Epigenome-Wide Cross-Tissue Predictive Modeling and Comparison of Cord Blood and Placental Methylation in a Birth Cohort

Abstract

Aim: We compared predictive modeling approaches to estimate placental methylation using cord blood methylation. Materials & methods: We performed locus-specific methylation prediction using both linear regression and support vector machine models with 174 matched pairs of 450k arrays. Results: At most CpG sites, both approaches gave poor predictions in spite of a misleading improvement in array-wide correlation. CpG islands and gene promoters, but not enhancers, were the genomic contexts where the correlation between measured and predicted placental methylation levels achieved higher values. We provide a list of 714 sites where both models achieved an R² ≥0.75. Conclusion: The present study indicates the need for caution in interpreting cross-tissue predictions. Few methylation sites can be predicted between cord blood and placenta.

Keywords::

• 450k arrays
• cord blood
• DNA methylation
• epigenetics
• methylation prediction
• placenta
• support vector machine

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/3dp-2022-0019

Acknowledgements

The authors thank Alison Brown at the Partners HealthCare Center for Personalized Genetic Medicine Genotyping Facility for running the Illumina Arrays.

Financial & competing interests disclosure

This research was supported by NIH grants R01 HL095606, R01 HL114396, P30 ES023515, R01 ES021357 and R01 NR013945. AC Just was supported by grant R00 ES023450. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This research was supported by National Institutes of Health NIH grants R01 HL095606, R01 HL114396, P30 ES023515, R01 ES021357 and R01 NR013945. AC Just was supported by grant R00 ES023450. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.