Projekteja vuodessa
Abstrakti
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.
Alkuperäiskieli | Englanti |
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Sivut | 1608-1627 |
Sivumäärä | 20 |
Julkaisu | Epigenetics |
Vuosikerta | 17 |
Numero | 12 |
Varhainen verkossa julkaisun päivämäärä | 6 maalisk. 2022 |
DOI - pysyväislinkit | |
Tila | Julkaistu - 2022 |
OKM-julkaisutyyppi | A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä |
Sormenjälki
Sukella tutkimusaiheisiin 'Permutation-based significance analysis reduces the type 1 error rate in bisulfite sequencing data analysis of human umbilical cord blood samples'. Ne muodostavat yhdessä ainutlaatuisen sormenjäljen.Tietoaineistot
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Permutation-based significance analysis reduces the type 1 error rate in bisulfite sequencing data analysis of human umbilical cord blood samples
Laajala, E. (Creator), Halla-aho, V. (Creator), Grönroos, T. (Creator), Kalim, U. U. (Creator), Vähä-Mäkilä, M. (Creator), Nurmio, M. (Creator), Kallionpää, H. (Creator), Lietzén, N. (Creator), Mykkänen, J. (Creator), Rasool, O. (Creator), Toppari, J. (Creator), University, M. (Creator), Knip, M. (Creator), Lund, R. (Creator), Lahesmaa, R. (Creator) & Lähdesmäki, H. (Creator), figshare, 2022
DOI - pysyväislinkki: 10.6084/m9.figshare.19311109.v2, https://tandf.figshare.com/articles/dataset/Permutation-based_significance_analysis_reduces_the_type_1_error_rate_in_bisulfite_sequencing_data_analysis_of_human_umbilical_cord_blood_samples/19311109/1
Tietoaineisto: Dataset
Projektit
- 3 Päättynyt
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Heal-Art jatko: Immunoregulation and Therapeutic Precision in Rheumatoid Arthritis
Lähdesmäki, H. (Vastuullinen tutkija)
01/01/2021 → 31/12/2022
Projekti: RCF Academy Project targeted call
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Molekyylimekanismien analysointi yhden solun tasolla
Lähdesmäki, H. (Vastuullinen tutkija)
01/09/2017 → 31/08/2021
Projekti: Academy of Finland: Other research funding
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P4 Diabetes: Yksilöllistetty lääketiede tyypin 1 diabeteksen ennustamisessa ja estossa
Lähdesmäki, H. (Vastuullinen tutkija)
01/09/2015 → 31/08/2019
Projekti: Academy of Finland: Other research funding
Laitteet
Lehtileikkeet
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Research Data from University of Turku and Abo Akademi University Update Understanding of Data Analytics (Permutation-based significance analysis reduces the type 1 error rate in bisulphite sequencing data analysis of human umbilical cord blood ...)
05/10/2023
1 kohde/ Medianäkyvyys
Lehdistö/media: Esiintyminen mediassa