Inferring and modeling inheritance of differentially methylated changes across multiple generations.
Nucleic Acids Res
; 46(14): e85, 2018 08 21.
Article
em En
| MEDLINE
| ID: mdl-29750268
ABSTRACT
High-throughput methylation sequencing enables genome-wide detection of differentially methylated sites (DMS) or regions (DMR). Increasing evidence suggests that treatment-induced DMS can be transmitted across generations, but the analysis of induced methylation changes across multiple generations is complicated by the lack of sound statistical methods to evaluate significance levels. Due to software design, DMS detection was usually made on each generation separately, thus disregarding stochastic effects expected when a large number of DMS is detected in each generation. Here, we present a novel method based on Monte Carlo sampling, methylInheritance, to evaluate that the number of conserved DMS between several generations is associated to an effect inherited from a treatment and not randomness. Moreover, we developed an inheritance simulation package, methInheritSim, to demonstrate the performance of the methylInheritance method and to evaluate the power of different experimental designs. Finally, we applied methylInheritance to a DNA methylation dataset obtained from early-life persistent organic pollutants (POPs) exposed Sprague-Dawley female rats and their descendants through a paternal transmission. The results show that metylInheritance can efficiently identify treatment-induced inherited methylation changes. Specifically, we identified two intergenerationally conserved DMS at transcription start site (TSS); one of those persisted transgenerationally. Three transgenerationally conserved DMR were found at intra or integenic regions.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Metilação de DNA
/
Padrões de Herança
Tipo de estudo:
Health_economic_evaluation
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article