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This research addresses the issue of missing structured data in dental records by extracting diagnostic information from unstructured text. The updated periodontology classification system's complexity has increased incomplete or missing structured diagnoses. To tackle this, we use advanced AI and NLP methods, leveraging GPT-4 to generate synthetic notes for fine-tuning a RoBERTa model. This significantly enhances the model's ability to understand medical and dental language. We evaluated the model using 120 randomly selected clinical notes from two datasets, demonstrating its improved diagnostic extraction accuracy. The results showed high accuracy in diagnosing periodontal status, stage, and grade, with Site 1 scoring 0.99 and Site 2 scoring 0.98. In the subtype category, Site 2 achieved perfect scores, outperforming Site 1. This method enhances extraction accuracy and broadens its use across dental contexts. The study underscores AI and NLP's transformative impact on healthcare delivery and management. Integrating AI and NLP technologies enhances documentation and simplifies administrative tasks by precisely extracting complex clinical information. This approach effectively addresses challenges in dental diagnostics. Using synthetic training data from LLMs optimizes the training process, improving accuracy and efficiency in identifying periodontal diagnoses from clinical notes. This innovative method holds promise for broader healthcare applications, potentially improving patient care quality., Comment: 11 pages, 2 tables, 3 figures, under review

This study examines integrating EHRs and NLP with large language models (LLMs) to improve healthcare data management and patient care. It focuses on using advanced models to create secure, HIPAA-compliant synthetic patient notes for biomedical research. The study used de-identified and re-identified MIMIC III datasets with GPT-3.5, GPT-4, and Mistral 7B to generate synthetic notes. Text generation employed templates and keyword extraction for contextually relevant notes, with one-shot generation for comparison. Privacy assessment checked PHI occurrence, while text utility was tested using an ICD-9 coding task. Text quality was evaluated with ROUGE and cosine similarity metrics to measure semantic similarity with source notes. Analysis of PHI occurrence and text utility via the ICD-9 coding task showed that the keyword-based method had low risk and good performance. One-shot generation showed the highest PHI exposure and PHI co-occurrence, especially in geographic location and date categories. The Normalized One-shot method achieved the highest classification accuracy. Privacy analysis revealed a critical balance between data utility and privacy protection, influencing future data use and sharing. Re-identified data consistently outperformed de-identified data. This study demonstrates the effectiveness of keyword-based methods in generating privacy-protecting synthetic clinical notes that retain data usability, potentially transforming clinical data-sharing practices. The superior performance of re-identified over de-identified data suggests a shift towards methods that enhance utility and privacy by using dummy PHIs to perplex privacy attacks., Comment: 13 pages, 4 figures, 1 table, 1 supplementary, under review

Heterogeneous graphs can well describe the complex entity relationships in the real world. For example, online shopping networks contain multiple physical types of consumers and products, as well as multiple relationship types such as purchasing and favoriting. More and more scholars pay attention to this research because heterogeneous graph representation learning shows strong application potential in real-world scenarios. However, the existing heterogeneous graph models use data augmentation techniques to enhance the use of graph structure information, which only captures the graph structure information from the spatial topology, ignoring the information displayed in the spectrum dimension of the graph structure. To address the issue that heterogeneous graph representation learning methods fail to model spectral information, this paper introduces a spectral-enhanced graph contrastive learning model (SHCL) and proposes a spectral augmentation algorithm for the first time in heterogeneous graph neural networks. The proposed model learns an adaptive topology augmentation scheme through the heterogeneous graph itself, disrupting the structural information of the heterogeneous graph in the spectrum dimension, and ultimately improving the learning effect of the model. Experimental results on multiple real-world datasets demonstrate substantial advantages of the proposed model.

In the era of big data, access to abundant data is crucial for driving research forward. However, such data is often inaccessible due to privacy concerns or high costs, particularly in healthcare domain. Generating synthetic (tabular) data can address this, but existing models typically require substantial amounts of data to train effectively, contradicting our objective to solve data scarcity. To address this challenge, we propose a novel framework to generate synthetic tabular data, powered by large language models (LLMs) that emulates the architecture of a Generative Adversarial Network (GAN). By incorporating data generation process as contextual information and utilizing LLM as the optimizer, our approach significantly enhance the quality of synthetic data generation in common scenarios with small sample sizes. Our experimental results on public and private datasets demonstrate that our model outperforms several state-of-art models regarding generating higher quality synthetic data for downstream tasks while keeping privacy of the real data.

Summary: The vast generation of genetic data poses a significant challenge in efficiently uncovering valuable knowledge. Introducing GENEVIC, an AI-driven chat framework that tackles this challenge by bridging the gap between genetic data generation and biomedical knowledge discovery. Leveraging generative AI, notably ChatGPT, it serves as a biologist's 'copilot'. It automates the analysis, retrieval, and visualization of customized domain-specific genetic information, and integrates functionalities to generate protein interaction networks, enrich gene sets, and search scientific literature from PubMed, Google Scholar, and arXiv, making it a comprehensive tool for biomedical research. In its pilot phase, GENEVIC is assessed using a curated database that ranks genetic variants associated with Alzheimer's disease, schizophrenia, and cognition, based on their effect weights from the Polygenic Score Catalog, thus enabling researchers to prioritize genetic variants in complex diseases. GENEVIC's operation is user-friendly, accessible without any specialized training, secured by Azure OpenAI's HIPAA-compliant infrastructure, and evaluated for its efficacy through real-time query testing. As a prototype, GENEVIC is set to advance genetic research, enabling informed biomedical decisions. Availability and implementation: GENEVIC is publicly accessible at https://genevic-anath2024.streamlit.app. The underlying code is open-source and available via GitHub at https://github.com/anath2110/GENEVIC.git.

For sharing privacy-sensitive data, de-identification is commonly regarded as adequate for safeguarding privacy. Synthetic data is also being considered as a privacy-preserving alternative. Recent successes with numerical and tabular data generative models and the breakthroughs in large generative language models raise the question of whether synthetically generated clinical notes could be a viable alternative to real notes for research purposes. In this work, we demonstrated that (i) de-identification of real clinical notes does not protect records against a membership inference attack, (ii) proposed a novel approach to generate synthetic clinical notes using the current state-of-the-art large language models, (iii) evaluated the performance of the synthetically generated notes in a clinical domain task, and (iv) proposed a way to mount a membership inference attack where the target model is trained with synthetic data. We observed that when synthetically generated notes closely match the performance of real data, they also exhibit similar privacy concerns to the real data. Whether other approaches to synthetically generated clinical notes could offer better trade-offs and become a better alternative to sensitive real notes warrants further investigation.

This study explored the usability of prompt generation on named entity recognition (NER) tasks and the performance in different settings of the prompt. The prompt generation by GPT-J models was utilized to directly test the gold standard as well as to generate the seed and further fed to the RoBERTa model with the spaCy package. In the direct test, a lower ratio of negative examples with higher numbers of examples in prompt achieved the best results with a F1 score of 0.72. The performance revealed consistency, 0.92-0.97 in the F1 score, in all settings after training with the RoBERTa model. The study highlighted the importance of seed quality rather than quantity in feeding NER models. This research reports on an efficient and accurate way to mine clinical notes for periodontal diagnoses, allowing researchers to easily and quickly build a NER model with the prompt generation approach., Comment: 2023 AMIA Annual Symposium, see https://amia.org/education-events/amia-2023-annual-symposium

This study aimed to utilize text processing and natural language processing (NLP) models to mine clinical notes for the diagnosis of periodontitis and to evaluate the performance of a named entity recognition (NER) model on different regular expression (RE) methods. Two complexity levels of RE methods were used to extract and generate the training data. The SpaCy package and RoBERTa transformer models were used to build the NER model and evaluate its performance with the manual-labeled gold standards. The comparison of the RE methods with the gold standard showed that as the complexity increased in the RE algorithms, the F1 score increased from 0.3-0.4 to around 0.9. The NER models demonstrated excellent predictions, with the simple RE method showing 0.84-0.92 in the evaluation metrics, and the advanced and combined RE method demonstrating 0.95-0.99 in the evaluation. This study provided an example of the benefit of combining NER methods and NLP models in extracting target information from free-text to structured data and fulfilling the need for missing diagnoses from unstructured notes., Comment: IEEE ICHI 2023, see https://ieeeichi.github.io/ICHI2023/program.html

Liver transplantation often faces fairness challenges across subgroups defined by sensitive attributes such as age group, gender, and race/ethnicity. Machine learning models for outcome prediction can introduce additional biases. Therefore, we introduce Fairness through the Equitable Rate of Improvement in Multitask Learning (FERI) algorithm for fair predictions of graft failure risk in liver transplant patients. FERI constrains subgroup loss by balancing learning rates and preventing subgroup dominance in the training process. Our results show that FERI maintained high predictive accuracy with AUROC and AUPRC comparable to baseline models. More importantly, FERI demonstrated an ability to improve fairness without sacrificing accuracy. Specifically, for the gender, FERI reduced the demographic parity disparity by 71.74%, and for the age group, it decreased the equalized odds disparity by 40.46%. Therefore, the FERI algorithm advanced fairness-aware predictive modeling in healthcare and provides an invaluable tool for equitable healthcare systems., Comment: First Prize Student Award Paper, American Medical Informatics Association 2024 Informatics Summit

The exponential growth in scholarly publications necessitates advanced tools for efficient article retrieval, especially in interdisciplinary fields where diverse terminologies are used to describe similar research. Traditional keyword-based search engines often fall short in assisting users who may not be familiar with specific terminologies. To address this, we present a knowledge graph-based paper search engine for biomedical research to enhance the user experience in discovering relevant queries and articles. The system, dubbed DiscoverPath, employs Named Entity Recognition (NER) and part-of-speech (POS) tagging to extract terminologies and relationships from article abstracts to create a KG. To reduce information overload, DiscoverPath presents users with a focused subgraph containing the queried entity and its neighboring nodes and incorporates a query recommendation system, enabling users to iteratively refine their queries. The system is equipped with an accessible Graphical User Interface that provides an intuitive visualization of the KG, query recommendations, and detailed article information, enabling efficient article retrieval, thus fostering interdisciplinary knowledge exploration. DiscoverPath is open-sourced at https://github.com/ynchuang/DiscoverPath.

Deep learning continues to rapidly evolve and is now demonstrating remarkable potential for numerous medical prediction tasks. However, realizing deep learning models that generalize across healthcare organizations is challenging. This is due, in part, to the inherent siloed nature of these organizations and patient privacy requirements. To address this problem, we illustrate how split learning can enable collaborative training of deep learning models across disparate and privately maintained health datasets, while keeping the original records and model parameters private. We introduce a new privacy-preserving distributed learning framework that offers a higher level of privacy compared to conventional federated learning. We use several biomedical imaging and electronic health record (EHR) datasets to show that deep learning models trained via split learning can achieve highly similar performance to their centralized and federated counterparts while greatly improving computational efficiency and reducing privacy risks.

Learning about diagnostic features and related clinical information from dental radiographs is important for dental research. However, the lack of expert-annotated data and convenient search tools poses challenges. Our primary objective is to design a search tool that uses a user's query for oral-related research. The proposed framework, Contrastive LAnguage Image REtrieval Search for dental research, Dental CLAIRES, utilizes periapical radiographs and associated clinical details such as periodontal diagnosis, demographic information to retrieve the best-matched images based on the text query. We applied a contrastive representation learning method to find images described by the user's text by maximizing the similarity score of positive pairs (true pairs) and minimizing the score of negative pairs (random pairs). Our model achieved a hit@3 ratio of 96% and a Mean Reciprocal Rank (MRR) of 0.82. We also designed a graphical user interface that allows researchers to verify the model's performance with interactions., Comment: 10 pages, 7 figures, 4 tables

In the era of big data, there is an increasing need for healthcare providers, communities, and researchers to share data and collaborate to improve health outcomes, generate valuable insights, and advance research. The Health Insurance Portability and Accountability Act of 1996 (HIPAA) is a federal law designed to protect sensitive health information by defining regulations for protected health information (PHI). However, it does not provide efficient tools for detecting or removing PHI before data sharing. One of the challenges in this area of research is the heterogeneous nature of PHI fields in data across different parties. This variability makes rule-based sensitive variable identification systems that work on one database fail on another. To address this issue, our paper explores the use of machine learning algorithms to identify sensitive variables in structured data, thus facilitating the de-identification process. We made a key observation that the distributions of metadata of PHI fields and non-PHI fields are very different. Based on this novel finding, we engineered over 30 features from the metadata of the original features and used machine learning to build classification models to automatically identify PHI fields in structured Electronic Health Record (EHR) data. We trained the model on a variety of large EHR databases from different data sources and found that our algorithm achieves 99% accuracy when detecting PHI-related fields for unseen datasets. The implications of our study are significant and can benefit industries that handle sensitive data., Comment: Add fugire axis label

Multiple Sclerosis (MS) is a chronic disease developed in human brain and spinal cord, which can cause permanent damage or deterioration of the nerves. The severity of MS disease is monitored by the Expanded Disability Status Scale (EDSS), composed of several functional sub-scores. Early and accurate classification of MS disease severity is critical for slowing down or preventing disease progression via applying early therapeutic intervention strategies. Recent advances in deep learning and the wide use of Electronic Health Records (EHR) creates opportunities to apply data-driven and predictive modeling tools for this goal. Previous studies focusing on using single-modal machine learning and deep learning algorithms were limited in terms of prediction accuracy due to the data insufficiency or model simplicity. In this paper, we proposed an idea of using patients' multimodal longitudinal and longitudinal EHR data to predict multiple sclerosis disease severity at the hospital visit. This work has two important contributions. First, we describe a pilot effort to leverage structured EHR data, neuroimaging data and clinical notes to build a multi-modal deep learning framework to predict patient's MS disease severity. The proposed pipeline demonstrates up to 25% increase in terms of the area under the Area Under the Receiver Operating Characteristic curve (AUROC) compared to models using single-modal data. Second, the study also provides insights regarding the amount useful signal embedded in each data modality with respect to MS disease prediction, which may improve data collection processes.

Liver transplantation is a life-saving procedure for patients with end-stage liver disease. There are two main challenges in liver transplant: finding the best matching patient for a donor and ensuring transplant equity among different subpopulations. The current MELD scoring system evaluates a patient's mortality risk if not receiving an organ within 90 days. However, the donor-patient matching should also consider post-transplant risk factors, such as cardiovascular disease, chronic rejection, etc., which are all common complications after transplant. Accurate prediction of these risk scores remains a significant challenge. In this study, we used predictive models to solve the above challenges. Specifically, we proposed a deep-learning model to predict multiple risk factors after a liver transplant. By formulating it as a multi-task learning problem, the proposed deep neural network was trained to simultaneously predict the five post-transplant risks and achieve equal good performance by exploiting task-balancing techniques. We also proposed a novel fairness-achieving algorithm to ensure prediction fairness across different subpopulations. We used electronic health records of 160,360 liver transplant patients, including demographic information, clinical variables, and laboratory values, collected from the liver transplant records of the United States from 1987 to 2018. The model's performance was evaluated using various performance metrics such as AUROC and AUPRC. Our experiment results highlighted the success of our multitask model in achieving task balance while maintaining accuracy. The model significantly reduced the task discrepancy by 39%. Further application of the fairness-achieving algorithm substantially reduced fairness disparity among all sensitive attributes (gender, age group, and race/ethnicity) in each risk factor., Comment: Published in Journal of Biomedical Informatics

Organ transplant is the essential treatment method for some end-stage diseases, such as liver failure. Analyzing the post-transplant cause of death (CoD) after organ transplant provides a powerful tool for clinical decision making, including personalized treatment and organ allocation. However, traditional methods like Model for End-stage Liver Disease (MELD) score and conventional machine learning (ML) methods are limited in CoD analysis due to two major data and model-related challenges. To address this, we propose a novel framework called CoD-MTL leveraging multi-task learning to model the semantic relationships between various CoD prediction tasks jointly. Specifically, we develop a novel tree distillation strategy for multi-task learning, which combines the strength of both the tree model and multi-task learning. Experimental results are presented to show the precise and reliable CoD predictions of our framework. A case study is conducted to demonstrate the clinical importance of our method in the liver transplant., Comment: AMIA Annual Symposium 2023 Best Student Paper Finalist

Objective: This study quantifies the capabilities of GPT-3.5 and GPT-4 for clinical named entity recognition (NER) tasks and proposes task-specific prompts to improve their performance. Materials and Methods: We evaluated these models on two clinical NER tasks: (1) to extract medical problems, treatments, and tests from clinical notes in the MTSamples corpus, following the 2010 i2b2 concept extraction shared task, and (2) identifying nervous system disorder-related adverse events from safety reports in the vaccine adverse event reporting system (VAERS). To improve the GPT models' performance, we developed a clinical task-specific prompt framework that includes (1) baseline prompts with task description and format specification, (2) annotation guideline-based prompts, (3) error analysis-based instructions, and (4) annotated samples for few-shot learning. We assessed each prompt's effectiveness and compared the models to BioClinicalBERT. Results: Using baseline prompts, GPT-3.5 and GPT-4 achieved relaxed F1 scores of 0.634, 0.804 for MTSamples, and 0.301, 0.593 for VAERS. Additional prompt components consistently improved model performance. When all four components were used, GPT-3.5 and GPT-4 achieved relaxed F1 socres of 0.794, 0.861 for MTSamples and 0.676, 0.736 for VAERS, demonstrating the effectiveness of our prompt framework. Although these results trail BioClinicalBERT (F1 of 0.901 for the MTSamples dataset and 0.802 for the VAERS), it is very promising considering few training samples are needed. Conclusion: While direct application of GPT models to clinical NER tasks falls short of optimal performance, our task-specific prompt framework, incorporating medical knowledge and training samples, significantly enhances GPT models' feasibility for potential clinical applications., Comment: 17 pages, 5 tables, 6 figure

The process of matching patients with suitable clinical trials is essential for advancing medical research and providing optimal care. However, current approaches face challenges such as data standardization, ethical considerations, and a lack of interoperability between Electronic Health Records (EHRs) and clinical trial criteria. In this paper, we explore the potential of large language models (LLMs) to address these challenges by leveraging their advanced natural language generation capabilities to improve compatibility between EHRs and clinical trial descriptions. We propose an innovative privacy-aware data augmentation approach for LLM-based patient-trial matching (LLM-PTM), which balances the benefits of LLMs while ensuring the security and confidentiality of sensitive patient data. Our experiments demonstrate a 7.32% average improvement in performance using the proposed LLM-PTM method, and the generalizability to new data is improved by 12.12%. Additionally, we present case studies to further illustrate the effectiveness of our approach and provide a deeper understanding of its underlying principles.

Electronic health records (EHRs) store an extensive array of patient information, encompassing medical histories, diagnoses, treatments, and test outcomes. These records are crucial for enabling healthcare providers to make well-informed decisions regarding patient care. Summarizing clinical notes further assists healthcare professionals in pinpointing potential health risks and making better-informed decisions. This process contributes to reducing errors and enhancing patient outcomes by ensuring providers have access to the most pertinent and current patient data. Recent research has shown that incorporating prompts with large language models (LLMs) substantially boosts the efficacy of summarization tasks. However, we show that this approach also leads to increased output variance, resulting in notably divergent outputs even when prompts share similar meanings. To tackle this challenge, we introduce a model-agnostic Soft Prompt-Based Calibration (SPeC) pipeline that employs soft prompts to diminish variance while preserving the advantages of prompt-based summarization. Experimental findings on multiple clinical note tasks and LLMs indicate that our method not only bolsters performance but also effectively curbs variance for various LLMs, providing a more uniform and dependable solution for summarizing vital medical information.

Clinical trials are indispensable in developing new treatments, but they face obstacles in patient recruitment and retention, hindering the enrollment of necessary participants. To tackle these challenges, deep learning frameworks have been created to match patients to trials. These frameworks calculate the similarity between patients and clinical trial eligibility criteria, considering the discrepancy between inclusion and exclusion criteria. Recent studies have shown that these frameworks outperform earlier approaches. However, deep learning models may raise fairness issues in patient-trial matching when certain sensitive groups of individuals are underrepresented in clinical trials, leading to incomplete or inaccurate data and potential harm. To tackle the issue of fairness, this work proposes a fair patient-trial matching framework by generating a patient-criterion level fairness constraint. The proposed framework considers the inconsistency between the embedding of inclusion and exclusion criteria among patients of different sensitive groups. The experimental results on real-world patient-trial and patient-criterion matching tasks demonstrate that the proposed framework can successfully alleviate the predictions that tend to be biased.

Recent advancements in large language models (LLMs) have led to the development of highly potent models like OpenAI's ChatGPT. These models have exhibited exceptional performance in a variety of tasks, such as question answering, essay composition, and code generation. However, their effectiveness in the healthcare sector remains uncertain. In this study, we seek to investigate the potential of ChatGPT to aid in clinical text mining by examining its ability to extract structured information from unstructured healthcare texts, with a focus on biological named entity recognition and relation extraction. However, our preliminary results indicate that employing ChatGPT directly for these tasks resulted in poor performance and raised privacy concerns associated with uploading patients' information to the ChatGPT API. To overcome these limitations, we propose a new training paradigm that involves generating a vast quantity of high-quality synthetic data with labels utilizing ChatGPT and fine-tuning a local model for the downstream task. Our method has resulted in significant improvements in the performance of downstream tasks, improving the F1-score from 23.37% to 63.99% for the named entity recognition task and from 75.86% to 83.59% for the relation extraction task. Furthermore, generating data using ChatGPT can significantly reduce the time and effort required for data collection and labeling, as well as mitigate data privacy concerns. In summary, the proposed framework presents a promising solution to enhance the applicability of LLM models to clinical text mining., Comment: 10 pages, 8 tables, 4 figures

Liver transplant is an essential therapy performed for severe liver diseases. The fact of scarce liver resources makes the organ assigning crucial. Model for End-stage Liver Disease (MELD) score is a widely adopted criterion when making organ distribution decisions. However, it ignores post-transplant outcomes and organ/donor features. These limitations motivate the emergence of machine learning (ML) models. Unfortunately, ML models could be unfair and trigger bias against certain groups of people. To tackle this problem, this work proposes a fair machine learning framework targeting graft failure prediction in liver transplant. Specifically, knowledge distillation is employed to handle dense and sparse features by combining the advantages of tree models and neural networks. A two-step debiasing method is tailored for this framework to enhance fairness. Experiments are conducted to analyze unfairness issues in existing models and demonstrate the superiority of our method in both prediction and fairness performance., Comment: AMIA Symposium 2022 Best Student Paper Finalist

Social determinants of health (SDoH) have a significant impact on health outcomes and well-being. Addressing SDoH is the key to reducing healthcare inequalities and transforming a "sick care" system into a "health promoting" system. To address the SDOH terminology gap and better embed relevant elements in advanced biomedical informatics, we propose an SDoH ontology (SDoHO), which represents fundamental SDoH factors and their relationships in a standardized and measurable way. The ontology formally models classes, relationships, and constraints based on multiple SDoH-related resources. Expert review and coverage evaluation, using clinical notes data and a national survey, showed satisfactory results. SDoHO could potentially play an essential role in providing a foundation for a comprehensive understanding of the associations between SDoH and health outcomes and providing a path toward health equity across populations., Comment: J Am Med Inform Assoc Published Online First: 10 June 2023

Deep learning models trained on large-scale data have achieved encouraging performance in many real-world tasks. Meanwhile, publishing those models trained on sensitive datasets, such as medical records, could pose serious privacy concerns. To counter these issues, one of the current state-of-the-art approaches is the Private Aggregation of Teacher Ensembles, or PATE, which achieved promising results in preserving the utility of the model while providing a strong privacy guarantee. PATE combines an ensemble of "teacher models" trained on sensitive data and transfers the knowledge to a "student" model through the noisy aggregation of teachers' votes for labeling unlabeled public data which the student model will be trained on. However, the knowledge or voted labels learned by the student are noisy due to private aggregation. Learning directly from noisy labels can significantly impact the accuracy of the student model. In this paper, we propose the PATE++ mechanism, which combines the current advanced noisy label training mechanisms with the original PATE framework to enhance its accuracy. A novel structure of Generative Adversarial Nets (GANs) is developed in order to integrate them effectively. In addition, we develop a novel noisy label detection mechanism for semi-supervised model training to further improve student model performance when training with noisy labels. We evaluate our method on Fashion-MNIST and SVHN to show the improvements on the original PATE on all measures.

As the sequencing costs are decreasing, there is great incentive to perform large scale association studies to increase power of detecting new variants. Federated association testing among different institutions is a viable solution for increasing sample sizes by sharing the intermediate testing statistics that are aggregated by a central server. There are, however, standing challenges to performing federated association testing. Association tests are known to be confounded by numerous factors such as population stratification, which can be especially important in multiancestral studies and in admixed populations among different sites. Furthermore, disease etiology should be considered via flexible models to avoid biases in the significance of the genetic effect. A rising challenge for performing large scale association studies is the privacy of participants and related ethical concerns of stigmatization and marginalization. Here, we present dMEGA, a flexible and efficient method for performing federated generalized linear mixed model based association testing among multiple sites while underlying genotype and phenotype data are not explicitly shared. dMEGA first utilizes a reference projection to estimate population-based covariates without sharing genotype dataset among sites. Next, dMEGA uses Laplacian approximation for the parameter likelihoods and decomposes parameter estimation into efficient local-gradient updates among sites. We use simulated and real datasets to demonstrate the accuracy and efficiency of dMEGA. Overall, dMEGA's formulation is flexible to integrate fixed and random effects in a federated setting.

Tensor factorization has received increasing interest due to its intrinsic ability to capture latent factors in multi-dimensional data with many applications such as recommender systems and Electronic Health Records (EHR) mining. PARAFAC2 and its variants have been proposed to address irregular tensors where one of the tensor modes is not aligned, e.g., different users in recommender systems or patients in EHRs may have different length of records. PARAFAC2 has been successfully applied on EHRs for extracting meaningful medical concepts (phenotypes). Despite recent advancements, current models' predictability and interpretability are not satisfactory, which limits its utility for downstream analysis. In this paper, we propose MULTIPAR: a supervised irregular tensor factorization with multi-task learning. MULTIPAR is flexible to incorporate both static (e.g. in-hospital mortality prediction) and continuous or dynamic (e.g. the need for ventilation) tasks. By supervising the tensor factorization with downstream prediction tasks and leveraging information from multiple related predictive tasks, MULTIPAR can yield not only more meaningful phenotypes but also better predictive performance for downstream tasks. We conduct extensive experiments on two real-world temporal EHR datasets to demonstrate that MULTIPAR is scalable and achieves better tensor fit with more meaningful subgroups and stronger predictive performance compared to existing state-of-the-art methods.

With the reduction of sequencing costs and the pervasiveness of computing devices, genomic data collection is continually growing. However, data collection is highly fragmented and the data is still siloed across different repositories. Analyzing all of this data would be transformative for genomics research. However, the data is sensitive, and therefore cannot be easily centralized. Furthermore, there may be correlations in the data, which if not detected, can impact the analysis. In this paper, we take the first step towards identifying correlated records across multiple data repositories in a privacy-preserving manner. The proposed framework, based on random shuffling, synthetic record generation, and local differential privacy, allows a trade-off of accuracy and computational efficiency. An extensive evaluation on real genomic data from the OpenSNP dataset shows that the proposed solution is efficient and effective., Comment: 10 pages, 3 figures

Causal structure learning refers to a process of identifying causal structures from observational data, and it can have multiple applications in biomedicine and health care. This paper provides a practical review and tutorial on scalable causal structure learning models with examples of real-world data to help health care audiences understand and apply them. We reviewed traditional (combinatorial and score-based methods) for causal structure discovery and machine learning-based schemes. We also highlighted recent developments in biomedicine where causal structure learning can be applied to discover structures such as gene networks, brain connectivity networks, and those in cancer epidemiology. We also compared the performance of traditional and machine learning-based algorithms for causal discovery over some benchmark data sets. Machine learning-based approaches, including deep learning, have many advantages over traditional approaches, such as scalability, including a greater number of variables, and potentially being applied in a wide range of biomedical applications, such as genetics, if sufficient data are available. Furthermore, these models are more flexible than traditional models and are poised to positively affect many applications in the future.

Objectives: This paper develops two algorithms to achieve federated generalized linear mixed effect models (GLMM), and compares the developed model's outcomes with each other, as well as that from the standard R package (`lme4'). Methods: The log-likelihood function of GLMM is approximated by two numerical methods (Laplace approximation and Gaussian Hermite approximation), which supports federated decomposition of GLMM to bring computation to data. Results: Our developed method can handle GLMM to accommodate hierarchical data with multiple non-independent levels of observations in a federated setting. The experiment results demonstrate comparable (Laplace) and superior (Gaussian-Hermite) performances with simulated and real-world data. Conclusion: We developed and compared federated GLMMs with different approximations, which can support researchers in analyzing biomedical data to accommodate mixed effects and address non-independence due to hierarchical structures (i.e., institutes, region, country, etc.)., Comment: 19 pages, 5 figures, submitted to Journal of Biomedical Informatics

Developing new drugs for target diseases is a time-consuming and expensive task, drug repurposing has become a popular topic in the drug development field. As much health claim data become available, many studies have been conducted on the data. The real-world data is noisy, sparse, and has many confounding factors. In addition, many studies have shown that drugs effects are heterogeneous among the population. Lots of advanced machine learning models about estimating heterogeneous treatment effects (HTE) have emerged in recent years, and have been applied to in econometrics and machine learning communities. These studies acknowledge medicine and drug development as the main application area, but there has been limited translational research from the HTE methodology to drug development. We aim to introduce the HTE methodology to the healthcare area and provide feasibility consideration when translating the methodology with benchmark experiments on healthcare administrative claim data. Also, we want to use benchmark experiments to show how to interpret and evaluate the model when it is applied to healthcare research. By introducing the recent HTE techniques to a broad readership in biomedical informatics communities, we expect to promote the wide adoption of causal inference using machine learning. We also expect to provide the feasibility of HTE for personalized drug effectiveness., Comment: 52 pages, 8 figures

Abstract: Aim: The goal was to use a Deep Convolutional Neural Network to measure the radiographic alveolar bone level to aid periodontal diagnosis. Material and methods: A Deep Learning (DL) model was developed by integrating three segmentation networks (bone area, tooth, cementoenamel junction) and image analysis to measure the radiographic bone level and assign radiographic bone loss (RBL) stages. The percentage of RBL was calculated to determine the stage of RBL for each tooth. A provisional periodontal diagnosis was assigned using the 2018 periodontitis classification. RBL percentage, staging, and presumptive diagnosis were compared to the measurements and diagnoses made by the independent examiners. Results: The average Dice Similarity Coefficient (DSC) for segmentation was over 0.91. There was no significant difference in RBL percentage measurements determined by DL and examiners (p=0.65). The Area Under the Receiver Operating Characteristics Curve of RBL stage assignment for stage I, II and III was 0.89, 0.90 and 0.90, respectively. The accuracy of the case diagnosis was 0.85. Conclusion: The proposed DL model provides reliable RBL measurements and image-based periodontal diagnosis using periapical radiographic images. However, this model has to be further optimized and validated by a larger number of images to facilitate its application., Comment: Word count: 3485; Number of figures: 4; tables: 2; references: 34

The PC algorithm is the state-of-the-art algorithm for causal structure discovery on observational data. It can be computationally expensive in the worst case due to the conditional independence tests are performed in an exhaustive-searching manner. This makes the algorithm computationally intractable when the task contains several hundred or thousand nodes, particularly when the true underlying causal graph is dense. We propose a critical observation that the conditional set rendering two nodes independent is non-unique, and including certain redundant nodes do not sacrifice result accuracy. Based on this finding, the innovations of our work are two-folds. First, we innovate on a reserve order linkage pruning PC algorithm which significantly increases the algorithm's efficiency. Second, we propose a parallel computing strategy for statistical independence tests by leveraging tensor computation, which brings further speedup. We also prove the proposed algorithm does not induce statistical power loss under mild graph and data dimensionality assumptions. Experimental results show that the single-threaded version of the proposed algorithm can achieve a 6-fold speedup compared to the PC algorithm on a dense 95-node graph, and the parallel version can make a 825-fold speed-up. We also provide proof that the proposed algorithm is consistent under the same set of conditions with conventional PC algorithm., Comment: 37 pages

In this work, we propose a novel problem formulation for de-identification of unstructured clinical text. We formulate the de-identification problem as a sequence to sequence learning problem instead of a token classification problem. Our approach is inspired by the recent state-of -the-art performance of sequence to sequence learning models for named entity recognition. Early experimentation of our proposed approach achieved 98.91% recall rate on i2b2 dataset. This performance is comparable to current state-of-the-art models for unstructured clinical text de-identification., Comment: Accepted in Poster Track for ACM CCS 2021