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

Autor: Dieckmann L; Department of Translational Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.; International Max Planck Research School for Translational Psychiatry, Munich, Germany., Cruceanu C; Department of Translational Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany., Lahti-Pulkkinen M; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Finnish Institute for Health and Welfare, Helsinki, Finland.; Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK., Lahti J; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Kvist T; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Laivuori H; Institute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Human Genetics, Helsinki, Finland.; Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.; Department 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., Sammallahti S; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Finnish Institute for Health and Welfare, Helsinki, Finland.; Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.; Department of Child and Adolescent Psychiatry, Erasmus MC, Sophia Children's Hospital, Rotterdam, The Netherlands., Villa PM; Department 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.; Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland.; Hyvinkää Hospital, Helsinki and Uusimaa Hospital District, Hyvinkää, Finland., Suomalainen-König S; Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland., Rancourt RC; Department of Experimental Obstetrics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany., Plagemann A; Department of Experimental Obstetrics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany., Henrich W; Department of Obstetrics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany., Eriksson JG; Department of General Practice, University of Helsinki, Helsinki, Finland.; Folkhälsan Research Center, Helsinki, Finland.; Department of Obstetrics and Gynaecology and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Kajantie E; Finnish Institute for Health and Welfare, Helsinki, Finland.; Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.; Faculty of Medicine, PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway., Entringer S; Institute of Medical Psychology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany.; Department of Pediatrics, Development, Health, and Disease Research Program, University of California, Irvine, CA, USA., Braun T; Department of Obstetrics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany. thorsten.braun@charite.de., Räikkönen K; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland. katri.raikkonen@helsinki.fi., Binder EB; Department of Translational Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA., Czamara D; Department of Translational Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany. darina@psych.mpg.de.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2022 Feb 03; Vol. 79 (2), pp. 115. Date of Electronic Publication: 2022 Feb 03.
DOI: 10.1007/s00018-021-04091-3
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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