporal Clustering with External Memory Network (TC-EMNet) for DPM that groups patients with similar trajectories to form disease clusters/stages. TC-EMNet uses a variational autoencoder (VAE) to capture internal complexity from the input data and utilizes an external memory work to capture long term distance information, both of which are helpful for producing comprehensive patient states. Last but not least, k-means algorithm is adopted to cluster the extracted comprehensive patient states to capture disease progression. Experiments on two real-world datasets show that our model demonstrates competitive clustering performance against state-of-the-art methods and is able to identify clinically meaningful clusters. The visualization of the extracted patient states shows that the proposed model can generate better patient states than the baselines.

Ruoqi Liu, Changchang Yin, Ping Zhang

Estimating the individual treatment effect (ITE) from observational data is meaningful and practical in healthcare. Existing work mainly relies on the strong ignorability assumption that no hidden confounders exist, which may lead to bias in estimating causal effects. Some studies consider the hidden confounders are designed for static environment and not easily adaptable to a dynamic setting. In fact, most observational data (e.g., electronic medical records) is naturally dynamic and consists of sequential information. In this paper, we propose Deep Sequential Weighting (DSW) for estimating ITE with time-varying confounders. Specifically, DSW infers the hidden confounders by incorporating the current treatment assignments and historical information using a deep recurrent weighting neural network. The learned representations of hidden confounders combined with current observed data are leveraged for potential outcome and treatment predictions. We compute the time-varying inverse probabilities of treatment for re-weighting the population. We conduct comprehensive comparison experiments on fully-synthetic, semi-synthetic and real-world datasets to evaluate the performance of our model and baselines. Results demonstrate that our model can generate unbiased and accurate treatment effect by conditioning both time-varying observed and hidden confounders, paving the way for personalized medicine.

Ruoqi Liu, Lai Wei, Ping Zhang

Drug repurposing is an effective strategy to identify new uses for existing drugs, providing the quickest possible transition from bench to bedside. Existing methods for drug repurposing that mainly focus on pre-clinical information may exist translational issues when applied to human beings. Real world data (RWD), such as electronic health records and insurance claims, provide information on large cohorts of users for many drugs. Here we present an efficient and easily-customized framework for generating and testing multiple candidates for drug repurposing using a retrospective analysis of RWDs. Building upon well-established causal inference and deep learning methods, our framework emulates randomized clinical trials for drugs present in a large-scale medical claims database. We demonstrate our framework in a case study of coronary artery disease (CAD) by evaluating the effect of 55 repurposing drug candidates on various disease outcomes. We achieve 6 drug candidates that significantly improve the CAD outcomes but not have been indicated for treating CAD, paving the way for drug repurposing.

Bernal Jiménez Gutiérrez, Juncheng Zeng, Dongdong Zhang et al.

The global pandemic has made it more important than ever to quickly and accurately retrieve relevant scientific literature for effective consumption by researchers in a wide range of fields. We provide an analysis of several multi-label document classification models on the LitCovid dataset, a growing collection of 23,000 research papers regarding the novel 2019 coronavirus. We find that pre-trained language models fine-tuned on this dataset outperform all other baselines and that BioBERT surpasses the others by a small margin with micro-F1 and accuracy scores of around 86% and 75% respectively on the test set. We evaluate the data efficiency and generalizability of these models as essential features of any system prepared to deal with an urgent situation like the current health crisis. Finally, we explore 50 errors made by the best performing models on LitCovid documents and find that they often (1) correlate certain labels too closely together and (2) fail to focus on discriminative sections of the articles; both of which are important issues to address in future work. Both data and code are available on GitHub.

Xiang Yue, Zhen Wang, Jingong Huang et al.

Graph embedding learning that aims to automatically learn low-dimensional node representations, has drawn increasing attention in recent years. To date, most recent graph embedding methods are evaluated on social and information networks and are not comprehensively studied on biomedical networks under systematic experiments and analyses. On the other hand, for a variety of biomedical network analysis tasks, traditional techniques such as matrix factorization (which can be seen as a type of graph embedding methods) have shown promising results, and hence there is a need to systematically evaluate the more recent graph embedding methods (e.g. random walk-based and neural network-based) in terms of their usability and potential to further the state-of-the-art. We select 11 representative graph embedding methods and conduct a systematic comparison on 3 important biomedical link prediction tasks: drug-disease association (DDA) prediction, drug-drug interaction (DDI) prediction, protein-protein interaction (PPI) prediction; and 2 node classification tasks: medical term semantic type classification, protein function prediction. Our experimental results demonstrate that the recent graph embedding methods achieve promising results and deserve more attention in the future biomedical graph analysis. Compared with three state-of-the-art methods for DDAs, DDIs and protein function predictions, the recent graph embedding methods achieve competitive performance without using any biological features and the learned embeddings can be treated as complementary representations for the biological features. By summarizing the experimental results, we provide general guidelines for properly selecting graph embedding methods and setting their hyper-parameters for different biomedical tasks.