Journal
CELL AND BIOSCIENCE
Volume 13, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13578-023-00991-y
Keywords
Preeclampsia risk; Machine learning; Feature selection; Marker genes; Web server
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This study developed a computational biology method using single-cell transcriptome to identify and predict pathological cell subpopulations of early-onset preeclampsia (PE). The TURF_XGB method achieved high accuracy and recall rates in classifying healthy placenta subpopulations, revealing the heterogeneity of placental biology. Additionally, the analysis revealed the involvement of dendritic cells and the role of C1QB and C1QC in mediating inflammation and driving the development of PE. The study also developed a risk stratification card for preeclampsia classification.
Background The placenta, as a unique exchange organ between mother and fetus, is essential for successful human pregnancy and fetal health. Preeclampsia (PE) caused by placental dysfunction contributes to both maternal and infant morbidity and mortality. Accurate identification of PE patients plays a vital role in the formulation of treatment plans. However, the traditional clinical methods of PE have a high misdiagnosis rate.Results Here, we first designed a computational biology method that used single-cell transcriptome (scRNA-seq) of healthy pregnancy (38 wk) and early-onset PE (28-32 wk) to identify pathological cell subpopulations and predict PE risk. Based on machine learning methods and feature selection techniques, we observed that the Tuning ReliefF (TURF) score hybrid with XGBoost (TURF_XGB) achieved optimal performance, with 92.61% accuracy and 92.46% recall for classifying nine cell subpopulations of healthy placentas. Biological landscapes of placenta heterogeneity could be mapped by the 110 marker genes screened by TURF_XGB, which revealed the superiority of the TURF feature mining. Moreover, we processed the PE dataset with LASSO to obtain 497 biomarkers. Integration analysis of the above two gene sets revealed that dendritic cells were closely associated with early-onset PE, and C1QB and C1QC might drive preeclampsia by mediating inflammation. In addition, an ensemble model-based risk stratification card was developed to classify preeclampsia patients, and its area under the receiver operating characteristic curve (AUC) could reach 0.99. For broader accessibility, we designed an accessible online web server ().Conclusion Single-cell transcriptome-based preeclampsia risk assessment using an ensemble machine learning framework is a valuable asset for clinical decision-making. C1QB and C1QC may be involved in the development and progression of early-onset PE by affecting the complement and coagulation cascades pathway that mediate inflammation, which has important implications for better understanding the pathogenesis of PE.
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