Maternal blood contamination of collected cord blood can be identified using DNA methylation at three CpGs

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dc.contributor.authorMorin, Alexander M
dc.contributor.authorGatev, Evan
dc.contributor.authorMcEwen, Lisa M
dc.contributor.authorMacIsaac, Julia L
dc.contributor.authorLin, David T S
dc.contributor.authorKoen, Nastassja
dc.contributor.authorCzamara, Darina
dc.contributor.authorRäikkönen, Katri
dc.contributor.authorZar, Heather J
dc.contributor.authorKoenen, Karestan
dc.contributor.authorStein, Dan J
dc.contributor.authorKobor, Michael S
dc.contributor.authorJones, Meaghan J
dc.date.accessioned2017-09-05T14:13:40Z
dc.date.available2017-09-05T14:13:40Z
dc.date.issued2017-07-25
dc.date.updated2017-08-06T03:32:44Z
dc.description.abstractBackground: Cord blood is a commonly used tissue in environmental, genetic, and epigenetic population studies due to its ready availability and potential to inform on a sensitive period of human development. However, the introduction of maternal blood during labor or cross-contamination during sample collection may complicate downstream analyses. After discovering maternal contamination of cord blood in a cohort study of 150 neonates using Illumina 450K DNA methylation (DNAm) data, we used a combination of linear regression and random forest machine learning to create a DNAm-based screening method. We identified a panel of DNAm sites that could discriminate between contaminated and non-contaminated samples, then designed pyrosequencing assays to pre-screen DNA prior to being assayed on an array. Results: Maternal contamination of cord blood was initially identified by unusual X chromosome DNA methylation patterns in 17 males. We utilized our DNAm panel to detect contaminated male samples and a proportional amount of female samples in the same cohort. We validated our DNAm screening method on an additional 189 sample cohort using both pyrosequencing and DNAm arrays, as well as 9 publically available cord blood 450K data sets. The rate of contamination varied from 0 to 10% within these studies, likely related to collection specific methods. Conclusions: Maternal blood can contaminate cord blood during sample collection at appreciable levels across multiple studies. We have identified a panel of markers that can be used to identify this contamination, either post hoc after DNAm arrays have been completed, or in advance using a targeted technique like pyrosequencing.
dc.identifier.apacitationMorin, A. M., Gatev, E., McEwen, L. M., MacIsaac, J. L., Lin, D. T. S., Koen, N., ... Jones, M. J. (2017). Maternal blood contamination of collected cord blood can be identified using DNA methylation at three CpGs. <i>Clinical Epigenetics</i>, http://hdl.handle.net/11427/25041en_ZA
dc.identifier.chicagocitationMorin, Alexander M, Evan Gatev, Lisa M McEwen, Julia L MacIsaac, David T S Lin, Nastassja Koen, Darina Czamara, et al "Maternal blood contamination of collected cord blood can be identified using DNA methylation at three CpGs." <i>Clinical Epigenetics</i> (2017) http://hdl.handle.net/11427/25041en_ZA
dc.identifier.citationMorin, A. M., Gatev, E., McEwen, L. M., MacIsaac, J. L., Lin, D. T., Koen, N., ... & Stein, D. J. (2017). Maternal blood contamination of collected cord blood can be identified using DNA methylation at three CpGs. Clinical epigenetics, 9(1), 75.
dc.identifier.ris TY - Journal Article AU - Morin, Alexander M AU - Gatev, Evan AU - McEwen, Lisa M AU - MacIsaac, Julia L AU - Lin, David T S AU - Koen, Nastassja AU - Czamara, Darina AU - Räikkönen, Katri AU - Zar, Heather J AU - Koenen, Karestan AU - Stein, Dan J AU - Kobor, Michael S AU - Jones, Meaghan J AB - Background: Cord blood is a commonly used tissue in environmental, genetic, and epigenetic population studies due to its ready availability and potential to inform on a sensitive period of human development. However, the introduction of maternal blood during labor or cross-contamination during sample collection may complicate downstream analyses. After discovering maternal contamination of cord blood in a cohort study of 150 neonates using Illumina 450K DNA methylation (DNAm) data, we used a combination of linear regression and random forest machine learning to create a DNAm-based screening method. We identified a panel of DNAm sites that could discriminate between contaminated and non-contaminated samples, then designed pyrosequencing assays to pre-screen DNA prior to being assayed on an array. Results: Maternal contamination of cord blood was initially identified by unusual X chromosome DNA methylation patterns in 17 males. We utilized our DNAm panel to detect contaminated male samples and a proportional amount of female samples in the same cohort. We validated our DNAm screening method on an additional 189 sample cohort using both pyrosequencing and DNAm arrays, as well as 9 publically available cord blood 450K data sets. The rate of contamination varied from 0 to 10% within these studies, likely related to collection specific methods. Conclusions: Maternal blood can contaminate cord blood during sample collection at appreciable levels across multiple studies. We have identified a panel of markers that can be used to identify this contamination, either post hoc after DNAm arrays have been completed, or in advance using a targeted technique like pyrosequencing. DA - 2017-07-25 DB - OpenUCT DO - 10.1186/s13148-017-0370-2 DP - University of Cape Town J1 - Clinical Epigenetics LK - https://open.uct.ac.za PB - University of Cape Town PY - 2017 T1 - Maternal blood contamination of collected cord blood can be identified using DNA methylation at three CpGs TI - Maternal blood contamination of collected cord blood can be identified using DNA methylation at three CpGs UR - http://hdl.handle.net/11427/25041 ER - en_ZA
dc.identifier.urihttp://dx.doi.org/10.1186/s13148-017-0370-2
dc.identifier.urihttp://hdl.handle.net/11427/25041
dc.identifier.vancouvercitationMorin AM, Gatev E, McEwen LM, MacIsaac JL, Lin DTS, Koen N, et al. Maternal blood contamination of collected cord blood can be identified using DNA methylation at three CpGs. Clinical Epigenetics. 2017; http://hdl.handle.net/11427/25041.en_ZA
dc.language.isoen
dc.publisherBioMed Central
dc.publisher.departmentDepartment of Paediatrics and Child Healthen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rights.holderThe Author(s).
dc.sourceClinical Epigenetics
dc.source.urihttps://clinicalepigeneticsjournal.biomedcentral.com/
dc.subject.otherCord blood
dc.subject.otherContamination
dc.subject.otherDNA methylation
dc.subject.other450K
dc.subject.otherGenotyping
dc.subject.otherMaternal blood
dc.subject.otherBlood banking
dc.titleMaternal blood contamination of collected cord blood can be identified using DNA methylation at three CpGs
dc.typeJournal Article
uct.type.filetypeText
uct.type.filetypeImage
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