Table 2 Summary of findings in the evaluation of PlaNET package epiphenotyping tools for genetic ancestry, gestational age, and placental cell type composition
From: The application of epiphenotyping approaches to DNA methylation array studies of the human placenta
PlaNET Epiphenotype variable | |||
|---|---|---|---|
Ancestry | Gestational age (refined-robust clock, RRPC) | Cell composition | |
Validation | PlaNET ancestry is highly correlated with independent SNP genotype-derived ancestry-informative markers (AIMs) | The refined-robust placenta clock (RRPC) is less accurate than clinically reported gestational age for term placentas, but predicts gestational age on average within 4 days | Cell composition results as expected for term chorionic villi: e.g., 70–90% total trophoblast; < 2% nucleated red blood cells |
Calculation considerations | PlaNET ancestry estimates are affected by normalization; data must be BMIQ + noob normalized prior to estimation [29] | Accuracy of placenta epigenetic clocks likely depends on data quality and uniformity of bulk tissue sampling | Recommended to estimate cell composition on BMIQ + noob normalized data [29] |
Epiphenotype variation by: | |||
Cohort of origin | QF2011 has predominant European ancestry, while V-NORM and V-SSRI are more diverse | Similar across cohorts | Altered trophoblast ratio in QF2011 cohort |
Processing time | No association | No association | Slight decrease in stromal cell composition at high processing times |
Sampling method | Not evaluated | Not evaluated | Yes, previously reported [15], though not able to be evaluated in the present similarly-sampled cohorts |
Sex | No association | No association | No association |
Ethnicity | Correlated with maternal ethnicity; but ancestry includes paternal contribution and is continuous not categorical | No association | Possibly higher ratio of cytotrophoblast: syncytiotrophoblast in placentas with Asian ancestry |
Reported gestational age | N/A | Accelerated epigenetic gestational age is reported in preeclampsia [18], though this work was conducted with an earlier placental epigenetic clock (not the RRPC) | Decrease in cytotrophoblast: syncytiotrophoblast ratio with increasing gestational age |
Cell composition | No association | Decrease in the ratio of cytotrophoblast:syncytiotrophoblast with increasing gestational age, but RRPC gestational age is robust to cell composition | N/A |