Residual facial erythema in atopic dermatitis patients treated with dupilumab stratified by machine learning.

BACKGROUND: Persistent facial erythema represents a significant complication in atopic dermatitis (AD) patients undergoing treatment with dupilumab. Stratifying patients based on the erythema course is crucial for elucidating heterogeneous phenotypes and facilitating advanced drug efficacy predictions. OBJECTIVES: This study aimed to identify factors associated with facial erythema severity in dupilumab-treated AD patients and to establish a prediction model for drug response based on the identified factors. METHODS: Data from a retrospective study conducted between July 2018 and July 2021 were collected and analysed. Patients were categorized into three groups via hierarchical clustering based on the course of facial erythema: early remission, low remission and persistent residual. LightGBM, a supervised gradient boosting decision tree algorithm, was employed to discern group differences and construct a prediction model. The model incorporated patient demographic and clinical profiles, including pre- and post-treatment examinations. The model's performance was evaluated using accuracy and the area under the receiver operating characteristic curve (AUC). RESULTS: The binary classification model demonstrated an accuracy of 89.10% and an AUC of 0.862 when distinguishing between early remission and persistent residual patients. The eight prominent factors associated with facial erythema severity included age, sex, lactate dehydrogenase (LDH), immunoglobulin E (IgE), eosinophil count, white blood cell count, Alnus allergy and cedar allergy. CONCLUSIONS: This study has two main significances: first, three clusters were identified through unsupervised learning; second, a classification model was constructed that proved more accurate than random prediction. The stratification and identification of crucial factors associated with residual facial erythema in dupilumab-treated AD patients lay the foundation for AI-powered prognostic models. This groundwork provides a substantial basis for enhancing future medical AI support in AD treatment selection, potentially improving personalized treatment approaches and outcomes.

Best practices for multimodal clinical data management and integration: An atopic dermatitis research case.

BACKGROUND: In clinical research on multifactorial diseases such as atopic dermatitis, data-driven medical research has become more widely used as means to clarify diverse pathological conditions and to realize precision medicine. However, modern clinical data, characterized as large-scale, multimodal, and multi-center, causes difficulties in data integration and management, which limits productivity in clinical data science. METHODS: We designed a generic data management flow to collect, cleanse, and integrate data to handle different types of data generated at multiple institutions by 10 types of clinical studies. We developed MeDIA (Medical Data Integration Assistant), a software to browse the data in an integrated manner and extract subsets for analysis. RESULTS: MeDIA integrates and visualizes data and information on research participants obtained from multiple studies. It then provides a sophisticated interface that supports data management and helps data scientists retrieve the data sets they need. Furthermore, the system promotes the use of unified terms such as identifiers or sampling dates to reduce the cost of pre-processing by data analysts. We also propose best practices in clinical data management flow, which we learned from the development and implementation of MeDIA. CONCLUSIONS: The MeDIA system solves the problem of multimodal clinical data integration, from complex text data such as medical records to big data such as omics data from a large number of patients. The system and the proposed best practices can be applied not only to allergic diseases but also to other diseases to promote data-driven medical research.

Multifaceted analysis of cross-tissue transcriptomes reveals phenotype-endotype associations in atopic dermatitis.

Atopic dermatitis (AD) is a skin disease that is heterogeneous both in terms of clinical manifestations and molecular profiles. It is increasingly recognized that AD is a systemic rather than a local disease and should be assessed in the context of whole-body pathophysiology. Here we show, via integrated RNA-sequencing of skin tissue and peripheral blood mononuclear cell (PBMC) samples along with clinical data from 115 AD patients and 14 matched healthy controls, that specific clinical presentations associate with matching differential molecular signatures. We establish a regression model based on transcriptome modules identified in weighted gene co-expression network analysis to extract molecular features associated with detailed clinical phenotypes of AD. The two main, qualitatively differential skin manifestations of AD, erythema and papulation are distinguished by differential immunological signatures. We further apply the regression model to a longitudinal dataset of 30 AD patients for personalized monitoring, highlighting patient heterogeneity in disease trajectories. The longitudinal features of blood tests and PBMC transcriptome modules identify three patient clusters which are aligned with clinical severity and reflect treatment history. Our approach thus serves as a framework for effective clinical investigation to gain a holistic view on the pathophysiology of complex human diseases.

Multiomics Investigation Revealing the Characteristics of HIV-1-Infected Cells In Vivo.

For eradication of HIV-1 infection, it is important to elucidate the detailed features and heterogeneity of HIV-1-infected cells in vivo. To reveal multiple characteristics of HIV-1-producing cells in vivo, we use a hematopoietic-stem-cell-transplanted humanized mouse model infected with GFP-encoding replication-competent HIV-1. We perform multiomics experiments using recently developed technology to identify the features of HIV-1-infected cells. Genome-wide HIV-1 integration-site analysis reveals that productive HIV-1 infection tends to occur in cells with viral integration into transcriptionally active genomic regions. Bulk transcriptome analysis reveals that a high level of viral mRNA is transcribed in HIV-1-infected cells. Moreover, single-cell transcriptome analysis shows the heterogeneity of HIV-1-infected cells, including CXCL13high cells and a subpopulation with low expression of interferon-stimulated genes, which can contribute to efficient viral spread in vivo. Our findings describe multiple characteristics of HIV-1-producing cells in vivo, which could provide clues for the development of an HIV-1 cure.