armDNA: A functional beta model for detecting age-related genomewide DNA methylation marks.
DNA methylation has been shown to play an important role in many complex diseases. The rapid development of high-throughput DNA methylation scan technologies provides great opportunities for genomewide DNA methylation-disease association studies. As methylation is a dynamic process involving time, it is quite plausible that age contributes to its variation to a large extent. Therefore, in analyzing genomewide DNA methylation data, it is important to identify age-related DNA methylation marks and delineate their functional relationship. This helps us to better understand the underlying biological mechanism and facilitate early diagnosis and prognosis analysis of complex diseases. We develop a functional beta model for analyzing DNA methylation data and detecting age-related DNA methylation marks on the whole genome by naturally taking sampling scheme into account and accommodating flexible age-methylation dynamics. We focus on DNA methylation data obtained through the widely used bisulfite conversion technique and propose to use a beta model to relate the DNA methylation level to the age. Adjusting for certain confounders, the functional age effect is left completely unspecified, offering great flexibility and allowing extra data dynamics. An efficient algorithm is developed for estimating unknown parameters, and the Wald test is used to detect age-related DNA methylation marks. Simulation studies and several real data applications were provided to demonstrate the performance of the proposed method.
['Wang|Chenyang|C|', 'Shen|Qi|Q|', 'Du|Li|L|', 'Xu|Jinfeng|J|', 'Zhang|Hong|H|']
D000293:Adolescent D000328:Adult D000367:Age Factors D000368:Aged D000369:Aged, 80 and over D000465:Algorithms D019175:DNA Methylation D005260:Female D015894:Genome, Human D059014:High-Throughput Nucleotide Sequencing D006801:Humans D008297:Male D008875:Middle Aged D012044:Regression Analysis D055815:Young Adult
Age-related DNA methylation bisulfite conversion beta regression microarray nonparametric transformation