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Permutation-based s...
Permutation-based significance analysis reduces the type 1 error rate in bisulfite sequencing data analysis of human umbilical cord blood samples
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- Laajala, Essi (författare)
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku Finland; Turku Doctoral Programme of Molecular Medicine, University of Turku, Turku, Finland; Department of Computer Science, Aalto University, Espoo, Finland
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- Halla-Aho, Viivi (författare)
- Department of Computer Science, Aalto University, Espoo, Finland
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- Grönroos, Toni (författare)
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku Finland
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- Kalim, Ubaid Ullah (författare)
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku Finland
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- Vähä-Mäkilä, Mari (författare)
- Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland
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- Nurmio, Mirja (författare)
- Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland
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- Kallionpää, Henna (författare)
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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- Lietzén, Niina (författare)
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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- Mykkänen, Juha (författare)
- Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland
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- Rasool, Omid (författare)
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku Finland
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- Toppari, Jorma (författare)
- Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland; Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland; Department of Pediatrics, Turku University Hospital, Turku, Finland
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- Oresic, Matej, 1967- (författare)
- Örebro universitet,Institutionen för medicinska vetenskaper,Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku Finland
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- Knip, Mikael (författare)
- Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Center for Child Health Research, Tampere University Hospital, Tampere, Finland
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- Lund, Riikka (författare)
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
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- Lahesmaa, Riitta (författare)
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku Finland; Institute of Biomedicine, University of Turku, Turku, Finland
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- Lähdesmäki, Harri (författare)
- Department of Computer Science, Aalto University, Espoo, Finland
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(creator_code:org_t)
- 2022-03-04
- 2022
- Engelska.
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Ingår i: Epigenetics. - : Taylor & Francis. - 1559-2294 .- 1559-2308. ; 17:12, s. 1608-1627
- Relaterad länk:
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https://doi.org/10.1...
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https://www.tandfonl...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- DNA methylation patterns are largely established in-utero and might mediate the impacts of in-utero conditions on later health outcomes. Associations between perinatal DNA methylation marks and pregnancy-related variables, such as maternal age and gestational weight gain, have been earlier studied with methylation microarrays, which typically cover less than 2% of human CpG sites. To detect such associations outside these regions, we chose the bisulphite sequencing approach. We collected and curated clinical data on 200 newborn infants; whose umbilical cord blood samples were analysed with the reduced representation bisulphite sequencing (RRBS) method. A generalized linear mixed-effects model was fit for each high coverage CpG site, followed by spatial and multiple testing adjustment of P values to identify differentially methylated cytosines (DMCs) and regions (DMRs) associated with clinical variables, such as maternal age, mode of delivery, and birth weight. Type 1 error rate was then evaluated with a permutation analysis. We discovered a strong inflation of spatially adjusted P values through the permutation analysis, which we then applied for empirical type 1 error control. The inflation of P values was caused by a common method for spatial adjustment and DMR detection, implemented in tools comb-p and RADMeth. Based on empirically estimated significance thresholds, very little differential methylation was associated with any of the studied clinical variables, other than sex. With this analysis workflow, the sex-associated differentially methylated regions were highly reproducible across studies, technologies, and statistical models.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- DNA methylation
- RRBS
- analysis workflow
- bisulphite sequencing
- differential methylation
- pregnancy
- sex
- spatial correlation
- type 1 error
- umbilical cord blood
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Laajala, Essi
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Halla-Aho, Viivi
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Grönroos, Toni
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Kalim, Ubaid Ull ...
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Vähä-Mäkilä, Mar ...
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Nurmio, Mirja
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Kallionpää, Henn ...
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Lietzén, Niina
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Mykkänen, Juha
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Rasool, Omid
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Toppari, Jorma
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Oresic, Matej, 1 ...
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Knip, Mikael
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Lund, Riikka
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Lahesmaa, Riitta
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Lähdesmäki, Harr ...
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Medicinsk geneti ...
- Artiklar i publikationen
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Epigenetics
- Av lärosätet
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Örebro universitet