2021/01/18 by Kaiqiong Zhao, Zhao, Kaiqiong, Karim Oualkacha +15
Biochemistry, Genetics and Molecular Biology · Computer Science · #Applications (stat.AP) #Bayesian Methods and Mixture Models #Epigenetics and DNA Methylation #FOS: Computer and information sciences #Methodology (stat.ME) #RNA modifications and cancer
paper · pdf · doi:10.48550/arxiv.2101.07374
openalex publication_date 2021/01/18 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
Identifying disease-associated changes in DNA methylation can help to gain a better understanding of disease etiology. Bisulfite sequencing technology allows the generation of methylation profiles at single base of DNA. We previously developed a method for estimating smooth covariate effects and identifying differentially methylated regions (DMRs) from bisulfite sequencing data, which copes with experimental errors and variable read depths; this method utilizes the binomial distribution to characterize the variability in the methylated counts. However, bisulfite sequencing data frequently include low-count integers and can exhibit over or under dispersion relative to the binomial distribution. We present a substantial improvement to our previous work by proposing a quasi-likelihood-based regional testing approach which accounts for multiplicative and additive sources of dispersion. We demonstrate the theoretical properties of the resulting tests, as well as their marginal and conditional interpretations. Simulations show that the proposed method provides correct inference for smooth covariate effects and captures the major methylation patterns with excellent power.