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Su, E. C.-Y.

Publications and source records attributed to Su, E. C.-Y..

2 recordsLinked to original sources

rplec: An R package of placental epigenetic clock to estimate aging by DNA-methylation-based gestational age

BackgroundLatest placental epigenetic clocks (PlECs) were claimed to be robust when applied to cases with either maternal or fetal adverse conditions. However, the accuracies in estimating gestational age (GA) were lower in earlier trimesters. We have developed a multistage predictive model to improve the accuracies, but it resulted in a large and complex PlEC, which may be less usable for non-computational scientists. To improve the usability of our PlEC, we aimed to develop an R package of PlEC to estimate aging by DNA-methylation-based GA (DNAm-GA). MethodsAn R package was developed to simplify our scikit-learn models into a single function and to utilize DNAm-GA for placental aging study. We provided two functions to normalize DNA methylation values and estimate DNAm-GA. Both were designed to run such that a user can adjust the number of samples per batch to fit their computational resources. Our model was simplified into a simple additive operation to reduce the need for expensive computation. Furthermore, two functions to perform quality control and identify placental aging. Quality control is performed by root mean squared-error (RMSE), mean absolute difference, and correlation coefficient. We defined placental aging as the deviation of placental DNAm-GA from the true GA beyond that from the measurement error. ResultsThe simplified version of PlEC achieved similar performance with the original scikit-learn model with RMSE 0.102 (95% CI 0.101, 0.104), which was reasonably imperfect since Python and R handle floating/decimal numbers, differently. In our use case example, we could observe significant difference of placental aging in a specific period between case and control. ConclusionsOur R package could reduce the computational requirement to use our models and maintained the precision in estimating DNAm-GA and our analytical framework could utilize DNAm-GA for placental aging study. Our PlEC also allows individual assessment of placental aging in clinical settings via the residual DNAm-GA.

bioinformatics↗

Low- and high-level information analyses of transcriptome connecting endometrial-decidua-placental origin of preeclampsia subtypes: A preliminary study

BackgroundExisting proposed pathogenesis for preeclampsia (PE) was only applied for early onset subtype and did not consider pre-pregnancy and competing risks. We aimed to decipher PE subtypes by identifying related transcriptome that represents endometrial maturation and histologic chorioamnionitis. MethodsWe utilized eight arrays of mRNA expression for discovery (n=289), and other eight arrays for validation (n=352). Differentially expressed genes (DEGs) were overlapped between those of: (1) healthy samples from endometrium, decidua, and placenta, and placenta samples under histologic chorioamnionitis; and (2) placenta samples for each of the subtypes. They were all possible combinations based on four axes: (1) pregnancy-induced hypertension; (2) placental dysfunction-related diseases (e.g., fetal growth restriction [FGR]); (3) onset; and (4) severity. ResultsThe DEGs of endometrium at late-secretory phase, but none of decidua, significantly overlapped with those of any subtypes with: (1) early onset (p-values [≤]0.008); (2) severe hypertension and proteinuria (p-values [≤]0.042); or (3) chronic hypertension and/or severe PE with FGR (p-values [≤]0.042). Although sharing the same subtypes whose DEGs with which significantly overlap, the gene regulation was mostly counter-expressed in placenta under chorioamnionitis (n=13/18, 72.22%; odds ratio [OR] upper bounds [≤]0.21) but co-expressed in late-secretory endometrium (n=3/9, 66.67%; OR lower bounds [≥]1.17). Neither the placental DEGs at first-nor second-trimester under normotensive pregnancy significantly overlapped with those under late-onset, severe PE without FGR. ConclusionsWe identified the transcriptome of endometrial maturation in placental dysfunction that distinguished early- and late-onset PE, and indicated chorioamnionitis as a PE competing risk. This study implied a feasibility to develop and validate the pathogenesis models that include pre-pregnancy and competing risks to decide if it is needed to collect prospective data for PE starting from pre-pregnancy including chorioamnionitis information.

bioinformatics↗