University of Oulu

Dieckmann, L., Cruceanu, C., Lahti-Pulkkinen, M. et al. Reliability of a novel approach for reference-based cell type estimation in human placental DNA methylation studies. Cell. Mol. Life Sci. 79, 115 (2022). https://doi.org/10.1007/s00018-021-04091-3

Reliability of a novel approach for reference-based cell type estimation in human placental DNA methylation studies

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Author: Dieckmann, Linda1,2; Cruceanu, Cristiana1; Lahti-Pulkkinen, Marius3,4,5;
Organizations: 1Department of Translational Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany
2International Max Planck Research School for Translational Psychiatry, Munich, Germany
3Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
4Finnish Institute for Health and Welfare, Helsinki, Finland
5Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK
6Institute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Human Genetics, Helsinki, Finland
7Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
8Department of Obstetrics and Gynecology, Faculty of Medicine and Health Technology, Center for Child, Adolescent and Maternal Health, Tampere University Hospital and University of Tampere, Tampere, Finland
9Children’s Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
10Department of Child and Adolescent Psychiatry, Erasmus MC, Sophia Children’s Hospital, Rotterdam, The Netherlands
11Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland
12Hyvinkää Hospital, Helsinki and Uusimaa Hospital District, Hyvinkää, Finland
13Department of Experimental Obstetrics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany
14Department of Obstetrics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany
15Department of General Practice, University of Helsinki, Helsinki, Finland
16Folkhälsan Research Center, Helsinki, Finland
17Department of Obstetrics and Gynaecology and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
18Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
19Faculty of Medicine, PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
20Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
21Institute of Medical Psychology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany
22Department of Pediatrics, Development, Health, and Disease Research Program, University of California, Irvine, CA, USA
23Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.4 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2022052338137
Language: English
Published: Springer Nature, 2022
Publish Date: 2022-05-23
Description:

Abstract

The placenta is a central organ during early development, influencing trajectories of health and disease. DNA methylation (DNAm) studies of human placenta improve our understanding of how its function relates to disease risk. However, DNAm studies can be biased by cell type heterogeneity, so it is essential to control for this in order to reduce confounding and increase precision. Computational cell type deconvolution approaches have proven to be very useful for this purpose. For human placenta, however, an assessment of the performance of these estimation methods is still lacking. Here, we examine the performance of a newly available reference-based cell type estimation approach and compare it to an often-used reference-free cell type estimation approach, namely RefFreeEWAS, in placental genome-wide DNAm samples taken at birth and from chorionic villus biopsies early in pregnancy using three independent studies comprising over 1000 samples. We found both reference-free and reference-based estimated cell type proportions to have predictive value for DNAm, however, reference-based cell type estimation outperformed reference-free estimation for the majority of data sets. Reference-based cell type estimations mirror previous histological knowledge on changes in cell type proportions through gestation. Further, CpGs whose variation in DNAm was largely explained by reference-based estimated cell type proportions were in the proximity of genes that are highly tissue-specific for placenta. This was not the case for reference-free estimated cell type proportions. We provide a list of these CpGs as a resource to help researchers to interpret results of existing studies and improve future DNAm studies of human placenta.

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Series: Cellular and molecular life sciences
ISSN: 1420-682X
ISSN-E: 1420-9071
ISSN-L: 1420-682X
Volume: 79
Article number: 115
DOI: 10.1007/s00018-021-04091-3
OADOI: https://oadoi.org/10.1007/s00018-021-04091-3
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Subjects:
Funding: Open Access funding enabled and organized by Projekt DEAL. The ITU study has been funded by the Academy of Finland (Award numbers: 1284859, 12848591, 312670 and 1324596) and the Finnish Diabetes Foundation. The PREDO Study has been funded by the Academy of Finland (JL: 311617 and 269925, KR: 1312670 ja 128789 1287891), EraNet Neuron, EVO (a special state subsidy for health science research), University of Helsinki Research Funds, the Signe and Ane Gyllenberg foundation, the Emil Aaltonen Foundation, the Finnish Medical Foundation, the Jane and Aatos Erkko Foundation, the Novo Nordisk Foundation, the Päivikki and Sakari Sohlberg Foundation, Juho Vainio foundation, Yrjö Jahnsson foundation, The Finnish Society of Sciences and Letters, Jalmari and Rauha Ahokas foundation, Sigrid Juselius Foundation granted to members of the Predo study board. ML-P receives funding from the Academy of Finland, University of Helsinki Funds. AP and TB disclose receipt of financial support for the research, authorship, and/or publication of this article, supported by DFG (BR2925/3-1,-2,-3 and PL241/8-2,-3). EK reports support from Academy of Finland, Foundation for Pediatric Research, Sigrid Juselius Foundation and Novo Nordisk Foundation.
Copyright information: © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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