Fusheng Wang

Fusheng Wang, Yikai Hou

This paper proposes Spectra-Guided Neural Tucker Factorization (SG-NTF) for High-Dimensional and Incomplete (HDI) tensor completion. Circumventing discrete representational limits, SG-NTF maps scalar timestamps into a continuous spectral space to abstract temporal periodicities. Concurrently, a Spatio-Temporal Co-Gating (STCG) mechanism explicitly filters latent interactions via multiplicative modulation on spatiotemporal contexts. Evaluations on real-world HDI tensors verify that SG-NTF maintains competitive completion accuracy with parameter efficiency.

Weimin Lyu, Xinyu Dong, Rachel Wong et al.

Deep-learning-based clinical decision support using structured electronic health records (EHR) has been an active research area for predicting risks of mortality and diseases. Meanwhile, large amounts of narrative clinical notes provide complementary information, but are often not integrated into predictive models. In this paper, we provide a novel multimodal transformer to fuse clinical notes and structured EHR data for better prediction of in-hospital mortality. To improve interpretability, we propose an integrated gradients (IG) method to select important words in clinical notes and discover the critical structured EHR features with Shapley values. These important words and clinical features are visualized to assist with interpretation of the prediction outcomes. We also investigate the significance of domain adaptive pretraining and task adaptive fine-tuning on the Clinical BERT, which is used to learn the representations of clinical notes. Experiments demonstrated that our model outperforms other methods (AUCPR: 0.538, AUCROC: 0.877, F1:0.490).

Jianyuan Deng, Zhibo Yang, Hehe Wang et al.

Artificial intelligence (AI) has been widely applied in drug discovery with a major task as molecular property prediction. Despite booming techniques in molecular representation learning, key elements underlying molecular property prediction remain largely unexplored, which impedes further advancements in this field. Herein, we conduct an extensive evaluation of representative models using various representations on the MoleculeNet datasets, a suite of opioids-related datasets and two additional activity datasets from the literature. To investigate the predictive power in low-data and high-data space, a series of descriptors datasets of varying sizes are also assembled to evaluate the models. In total, we have trained 62,820 models, including 50,220 models on fixed representations, 4,200 models on SMILES sequences and 8,400 models on molecular graphs. Based on extensive experimentation and rigorous comparison, we show that representation learning models exhibit limited performance in molecular property prediction in most datasets. Besides, multiple key elements underlying molecular property prediction can affect the evaluation results. Furthermore, we show that activity cliffs can significantly impact model prediction. Finally, we explore into potential causes why representation learning models can fail and show that dataset size is essential for representation learning models to excel.

Lyuheng Yuan, Da Yan, Akhlaque Ahmad et al.

Spatial join is a fundamental operation in spatial databases. With the rapid growth of 3D data in applications such as LiDAR-based object detection and 3D digital pathology, there is an increasing need to support spatial join over 3D datasets. However, existing techniques are largely designed for 2D data, leaving 3D spatial join underexplored and computationally expensive. We present 3DPipe, a pipelined GPU framework for scalable spatial join over polyhedral objects. 3DPipe exploits GPU parallelism across both filtering and refinement stages, incorporates a multi-level pruning strategy for efficient candidate reduction, and employs chunked streaming to handle datasets exceeding GPU memory. Its pipelined execution overlaps CPU data preparation, host-device data transfer, and GPU computation to improve throughput. Experiments show that 3DPipe achieves up to 9.0$\times$ speedup over the state-of-the-art GPU solution, TDBase, while maintaining excellent scalability. 3DPipe is open-sourced at https://github.com/lyuheng/3dpipe.

Weimin Lyu, Zexin Bi, Fusheng Wang et al.

The advent of clinical language models integrated into electronic health records (EHR) for clinical decision support has marked a significant advancement, leveraging the depth of clinical notes for improved decision-making. Despite their success, the potential vulnerabilities of these models remain largely unexplored. This paper delves into the realm of backdoor attacks on clinical language models, introducing an innovative attention-based backdoor attack method, BadCLM (Bad Clinical Language Models). This technique clandestinely embeds a backdoor within the models, causing them to produce incorrect predictions when a pre-defined trigger is present in inputs, while functioning accurately otherwise. We demonstrate the efficacy of BadCLM through an in-hospital mortality prediction task with MIMIC III dataset, showcasing its potential to compromise model integrity. Our findings illuminate a significant security risk in clinical decision support systems and pave the way for future endeavors in fortifying clinical language models against such vulnerabilities.

Jianyuan Deng, Zhibo Yang, Iwao Ojima et al.

Artificial intelligence (AI) has been transforming the practice of drug discovery in the past decade. Various AI techniques have been used in a wide range of applications, such as virtual screening and drug design. In this survey, we first give an overview on drug discovery and discuss related applications, which can be reduced to two major tasks, i.e., molecular property prediction and molecule generation. We then discuss common data resources, molecule representations and benchmark platforms. Furthermore, to summarize the progress of AI in drug discovery, we present the relevant AI techniques including model architectures and learning paradigms in the papers surveyed. We expect that this survey will serve as a guide for researchers who are interested in working at the interface of artificial intelligence and drug discovery. We also provide a GitHub repository (https://github.com/dengjianyuan/Survey_AI_Drug_Discovery) with the collection of papers and codes, if applicable, as a learning resource, which is regularly updated.

Zhan Shi, Jingwei Zhang, Jun Kong et al.

In digital pathology, the multiple instance learning (MIL) strategy is widely used in the weakly supervised histopathology whole slide image (WSI) classification task where giga-pixel WSIs are only labeled at the slide level. However, existing attention-based MIL approaches often overlook contextual information and intrinsic spatial relationships between neighboring tissue tiles, while graph-based MIL frameworks have limited power to recognize the long-range dependencies. In this paper, we introduce the integrative graph-transformer framework that simultaneously captures the context-aware relational features and global WSI representations through a novel Graph Transformer Integration (GTI) block. Specifically, each GTI block consists of a Graph Convolutional Network (GCN) layer modeling neighboring relations at the local instance level and an efficient global attention model capturing comprehensive global information from extensive feature embeddings. Extensive experiments on three publicly available WSI datasets: TCGA-NSCLC, TCGA-RCC and BRIGHT, demonstrate the superiority of our approach over current state-of-the-art MIL methods, achieving an improvement of 1.0% to 2.6% in accuracy and 0.7%-1.6% in AUROC.

Yinan Liu, Xinyu Dong, Weimin Lyu et al.

Class imbalance problems widely exist in the medical field and heavily deteriorates performance of clinical predictive models. Most techniques to alleviate the problem rebalance class proportions and they predominantly assume the rebalanced proportions should be a function of the original data and oblivious to the model one uses. This work challenges this prevailing assumption and proposes that links the optimal class proportions to the model complexity, thereby tuning the class proportions per model. Our experiments on the opioid overdose prediction problem highlight the performance gain of tuning class proportions. Rigorous regression analysis also confirms the advantages of the theoretical framework proposed and the statistically significant correlation between the hyperparameters controlling the model complexity and the optimal class proportions.

Fusheng Wang, Jianhao Yan, Fandong Meng et al.

Neural Machine Translation (NMT) models achieve state-of-the-art performance on many translation benchmarks. As an active research field in NMT, knowledge distillation is widely applied to enhance the model's performance by transferring teacher model's knowledge on each training sample. However, previous work rarely discusses the different impacts and connections among these samples, which serve as the medium for transferring teacher knowledge. In this paper, we design a novel protocol that can effectively analyze the different impacts of samples by comparing various samples' partitions. Based on above protocol, we conduct extensive experiments and find that the teacher's knowledge is not the more, the better. Knowledge over specific samples may even hurt the whole performance of knowledge distillation. Finally, to address these issues, we propose two simple yet effective strategies, i.e., batch-level and global-level selections, to pick suitable samples for distillation. We evaluate our approaches on two large-scale machine translation tasks, WMT'14 English->German and WMT'19 Chinese->English. Experimental results show that our approaches yield up to +1.28 and +0.89 BLEU points improvements over the Transformer baseline, respectively.

Yu Wang, Ziqiao Guan, Wei Hou et al.

Chronic kidney disease (CKD) has a poor prognosis due to excessive risk factors and comorbidities associated with it. The early detection of CKD faces challenges of insufficient medical histories of positive patients and complicated risk factors. In this paper, we propose the TRACE (Transformer-RNN Autoencoder-enhanced CKD Detector) framework, an end-to-end prediction model using patients' medical history data, to deal with these challenges. TRACE presents a comprehensive medical history representation with a novel key component: a Transformer-RNN autoencoder. The autoencoder jointly learns a medical concept embedding via Transformer for each hospital visit, and a latent representation which summarizes a patient's medical history across all the visits. We compared TRACE with multiple state-of-the-art methods on a dataset derived from real-world medical records. Our model has achieved 0.5708 AUPRC with a 2.31% relative improvement over the best-performing method. We also validated the clinical meaning of the learned embeddings through visualizations and a case study, showing the potential of TRACE to serve as a general disease prediction model.

Xinyu Dong, Jianyuan Deng, Sina Rashidian et al.

The United States is experiencing an opioid epidemic, and there were more than 10 million opioid misusers aged 12 or older each year. Identifying patients at high risk of Opioid Use Disorder (OUD) can help to make early clinical interventions to reduce the risk of OUD. Our goal is to predict OUD patients among opioid prescription users through analyzing electronic health records with machine learning and deep learning methods. This will help us to better understand the diagnoses of OUD, providing new insights on opioid epidemic. Electronic health records of patients who have been prescribed with medications containing active opioid ingredients were extracted from Cerner Health Facts database between January 1, 2008 and December 31, 2017. Long Short-Term Memory (LSTM) models were applied to predict opioid use disorder risk in the future based on recent five encounters, and compared to Logistic Regression, Random Forest, Decision Tree and Dense Neural Network. Prediction performance was assessed using F-1 score, precision, recall, and AUROC. Our temporal deep learning model provided promising prediction results which outperformed other methods, with a F1 score of 0.8023 and AUCROC of 0.9369. The model can identify OUD related medications and vital signs as important features for the prediction. LSTM based temporal deep learning model is effective on predicting opioid use disorder using a patient past history of electronic health records, with minimal domain knowledge. It has potential to improve clinical decision support for early intervention and prevention to combat the opioid epidemic.

Jianyuan Deng, Zhibo Yang, Yao Li et al.

Naloxone, an opioid antagonist, has been widely used to save lives from opioid overdose, a leading cause for death in the opioid epidemic. However, naloxone has short brain retention ability, which limits its therapeutic efficacy. Developing better opioid antagonists is critical in combating the opioid epidemic.Instead of exhaustively searching in a huge chemical space for better opioid antagonists, we adopt reinforcement learning which allows efficient gradient-based search towards molecules with desired physicochemical and/or biological properties. Specifically, we implement a deep reinforcement learning framework to discover potential lead compounds as better opioid antagonists with enhanced brain retention ability. A customized multi-objective reward function is designed to bias the generation towards molecules with both sufficient opioid antagonistic effect and enhanced brain retention ability. Thorough evaluation demonstrates that with this framework, we are able to identify valid, novel and feasible molecules with multiple desired properties, which has high potential in drug discovery.

Xiaoyuan Guo, Fusheng Wang, George Teodorou et al.

Liver steatosis is known as the abnormal accumulation of lipids within cells. An accurate quantification of steatosis area within the liver histopathological microscopy images plays an important role in liver disease diagnosis and trans-plantation assessment. Such a quantification analysis often requires a precise steatosis segmentation that is challenging due to abundant presence of highly overlapped steatosis droplets. In this paper, a deep learning model Mask-RCNN is used to segment the steatosis droplets in clumps. Extended from Faster R-CNN, Mask-RCNN can predict object masks in addition to bounding box detection. With transfer learning, the resulting model is able to segment overlapped steatosis regions at 75.87% by Average Precision, 60.66% by Recall,65.88% by F1-score, and 76.97% by Jaccard index, promising to support liver disease diagnosis and allograft rejection prediction in future clinical practice.

Sina Rashidian, Janos Hajagos, Richard Moffitt et al.

Characterization of a patient clinical phenotype is central to biomedical informatics. ICD codes, assigned to inpatient encounters by coders, is important for population health and cohort discovery when clinical information is limited. While ICD codes are assigned to patients by professionals trained and certified in coding there is substantial variability in coding. We present a methodology that uses deep learning methods to model coder decision making and that predicts ICD codes. Our approach predicts codes based on demographics, lab results, and medications, as well as codes from previous encounters. We are able to predict existing codes with high accuracy for all three of the test cases we investigated: diabetes, acute renal failure, and chronic kidney disease. We employed a panel of clinicians, in a blinded manner, to assess ground truth and compared the predictions of coders, model and clinicians. When disparities between the model prediction and coder assigned codes were reviewed, our model outperformed coder assigned ICD codes.

Mousumi Roy, Fusheng Wang, George Teodoro et al.

Cellular phenotypic features derived from histopathology images are the basis of pathologic diagnosis and are thought to be related to underlying molecular profiles. Due to overwhelming cell numbers and population heterogeneity, it remains challenging to quantitatively compute and compare features of cells with distinct molecular signatures. In this study, we propose a self-reliant and efficient analysis framework that supports quantitative analysis of cellular phenotypic difference across distinct molecular groups. To demonstrate efficacy, we quantitatively analyze astrocytomas that are molecularly characterized as either Isocitrate Dehydrogenase (IDH) mutant (MUT) or wildtype (WT) using imaging data from The Cancer Genome Atlas database. Representative cell instances that are phenotypically different between these two groups are retrieved after segmentation, feature computation, data pruning, dimensionality reduction, and unsupervised clustering. Our analysis is generic and can be applied to a wide set of cell-based biomedical research.

Mousumi Roy, Fusheng Wang, George Teodoro et al.

An accurate steatosis quantification with pathology tissue samples is of high clinical importance. However, such pathology measurement is manually made in most clinical practices, subject to severe reader variability due to large sampling bias and poor reproducibility. Although some computerized automated methods are developed to quantify the steatosis regions, they present limited analysis capacity for high resolution whole-slide microscopy images and accurate overlapped steatosis division. In this paper, we propose a method that extracts an individual whole tissue piece at high resolution with minimum background area by estimating tissue bounding box and rotation angle. This is followed by the segmentation and segregation of steatosis regions with high curvature point detection and an ellipse fitting quality assessment method. We validate our method with isolated and overlapped steatosis regions in liver tissue images of 11 patients. The experimental results suggest that our method is promising for enhanced support of steatosis quantization during the pathology review for liver disease treatment.

Alevtina Dubovitskaya, Zhigang Xu, Samuel Ryu et al.

Electronic medical records (EMRs) are critical, highly sensitive private information in healthcare, and need to be frequently shared among peers. Blockchain provides a shared, immutable and transparent history of all the transactions to build applications with trust, accountability and transparency. This provides a unique opportunity to develop a secure and trustable EMR data management and sharing system using blockchain. In this paper, we present our perspectives on blockchain based healthcare data management, in particular, for EMR data sharing between healthcare providers and for research studies. We propose a framework on managing and sharing EMR data for cancer patient care. In collaboration with Stony Brook University Hospital, we implemented our framework in a prototype that ensures privacy, security, availability, and fine-grained access control over EMR data. The proposed work can significantly reduce the turnaround time for EMR sharing, improve decision making for medical care, and reduce the overall cost