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Yuan Luo

Publications and source records attributed to Yuan Luo.

At least 73 records · Page 4Linked to original sources

IRTCI: Item Response Theory for Categorical Imputation

Most datasets suffer from partial or complete missing values, which has downstream limitations on the available models on which to test the data and on any statistical inferences that can be made from the data. Several imputation techniques have been designed to replace missing data with stand in values. The various approaches have implications for calculating clinical scores, model building and model testing. The work showcased here offers a novel means for categorical imputation based on item response theory (IRT) and compares it against several methodologies currently used in the machine learning field including k-nearest neighbors (kNN), multiple imputed chained equations (MICE) and Amazon Web Services (AWS) deep learning method, Datawig. Analyses comparing these techniques were performed on three different datasets that represented ordinal, nominal and binary categories. The data were modified so that they also varied on both the proportion of data missing and the systematization of the missing data. Two different assessments of performance were conducted: accuracy in reproducing the missing values, and predictive performance using the imputed data. Results demonstrated that the new method, Item Response Theory for Categorical Imputation (IRTCI), fared quite well compared to currently used methods, outperforming several of them in many conditions. Given the theoretical basis for the new approach, and the unique generation of probabilistic terms for determining category belonging for missing cells, IRTCI offers a viable alternative to current approaches.

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Using Machine Learning to Develop Smart Reflex Testing Protocols

Objective: Reflex testing protocols allow clinical laboratories to perform second line diagnostic tests on existing specimens based on the results of initially ordered tests. Reflex testing can support optimal clinical laboratory test ordering and diagnosis. In current clinical practice, reflex testing typically relies on simple "if-then" rules; however, this limits their scope since most test ordering decisions involve more complexity than a simple rule will allow. Here, using the analyte ferritin as an example, we propose an alternative machine learning-based approach to "smart" reflex testing with a wider scope and greater impact than traditional rule-based approaches. Methods: Using patient data, we developed a machine learning model to predict whether a patient getting CBC testing will also have ferritin testing ordered, consider applications of this model to "smart" reflex testing, and evaluate the model by comparing its performance to possible rule-based approaches. Results: Our underlying machine learning models performed moderately well in predicting ferritin test ordering and demonstrated greater suitability to reflex testing than rule-based approaches. Using chart review, we demonstrate that our model may improve ferritin test ordering. Finally, as a secondary goal, we demonstrate that ferritin test results are missing not at random (MNAR), a finding with implications for unbiased imputation of missing test results. Conclusions: Machine learning may provide a foundation for new types of reflex testing with enhanced benefits for clinical diagnosis and laboratory utilization management.

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A Comparative Study of Pretrained Language Models for Long Clinical Text

Objective: Clinical knowledge enriched transformer models (e.g., ClinicalBERT) have state-of-the-art results on clinical NLP (natural language processing) tasks. One of the core limitations of these transformer models is the substantial memory consumption due to their full self-attention mechanism, which leads to the performance degradation in long clinical texts. To overcome this, we propose to leverage long-sequence transformer models (e.g., Longformer and BigBird), which extend the maximum input sequence length from 512 to 4096, to enhance the ability to model long-term dependencies in long clinical texts. Materials and Methods: Inspired by the success of long sequence transformer models and the fact that clinical notes are mostly long, we introduce two domain enriched language models, Clinical-Longformer and Clinical-BigBird, which are pre-trained on a large-scale clinical corpus. We evaluate both language models using 10 baseline tasks including named entity recognition, question answering, natural language inference, and document classification tasks. Results: The results demonstrate that Clinical-Longformer and Clinical-BigBird consistently and significantly outperform ClinicalBERT and other short-sequence transformers in all 10 downstream tasks and achieve new state-of-the-art results. Discussion: Our pre-trained language models provide the bedrock for clinical NLP using long texts. We have made our source code available at https://github.com/luoyuanlab/Clinical-Longformer, and the pre-trained models available for public download at: https://huggingface.co/yikuan8/Clinical-Longformer. Conclusion: This study demonstrates that clinical knowledge enriched long-sequence transformers are able to learn long-term dependencies in long clinical text. Our methods can also inspire the development of other domain-enriched long-sequence transformers.

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Accelerating Iterated Persistent Homology Computations with Warm Starts

Persistent homology is a topological feature used in a variety of applications such as generating features for data analysis and penalizing optimization problems. We develop an approach to accelerate persistent homology computations performed on many similar filtered topological spaces which is based on updating associated matrix factorizations. Our approach improves the update scheme of Cohen-Steiner, Edelsbrunner, and Morozov for permutations by additionally handling addition and deletion of cells in a filtered topological space and by processing changes in a single batch. We show that the complexity of our scheme scales with the number of elementary changes to the filtration which as a result is often less expensive than the full persistent homology computation. Finally, we perform computational experiments demonstrating practical speedups in several situations including feature generation and optimization guided by persistent homology.

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Metabolomics of Aging and Alzheimer's Disease: From Single-Omics to Multi-Omics

Aging is a multifactorial process and a key factor of morbidity and mortality. Alzheimer's disease (AD) is an age-related disorder and a main cause of worldwide disability. Both aging and AD can be characterized by metabolic dysfunction. Metabolomics can quantify the complete set of metabolites in a studied sample and is helpful for studying metabolic alterations in aging and AD. In this review, we summarize the metabolomic changes regarding aging and AD, discuss their biological functions, and highlight their potential application as diagnostic biomarkers or therapeutic targets. Recent advances in multi-omics approaches for understanding the metabolic mechanism of aging and AD are also reviewed.

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AD-BERT: Using Pre-trained contextualized embeddings to Predict the Progression from Mild Cognitive Impairment to Alzheimer's Disease

Objective: We develop a deep learning framework based on the pre-trained Bidirectional Encoder Representations from Transformers (BERT) model using unstructured clinical notes from electronic health records (EHRs) to predict the risk of disease progression from Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD). Materials and Methods: We identified 3657 patients diagnosed with MCI together with their progress notes from Northwestern Medicine Enterprise Data Warehouse (NMEDW) between 2000-2020. The progress notes no later than the first MCI diagnosis were used for the prediction. We first preprocessed the notes by deidentification, cleaning and splitting, and then pretrained a BERT model for AD (AD-BERT) based on the publicly available Bio+Clinical BERT on the preprocessed notes. The embeddings of all the sections of a patient's notes processed by AD-BERT were combined by MaxPooling to compute the probability of MCI-to-AD progression. For replication, we conducted a similar set of experiments on 2563 MCI patients identified at Weill Cornell Medicine (WCM) during the same timeframe. Results: Compared with the 7 baseline models, the AD-BERT model achieved the best performance on both datasets, with Area Under receiver operating characteristic Curve (AUC) of 0.8170 and F1 score of 0.4178 on NMEDW dataset and AUC of 0.8830 and F1 score of 0.6836 on WCM dataset. Conclusion: We developed a deep learning framework using BERT models which provide an effective solution for prediction of MCI-to-AD progression using clinical note analysis.

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SHINE: SubHypergraph Inductive Neural nEtwork

Hypergraph neural networks can model multi-way connections among nodes of the graphs, which are common in real-world applications such as genetic medicine. In particular, genetic pathways or gene sets encode molecular functions driven by multiple genes, naturally represented as hyperedges. Thus, hypergraph-guided embedding can capture functional relations in learned representations. Existing hypergraph neural network models often focus on node-level or graph-level inference. There is an unmet need in learning powerful representations of subgraphs of hypergraphs in real-world applications. For example, a cancer patient can be viewed as a subgraph of genes harboring mutations in the patient, while all the genes are connected by hyperedges that correspond to pathways representing specific molecular functions. For accurate inductive subgraph prediction, we propose SubHypergraph Inductive Neural nEtwork (SHINE). SHINE uses informative genetic pathways that encode molecular functions as hyperedges to connect genes as nodes. SHINE jointly optimizes the objectives of end-to-end subgraph classification and hypergraph nodes' similarity regularization. SHINE simultaneously learns representations for both genes and pathways using strongly dual attention message passing. The learned representations are aggregated via a subgraph attention layer and used to train a multilayer perceptron for inductive subgraph inferencing. We evaluated SHINE against a wide array of state-of-the-art (hyper)graph neural networks, XGBoost, NMF and polygenic risk score models, using large scale NGS and curated datasets. SHINE outperformed all comparison models significantly, and yielded interpretable disease models with functional insights.

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Deep Learning Reveals Patterns of Diverse and Changing Sentiments Towards COVID-19 Vaccines Based on 11 Million Tweets

Over 12 billion doses of COVID-19 vaccines have been administered at the time of writing. However, public perceptions of vaccines have been complex. We analyzed COVID-19 vaccine-related tweets to understand the evolving perceptions of COVID-19 vaccines. We finetuned a deep learning classifier using a state-of-the-art model, XLNet, to detect each tweet's sentiment automatically. We employed validated methods to extract the users' race or ethnicity, gender, age, and geographical locations from user profiles. Incorporating multiple data sources, we assessed the sentiment patterns among subpopulations and juxtaposed them against vaccine uptake data to unravel their interactive patterns. 11,211,672 COVID-19 vaccine-related tweets corresponding to 2,203,681 users over two years were analyzed. The finetuned model for sentiment classification yielded an accuracy of 0.92 on testing set. Users from various demographic groups demonstrated distinct patterns in sentiments towards COVID-19 vaccines. User sentiments became more positive over time, upon which we observed subsequent upswing in the population-level vaccine uptake. Surrounding dates where positive sentiments crest, we detected encouraging news or events regarding vaccine development and distribution. Positive sentiments in pregnancy-related tweets demonstrated a delayed pattern compared with trends in general population, with postponed vaccine uptake trends. Distinctive patterns across subpopulations suggest the need of tailored strategies. Global news and events profoundly involved in shaping users' thoughts on social media. Populations with additional concerns, such as pregnancy, demonstrated more substantial hesitancy since lack of timely recommendations. Feature analysis revealed hesitancies of various subpopulations stemmed from clinical trial logics, risks and complications, and urgency of scientific evidence.

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AKI-BERT: a Pre-trained Clinical Language Model for Early Prediction of Acute Kidney Injury

Acute kidney injury (AKI) is a common clinical syndrome characterized by a sudden episode of kidney failure or kidney damage within a few hours or a few days. Accurate early prediction of AKI for patients in ICU who are more likely than others to have AKI can enable timely interventions, and reduce the complications of AKI. Much of the clinical information relevant to AKI is captured in clinical notes that are largely unstructured text and requires advanced natural language processing (NLP) for useful information extraction. On the other hand, pre-trained contextual language models such as Bidirectional Encoder Representations from Transformers (BERT) have improved performances for many NLP tasks in general domain recently. However, few have explored BERT on disease-specific medical domain tasks such as AKI early prediction. In this paper, we try to apply BERT to specific diseases and present an AKI domain-specific pre-trained language model based on BERT (AKI-BERT) that could be used to mine the clinical notes for early prediction of AKI. AKI-BERT is a BERT model pre-trained on the clinical notes of patients having risks for AKI. Our experiments on Medical Information Mart for Intensive Care III (MIMIC-III) dataset demonstrate that AKI-BERT can yield performance improvements for early AKI prediction, thus expanding the utility of the BERT model from general clinical domain to disease-specific domain.

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Clinical-Longformer and Clinical-BigBird: Transformers for long clinical sequences

Transformers-based models, such as BERT, have dramatically improved the performance for various natural language processing tasks. The clinical knowledge enriched model, namely ClinicalBERT, also achieved state-of-the-art results when performed on clinical named entity recognition and natural language inference tasks. One of the core limitations of these transformers is the substantial memory consumption due to their full self-attention mechanism. To overcome this, long sequence transformer models, e.g. Longformer and BigBird, were proposed with the idea of sparse attention mechanism to reduce the memory usage from quadratic to the sequence length to a linear scale. These models extended the maximum input sequence length from 512 to 4096, which enhanced the ability of modeling long-term dependency and consequently achieved optimal results in a variety of tasks. Inspired by the success of these long sequence transformer models, we introduce two domain enriched language models, namely Clinical-Longformer and Clinical-BigBird, which are pre-trained from large-scale clinical corpora. We evaluate both pre-trained models using 10 baseline tasks including named entity recognition, question answering, and document classification tasks. The results demonstrate that Clinical-Longformer and Clinical-BigBird consistently and significantly outperform ClinicalBERT as well as other short-sequence transformers in all downstream tasks. We have made our source code available at [https://github.com/luoyuanlab/Clinical-Longformer] the pre-trained models available for public download at: [https://huggingface.co/yikuan8/Clinical-Longformer].

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Multimodal Machine Learning in Precision Health

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.

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Machine Learning Applications in Lung Cancer Diagnosis, Treatment and Prognosis

The recent development of imaging and sequencing technologies enables systematic advances in the clinical study of lung cancer. Meanwhile, the human mind is limited in effectively handling and fully utilizing the accumulation of such enormous amounts of data. Machine learning-based approaches play a critical role in integrating and analyzing these large and complex datasets, which have extensively characterized lung cancer through the use of different perspectives from these accrued data. In this article, we provide an overview of machine learning-based approaches that strengthen the varying aspects of lung cancer diagnosis and therapy, including early detection, auxiliary diagnosis, prognosis prediction and immunotherapy practice. Moreover, we highlight the challenges and opportunities for future applications of machine learning in lung cancer.

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Distribution Preserving Graph Representation Learning

Graph neural network (GNN) is effective to model graphs for distributed representations of nodes and an entire graph. Recently, research on the expressive power of GNN attracted growing attention. A highly-expressive GNN has the ability to generate discriminative graph representations. However, in the end-to-end training process for a certain graph learning task, a highly-expressive GNN risks generating graph representations overfitting the training data for the target task, while losing information important for the model generalization. In this paper, we propose Distribution Preserving GNN (DP-GNN) - a GNN framework that can improve the generalizability of expressive GNN models by preserving several kinds of distribution information in graph representations and node representations. Besides the generalizability, by applying an expressive GNN backbone, DP-GNN can also have high expressive power. We evaluate the proposed DP-GNN framework on multiple benchmark datasets for graph classification tasks. The experimental results demonstrate that our model achieves state-of-the-art performances.

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ImageGCN: Multi-Relational Image Graph Convolutional Networks for Disease Identification with Chest X-rays

Image representation is a fundamental task in computer vision. However, most of the existing approaches for image representation ignore the relations between images and consider each input image independently. Intuitively, relations between images can help to understand the images and maintain model consistency over related images, leading to better explainability. In this paper, we consider modeling the image-level relations to generate more informative image representations, and propose ImageGCN, an end-to-end graph convolutional network framework for inductive multi-relational image modeling. We apply ImageGCN to chest X-ray images where rich relational information is available for disease identification. Unlike previous image representation models, ImageGCN learns the representation of an image using both its original pixel features and its relationship with other images. Besides learning informative representations for images, ImageGCN can also be used for object detection in a weakly supervised manner. The experimental results on 3 open-source x-ray datasets, ChestX-ray14, CheXpert and MIMIC-CXR demonstrate that ImageGCN can outperform respective baselines in both disease identification and localization tasks and can achieve comparable and often better results than the state-of-the-art methods.

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MedGCN: Medication recommendation and lab test imputation via graph convolutional networks

Laboratory testing and medication prescription are two of the most important routines in daily clinical practice. Developing an artificial intelligence system that can automatically make lab test imputations and medication recommendations can save costs on potentially redundant lab tests and inform physicians of a more effective prescription. We present an intelligent medical system (named MedGCN) that can automatically recommend the patients' medications based on their incomplete lab tests, and can even accurately estimate the lab values that have not been taken. In our system, we integrate the complex relations between multiple types of medical entities with their inherent features in a heterogeneous graph. Then we model the graph to learn a distributed representation for each entity in the graph based on graph convolutional networks (GCN). By the propagation of graph convolutional networks, the entity representations can incorporate multiple types of medical information that can benefit multiple medical tasks. Moreover, we introduce a cross regularization strategy to reduce overfitting for multi-task training by the interaction between the multiple tasks. In this study, we construct a graph to associate 4 types of medical entities, i.e., patients, encounters, lab tests, and medications, and applied a graph neural network to learn node embeddings for medication recommendation and lab test imputation. we validate our MedGCN model on two real-world datasets: NMEDW and MIMIC-III. The experimental results on both datasets demonstrate that our model can outperform the state-of-the-art in both tasks. We believe that our innovative system can provide a promising and reliable way to assist physicians to make medication prescriptions and to save costs on potentially redundant lab tests.

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Topology-Preserving Dimensionality Reduction via Interleaving Optimization

Dimensionality reduction techniques are powerful tools for data preprocessing and visualization which typically come with few guarantees concerning the topological correctness of an embedding. The interleaving distance between the persistent homology of Vietoris-Rips filtrations can be used to identify a scale at which topological features such as clusters or holes in an embedding and original data set are in correspondence. We show how optimization seeking to minimize the interleaving distance can be incorporated into dimensionality reduction algorithms, and explicitly demonstrate its use in finding an optimal linear projection. We demonstrate the utility of this framework to data visualization.

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Open-Set Recognition of Breast Cancer Treatments

Open-set recognition generalizes a classification task by classifying test samples as one of the known classes from training or "unknown." As novel cancer drug cocktails with improved treatment are continually discovered, predicting cancer treatments can naturally be formulated in terms of an open-set recognition problem. Drawbacks, due to modeling unknown samples during training, arise from straightforward implementations of prior work in healthcare open-set learning. Accordingly, we reframe the problem methodology and apply a recent existing Gaussian mixture variational autoencoder model, which achieves state-of-the-art results for image datasets, to breast cancer patient data. Not only do we obtain more accurate and robust classification results, with a 24.5% average F1 increase compared to a recent method, but we also reexamine open-set recognition in terms of deployability to a clinical setting.

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Constrained tensor factorization for computational phenotyping and mortality prediction in patients with cancer

Background: The increasing adoption of electronic health records (EHR) across the US has created troves of computable data, to which machine learning methods have been applied to extract useful insights. EHR data, represented as a three-dimensional analogue of a matrix (tensor), is decomposed into two-dimensional factors that can be interpreted as computational phenotypes. Methods: We apply constrained tensor factorization to derive computational phenotypes and predict mortality in cohorts of patients with breast, prostate, colorectal, or lung cancer in the Northwestern Medicine Enterprise Data Warehouse from 2000 to 2015. In our experiments, we examined using a supervised term in the factorization algorithm, filtering tensor co-occurrences by medical indication, and incorporating additional social determinants of health (SDOH) covariates in the factorization process. We evaluated the resulting computational phenotypes qualitatively and by assessing their ability to predict five-year mortality using the area under the curve (AUC) statistic. Results: Filtering by medical indication led to more concise and interpretable phenotypes. Mortality prediction performance (AUC) varied under the different experimental conditions and by cancer type (breast: 0.623 - 0.694, prostate: 0.603 - 0.750, colorectal: 0.523 - 0.641, and lung: 0.517 - 0.623). Generally, prediction performance improved with the use of a supervised term and the incorporation of SDOH covariates. Conclusion: Constrained tensor factorization, applied to sparse EHR data of patients with cancer, can discover computational phenotypes predictive of five-year mortality. The incorporation of SDOH variables into the factorization algorithm is an easy-to-implement and effective way to improve prediction performance.

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