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This study focuses on understanding the transcriptional heterogeneity of activated platelets and its impact on diseases such as sepsis, COVID-19, and systemic lupus erythematosus (SLE). Recognizing the limited knowledge in this area, our research aims to dissect the complex transcriptional profiles of activated platelets to aid in developing targeted therapies for abnormal and pathogenic platelet subtypes. We analyzed single-cell transcriptional profiles from 47,977 platelets derived from 413 samples of patients with these diseases, utilizing Deep Neural Network (DNN) and eXtreme Gradient Boosting (XGB) to distinguish transcriptomic signatures predictive of fatal or survival outcomes. Our approach included source data annotations and platelet markers, along with SingleR and Seurat for comprehensive profiling. Additionally, we employed Uniform Manifold Approximation and Projection (UMAP) for effective dimensionality reduction and visualization, aiding in the identification of various platelet subtypes and their relation to disease severity and patient outcomes. Our results highlighted distinct platelet subpopulations that correlate with disease severity, revealing that changes in platelet transcription patterns can intensify endotheliopathy, increasing the risk of coagulation in fatal cases. Moreover, these changes may impact lymphocyte function, indicating a more extensive role for platelets in inflammatory and immune responses. This study identifies crucial biomarkers of platelet heterogeneity in serious health conditions, paving the way for innovative therapeutic approaches targeting platelet activation, which could improve patient outcomes in diseases characterized by altered platelet function.
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A new representation of disease conditions and treatment pathways accurately predicts mortality and chronic diseases
In this study, we introduce a novel representation of patient data called Disease Severity Hierarchy (DSH) that explores specific diseases and their known treatment pathways in a nested fashion to create subpopulations in a clinically meaningful way. As the DSH tree is traversed from the root towards the leaves, we encounter subpopulations that share increasing richer amounts of clinical details such as similar disease severity, illness trajectories, and time to event that are discriminative, and suitable for learning risk stratification models. The proposed DSH risk scores effectively and accurately predict the age at which a patient may be at risk of dying or developing MCE significantly better than a traditional representation of disease conditions. DSH utilizes known relationships among various entities in EHR data to capture disease severity in a natural way and has the additional benefit of being expressive and interpretable. This novel patient representation can help support critical decision making, development of smart EBP guidelines, and enhance healthcare care and disease management by helping to identify and reduce disease burden among high-risk patients.
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- Award ID(s):
- 1602394
- PAR ID:
- 10168838
- Date Published:
- Journal Name:
- AMIA 2019 Annual Symposium
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Accepted Manuscript1.0
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