Bio-statistical approaches to evaluate the link between specific nutrients and methylation patterns in a breast cancer case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Abstract : Epigenetics data are challenging sets characterized by hundreds of thousands of features. The main objective of this thesis was to evaluate the performance of some of the existing statistical methods to handle sets of large dimension data, exploring the association between dietary factors related to breast cancer (BC) and DNA methylation within the EPIC study.In order to investigate the characteristics of epigenetics data, the identification of random and systematic sources of variability of methylation measurements was attempted, via the principal component partial R-square (PC-PR2) method. Using this technique, the performance of three popular normalization techniques to correct for unwanted sources of variability was evaluated by quantifying epigenetics variability attributed to laboratory factors before and after the application of each correction method.Once a suitable normalization procedure was identified, the association between alcohol intake, dietary folate and methylation levels was examined by means of three approaches: an analysis of individual CpG sites, of differentially methylated regions (DMRs) and using fused lasso regression. The last two methods aim at the identification of specific regions of the epigenome using the potential correlation between neighboring CpG sites. Global methylation levels were used to investigate the relationship between methylation and BC risk.By performing an exhaustive evaluation of the statistical tools used to disclose complexity of DNA methylation data, this thesis provides informative insights for studies focusing on epigenetics, with promising potentials to apply similar methodology to the analysis of other -omics data
Document type :
Theses
Complete list of metadatas

Cited literature [95 references]  Display  Hide  Download

https://tel.archives-ouvertes.fr/tel-01979135
Contributor : Abes Star <>
Submitted on : Saturday, January 12, 2019 - 5:23:10 PM
Last modification on : Saturday, January 12, 2019 - 5:23:11 PM
Long-term archiving on : Saturday, April 13, 2019 - 12:53:32 PM

File

TH2018PERRIERFLAVIE.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-01979135, version 1

Collections

Citation

Flavie Perrier. Bio-statistical approaches to evaluate the link between specific nutrients and methylation patterns in a breast cancer case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Bioinformatics [q-bio.QM]. Université de Lyon, 2018. English. ⟨NNT : 2018LYSE1146⟩. ⟨tel-01979135⟩

Share

Metrics

Record views

221

Files downloads

40