Deep phenotyping of Alzheimer's disease leveraging electronic medical records identifies sex-specific clinical associations.
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ABSTRACT:
SUBMITTER: Tang AS
PROVIDER: S-EPMC8814236 | biostudies-literature | 2022 Feb
REPOSITORIES: biostudies-literature
Publications
Deep phenotyping of Alzheimer's disease leveraging electronic medical records identifies sex-specific clinical associations.
Tang Alice S AS Oskotsky Tomiko T Havaldar Shreyas S Mantyh William G WG Bicak Mesude M Solsberg Caroline Warly CW Woldemariam Sarah S Zeng Billy B Hu Zicheng Z Oskotsky Boris B Dubal Dena D Allen Isabel E IE Glicksberg Benjamin S BS Sirota Marina M
Nature communications 20220203 1
Alzheimer's Disease (AD) is a neurodegenerative disorder that is still not fully understood. Sex modifies AD vulnerability, but the reasons for this are largely unknown. We utilize two independent electronic medical record (EMR) systems across 44,288 patients to perform deep clinical phenotyping and network analysis to gain insight into clinical characteristics and sex-specific clinical associations in AD. Embeddings and network representation of patient diagnoses demonstrate greater comorbidity ...[more]
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Project description:ObjectiveElectronic Health Record (EHR) based phenotyping is a crucial yet challenging problem in the biomedical field. Though clinicians typically determine patient-level diagnoses via manual chart review, the sheer volume and heterogeneity of EHR data renders such tasks challenging, time-consuming, and prohibitively expensive, thus leading to a scarcity of clinical annotations in EHRs. Weakly supervised learning algorithms have been successfully applied to various EHR phenotyping problems, due to their ability to leverage information from large quantities of unlabeled samples to better inform predictions based on a far smaller number of patients. However, most weakly supervised methods are subject to the challenge to choose the right cutoff value to generate an optimal classifier. Furthermore, since they only utilize the most informative features (i.e., main ICD and NLP counts) they may fail for episodic phenotypes that cannot be consistently detected via ICD and NLP data. In this paper, we propose a label-efficient, weakly semi-supervised deep learning algorithm for EHR phenotyping (WSS-DL), which overcomes the limitations above.Materials and methodsWSS-DL classifies patient-level disease status through a series of learning stages: 1) generating silver standard labels, 2) deriving enhanced-silver-standard labels by fitting a weakly supervised deep learning model to data with silver standard labels as outcomes and high dimensional EHR features as input, and 3) obtaining the final prediction score and classifier by fitting a supervised learning model to data with a minimal number of gold standard labels as the outcome, and the enhanced-silver-standard labels and a minimal set of most informative EHR features as input. To assess the generalizability of WSS-DL across different phenotypes and medical institutions, we apply WSS-DL to classify a total of 17 diseases, including both acute and chronic conditions, using EHR data from three healthcare systems. Additionally, we determine the minimum quantity of training labels required by WSS-DL to outperform existing supervised and semi-supervised phenotyping methods.ResultsThe proposed method, in combining the strengths of deep learning and weakly semi-supervised learning, successfully leverages the crucial phenotyping information contained in EHR features from unlabeled samples. Indeed, the deep learning model's ability to handle high-dimensional EHR features allows it to generate strong phenotype status predictions from silver standard labels. These predictions, in turn, provide highly effective features in the final logistic regression stage, leading to high phenotyping accuracy in notably small subsets of labeled data (e.g. n = 40 labeled samples).ConclusionOur method's high performance in EHR datasets with very small numbers of labels indicates its potential value in aiding doctors to diagnose rare diseases as well as conditions susceptible to misdiagnosis.
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Project description:BackgroundDeep learning models have attracted significant interest from health care researchers during the last few decades. There have been many studies that apply deep learning to medical applications and achieve promising results. However, there are three limitations to the existing models: (1) most clinicians are unable to interpret the results from the existing models, (2) existing models cannot incorporate complicated medical domain knowledge (eg, a disease causes another disease), and (3) most existing models lack visual exploration and interaction. Both the electronic health record (EHR) data set and the deep model results are complex and abstract, which impedes clinicians from exploring and communicating with the model directly.ObjectiveThe objective of this study is to develop an interpretable and accurate risk prediction model as well as an interactive clinical prediction system to support EHR data exploration, knowledge graph demonstration, and model interpretation.MethodsA domain-knowledge-guided recurrent neural network (DG-RNN) model is proposed to predict clinical risks. The model takes medical event sequences as input and incorporates medical domain knowledge by attending to a subgraph of the whole medical knowledge graph. A global pooling operation and a fully connected layer are used to output the clinical outcomes. The middle results and the parameters of the fully connected layer are helpful in identifying which medical events cause clinical risks. DG-Viz is also designed to support EHR data exploration, knowledge graph demonstration, and model interpretation.ResultsWe conducted both risk prediction experiments and a case study on a real-world data set. A total of 554 patients with heart failure and 1662 control patients without heart failure were selected from the data set. The experimental results show that the proposed DG-RNN outperforms the state-of-the-art approaches by approximately 1.5%. The case study demonstrates how our medical physician collaborator can effectively explore the data and interpret the prediction results using DG-Viz.ConclusionsIn this study, we present DG-Viz, an interactive clinical prediction system, which brings together the power of deep learning (ie, a DG-RNN-based model) and visual analytics to predict clinical risks and visually interpret the EHR prediction results. Experimental results and a case study on heart failure risk prediction tasks demonstrate the effectiveness and usefulness of the DG-Viz system. This study will pave the way for interactive, interpretable, and accurate clinical risk predictions.
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